Dana Farber Webchat: The Latest in Ovarian Cancer Treatment & Research

The latest developments in ovarian cancer treatment and research are addressed in the video below via a Dana-Farber Cancer Institute webchat that was conducted on September 16, 2014.

The Susan F. Smith Center for Women’s Cancers at the Dana-Farber Cancer Institute conducted a live video webchat panel with Ursula Matulonis, M.D., medical director of the Gynecologic Oncology Program, and gynecologic oncologists Panos Konstantinopoulos, M.D., Ph.D., and Susana Campos, M.D., MPH. The live webchat was held on September 16, 2014.

The general webchat topics addressed by the Dana-Farber doctors are listed below. For your convenience, we also provided the approximate video start time associated with each discussion topic. The entire video runs 49 minutes and 20 seconds.

  • Various types/subtypes of ovarian cancer and treatment differences. [1:40 minutes]
  • CA-125 and other ovarian cancer biomarkers. [5:10 minutes]
  • Areas of ongoing ovarian cancer research. [9:28 minutes]
  • Ovarian cancer treatment alternatives to standard of care chemotherapy. [13:55 minutes]
  • PARP Inhibitors & Immunotherapy. [15:03 minutes]
  • Mechanisms to reverse platinum drug resistance. [17:15 minutes]
  • Correlation between ovarian cancer and HPV (Human papillomavirus). [19:30 minutes]
  • The use of clinical trials for the treatment of ovarian cancer. [19:43 minutes]
  • Stage 1 ovarian cancer prognosis. [21:47 minutes]
  • Gene mutations related to hereditary ovarian cancer risk. [22:55 minutes]
  • Treatment options for platinum drug refractory/resistant ovarian cancer. [25:27 minutes]
  • Treatment of BRCA gene-mutated ovarian cancer patients. [27:50 minutes]
  • Ovarian cancer prevention. [30:18 minutes]
  • Promising treatments for ovarian clear cell cancer. [31:43 minutes]
  • Proper nutrition during and after ovarian cancer treatment. [33:47 minutes]
  • Symptoms associated with an ovarian cancer recurrence. [35:06 minutes]
  • Ovarian neuroendocrine cancer. [36:16 minutes]
  • Small-cell ovarian cancer. [39:22 minutes]
  • Origin of ovarian cancer. [42:41 minutes]
  • Treatment options for isolated or limited recurrent ovarian cancer tumors/lesions. [45:26 minutes]
  • Closing: Most Exciting Ovarian Cancer Developments. [47:07 minutes]

 

U.S. President Barack Obama Proclaims September 2014 As National Ovarian Cancer Awareness Month — What Should You Know?

Today, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. “This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.”

WhiteHouse-LogoToday, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will continue to honor the women who have lost their lives to the disease (including our own Elizabeth “Libby” Remick), support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

didyouknow

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2014, the American Cancer Society (ACS) estimates that there will be approximately 21,980 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,270 U.S. women will die from the disease, or about 39 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — each and every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

  • BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.
  • Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.
  • Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.
  • Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA-125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

  • Treatment includes surgery and usually chemotherapy.
  • Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.
  • In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.
  • Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.
  • For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.
  • For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.
  • Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).
  • New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.
  • Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.
  • The 10-year relative survival rate for all disease stages combined is only 38%.
  • Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word to “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

beatlogo_308x196B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 29, 2014

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

obama_signing

Ovarian cancer is the most deadly of all female reproductive system cancers. This year nearly 22,000 Americans will be diagnosed with this cancer, and more than 14,000 will die from it. The lives of mothers and daughters will be taken too soon, and the pain of this disease will touch too many families. During National Ovarian Cancer Awareness Month, we honor the loved ones we have lost to this disease and all those who battle it today, and we continue our work to improve care and raise awareness about ovarian cancer.

When ovarian cancer is found in its early stages, treatment is most effective and the chances for recovery are greatest. But ovarian cancer is difficult to detect early — there is no simple and reliable way to screen for this disease, symptoms are often not clear until later stages, and most women are diagnosed without being at high risk. That is why it is important for all women to pay attention to their bodies and know what is normal for them. Women who experience unexplained changes — including abdominal pain, pressure, and swelling — should talk with their health care provider. To learn more about the risk factors and symptoms of ovarian cancer, Americans can visit www.Cancer.gov.

Regular health checkups increase the chance of early detection, and the Affordable Care Act expands this critical care to millions of women. Insurance companies are now required to cover well-woman visits, which provide women an opportunity to talk with their health care provider, and insurers are prohibited from charging a copayment for this service.

For the thousands of women affected by ovarian cancer, the Affordable Care Act also prohibits insurance companies from denying coverage due to a pre-existing condition, such as cancer or a family history of cancer; prevents insurers from denying participation in an approved clinical trial for any life-threatening disease; and eliminates annual and lifetime dollar limits on coverage. And as we work to ease the burden of ovarian cancer for today’s patients, my Administration continues to invest in the critical research that will lead to earlier detection, improved care, and the medical breakthroughs of tomorrow.

Ovarian cancer and the hardship it brings have affected too many lives. This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2014 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

IN WITNESS WHEREOF, I have hereunto set my hand this twenty-ninth day of August, in the year of our Lord two thousand fourteen, and of the Independence of the United States of America the two hundred and thirty-ninth.

BARACK OBAMA

__________________________________________________________

Sources:

  • Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014 [PDF file].
  • Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 29, 2014.

U.S. President Barack Obama Proclaims September 2013 As National Ovarian Cancer Awareness Month — What Should You Know?

Yesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. “… During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer…. This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease. …”

WhiteHouse-LogoYesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will honor the women who have lost their lives to the disease, support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

didyouknow

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2013, the American Cancer Society (ACS) estimates that there will be approximately 22,240 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,030 U.S. women will die from the disease, or about 38 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

  • BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.
  • Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.
  • Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.
  • Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA-125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

  • Treatment includes surgery and usually chemotherapy.
  • Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.
  • In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.
  • Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.
  • For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.
  • For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.
  • Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).
  • New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.
  • Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.
  • The 10-year relative survival rate for all disease stages combined is only 38%.
  • Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word To “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

beatlogo_308x196B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 30, 2013

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

obama_signingEach September, America calls attention to a deadly disease that affects thousands of women across our country. This year, over 22,000 women will develop ovarian cancer, and more than half that number of women will die of this disease. During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer.

Because ovarian cancer often goes undetected until advanced stages, increasing awareness of risk factors is critical to fighting this disease. Chances of developing ovarian cancer are greater in women who are middle-aged or older, women with a family history of breast or ovarian cancer, and those who have had certain types of cancer in the past. I encourage all women, especially those at increased risk, to talk to their doctors. For more information, visit www.Cancer.gov.

My Administration is investing in research to improve our understanding of ovarian cancer and develop better methods for diagnosis and treatment. As we continue to implement the Affordable Care Act, women with ovarian cancer will receive increased access to health care options, protections, and benefits. Thanks to this law, insurance companies can no longer set lifetime dollar limits on coverage or cancel coverage because of errors on paperwork. By 2014, the health care law will ban insurers from setting restrictive annual caps on benefits and from charging women higher rates simply because of their gender. Additionally, insurance companies will be prohibited from denying coverage or charging higher premiums to patients with pre-existing conditions, including ovarian cancer.

This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2013 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

IN WITNESS WHEREOF, I have hereunto set my hand this thirtieth day of August, in the year of our Lord two thousand thirteen, and of the Independence of the United States of America the two hundred and thirty-eighth.

BARACK OBAMA

__________________________________________________________

Sources:

  • Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013 [PDF file].
  • Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 30, 2013.

PARP Inhibitor Olaparib Has Activity in High-Grade Serous Ovarian Cancer Without Inherited BRCA1 or BRCA2 Gene Mutations

Researchers affiliated with the British Columbia Cancer Agency reported Phase 2 clinical study results indicating that advanced ovarian cancer, with and without germline (inherited) BRCA 1 or BRCA 2 gene mutations, responded to treatment with the PARP inhibitor olaparib. The Phase 2 study results were published online in the August 21 edition of The Lancet Oncology.

Karen A. Gelmon, M.D., Lead Study Author, Medical Oncologist, and Head of the Investigational Drug Program, Experimental Therapeutics, Department of Medical Oncology, British Columbia Cancer Agency

Researchers affiliated with the British Columbia Cancer Agency reported results from a Phase 2 clinical study indicating that advanced ovarian cancer, with and without germline (inherited) BRCA 1 or BRCA 2 gene mutations, responded to treatment with the PARP (poly(ADP-ribose) polymerase ) inhibitor olaparib (a/k/a AZD2281).[1] The Phase 2 study results were published online in the August 21 edition of the Lancet Oncology.

Preliminary findings from this study were reported at the 2011 American Society of Clinical Oncology annual meeting, which was held in Chicago earlier this year. [2]

The Phase 2 study results indicate that approximately 41% of women with BRCA1 or BRCA 2-mutated ovarian cancer had objective responses to the targeted agent, along with 24% of patients with non-BRCA gene mutated ovarian cancer. The findings suggest that the PARP inhibitor olaparib might have broad applicability in ovarian cancer.

Unfortunately, the drug olaparib failed to produce any objective responses in patients with non-BRCA gene mutated, triple negative breast cancer. Triple negative breast cancer is a difficult to treat subtype of the disease that lacks three of the cellular “receptors” known to fuel most breast cancers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2).

Background

Olaparib is a small-molecule, potent oral PARP inhibitor. Olaparib targets PARP, an enzyme essential for repair of single-strand DNA breaks. Preclinical evidence showed that the drug olaparib had activity against tumors with homologous recombination (HR) DNA repair defects, such as those caused by BRCA 1 or BRCA 2 gene mutations.

Germline (inherited) BRCA 1 or BRCA 2 gene mutations confer a high risk of breast and ovarian cancers, and tumors arising from the mutations have aggressive tendencies, such as triple-negative breast cancer. PARP inhibition has already demonstrated activity in cancers with germline mutations. Accordingly, the goal of the Canadian researchers was to assess the safety and tolerability of this drug in patients with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer, which did not possess BRCA1 or BRCA2 mutations.

Past study reporting associated with olaparib over the past twelve months has been somewhat mixed. Data reported at the 2010 European Society of Medical Oncology annual congress showed no significant effect of olaparib on progression-free survival (PFS) in women with advanced BRCA gene-mutated ovarian cancer. [3] In contrast, data presented at the 2011 American Society of Clinical Oncology meeting showed almost a doubling of PFS with olaparib among women with relapsed, platinum-sensitive ovarian cancer. [4]

Olaparib Phase 2 Study Design

The olaparib Phase 2 study enrolled women into 4 cohorts or trial arms. The two stage trial design included:

  • BRCA 1 or BRCA 2 gene mutation negative (or unknown mutation status) patients with high-grade serous, undifferentiated, fallopian-tube, or primary peritoneal cancer (Arm A) or triple-negative breast cancer (Arm B); and
  • Two reference groups with recurrent ovarian cancer (Arm C) or breast cancer (Arm D) who possessed BRCA 1 or BRCA 2 gene mutations.

All patients had tumor biopsies taken prior to treatment, after 2 cycles of treatment, and at disease progression to assess PARP inhibitor activity, loss of heterozygosity, gene mutational changes, BRCA 1 or BRCA 2 gene expression, and other markers of response. Computed tomography (CT)/magnetic ressonance imaging (MRI) assessments were performed prior to treatment and at every 2 treatment cycles. The patients were treated with single agent olaparib (400 mg twice a day) on a continuous basis in 4 week cycles.

Researchers at six centers in Canada enrolled 91 patients in this Phase 2, open-label, nonrandomized trial (ClinicalTrials.gov ID: NCT00679783). [5] Eligible patients had advanced metastatic or recurrent breast cancer, or advanced ovarian cancer.

The study population consisted of 65 patients with ovarian cancer and 26 patients with breast cancer. All of the breast cancer patients and 64 ovarian cancer patients received at least one dose of olaparib (400 mg twice a day) and were included in the final study analysis.

The ovarian cancer cohort consisted of 17 patients with BRCA gene mutations and 47 patients without BRCA gene mutations. The breast cancer cohort consisted of 10 patients with BRCA gene mutations and 16 patients without BRCA gene mutations.

The researchers reported that 58 patients with ovarian cancer had the serous subtype (13 patients with BRCA gene mutations, 45 patients without BRCA gene mutations). In the breast cancer cohort, 21 patients had triple-negative disease, including five patients with BRCA gene mutations.

The primary endpoint of the Phase 2 study was objective response, as determined by RECIST (Response Evaluation Criteria In Solid Tumors) criteria.

Olaparib Phase 2 Study Results

None of the breast cancer patients had objective responses, and the disease control rate (proportion of patients with complete responsepartial response, or stable disease) at eight weeks was 38% (10 of 26 patients).

In the ovarian cancer cohort, seven of 17 (41%) patients with BRCA gene mutations, and 11 of 46 (24%) patients without BRCA gene mutations, experienced objective responses. The overall disease control rate was 66% (42 of 64), including benefit in 76% (11 of 17) of BRCA-negative patients and 62% (29 of 47) of the BRCA-positive subgroup.

The researchers reported: “Although responses were seen in both platinum-sensitive and platinum-resistant populations, our post hoc analysis reported activity mostly in patients with platinum-sensitive disease.” As a precaution, the researchers noted that their findings should be interpreted conservatively because of the small study sample size.

Among the ovarian cancer patients, there were thirteen premature discontinuations, without confirmed radiological disease progression. Six patients dropped out of the Phase 2 olaparib study. Of those patients, three women dropped out because of worsening disease, and three more women dropped out because of adverse events. One patient in the breast cancer group discontinued early because of an adverse event.

The most common adverse events in ovarian and breast cancer patients were fatigue (58 patients), nausea (58), vomiting (34), and decreased appetite (30).

“To our knowledge, this study is the first to show that olaparib monotherapy has activity in women with pretreated high-grade serous ovarian cancer without germline BRCA1 or BRCA2 mutations,” said Karen A. Gelmon, M.D., lead study author, medical oncologist, and head of the Investigational Drug Program, Experimental Therapeutics, within the department of medical oncology of the British Columbia Cancer Agency, along with her co-authors. Dr. Gelmon is also a professor of  medicine at the University of British Columbia.

“New treatments targeting DNA repair mechanisms seem to provide new hope for treatment of ovarian cancer,” the Canadian researchers added. “Subsequent reports of this study assessing tumor biopsies might identify which patients obtain most clinical benefit from olaparib.”

Expert Commentary

Melinda Telli, M.D., Assistant Professor, Stanford School of Medicine, Stanford University

The study findings by Gelmon et al. were accompanied by a commentary which was written by Melinda L. Telli, M.D., assistant professor, Stanford School of Medicine. [6] In that commentary, Dr. Telli states:

… Their [Gelson et al.] study is noteworthy in that it shows, for the first time, activity of a PARP inhibitor as monotherapy in women with advanced high-grade serous ovarian cancer who do not have a germline BRCA1 or BRCA2 mutation. This finding not only suggests new therapeutic possibilities for women with this aggressive type of ovarian cancer, but also importantly confirms the hypothesis that subpopulations of patients with common sporadic tumors can be targeted effectively with PARP inhibitor therapy. An additional important negative finding of this study was the absence of objective responses to single-agent olaparib in women with sporadic triple-negative breast cancer, although the numbers were small and patients heavily pretreated. With new therapies come new challenges, and the clinical development of PARP inhibitors has certainly encountered many obstacles. Thus, to see the potential of these drugs realized is particularly satisfying. This important finding of activity in high-grade serous ovarian cancer marks a new beginning to what will hopefully be a long and fruitful future for PARP inhibitors as they make their move beyond BRCA.

Another expert expressed excitement about the future potential of olaparib. Stephanie V. Blank, M.D., an assistant professor in clinical gynecologic oncology at NYU School of Medicine, said:

It is extremely exciting that an agent as promising as olaparib can be effective in a broader group of women than had been expected. The next challenge will lie in getting our hands on the drug, which at present is only available for patients on clinical trials.

Study Relationship Disclosures

The study was supported by AstraZeneca. Gelmon and several co-authors disclosed relationships with AstraZeneca. The co-authors included AstraZeneca employees. Dr. Telli reported no relevant disclosures.

Libby’s H*O*P*E* Commentary

We would like to extend our congratulations to Dr. Gelmon, as well as her co-investigators, many of whom are critical team members of  the Ovarian Cancer Research Program of British Columbia (OvCaRe). On September 8, 2010, we reported on the OvCaRe team finding of prevalent ARID1A gene mutations in endometriosis-associated, epithelial ovarian cancers (i.e., clear cell and endometrioid). [7]

The findings reported by Gelmon et al. will take on critical importance if it is eventually proven that PARP inhibitors could benefit up to 50% of high-grade serous ovarian cancer patients who possess germline (inherited) or somatic (lifetime acquired) mutations in the BRCA 1 or BRCA 2 gene, or other alternations in the HR DNA repair pathway, as suggested by past preclinical study findings, [8] including those recently reported by The Cancer Genome Atlas. [9]

References

1/ Gelmon KA, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: A phase II, multicenter, open-label, nonrandomized study. Lancet Oncol 2011; 12: 852-861. [Abstract]

2/Gelmon KA, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol 28:15s, 2010 (suppl; abstr 3002) [2011 American Society of Clinical Oncology Annual Meeting, Abstract 3002]

3/Kaye S, et al Phase II study of the oral PARP inhibitor olaparib (AZD2281) versus liposomal doxorubicin in ovarian cancer patients with BRCA1 and/or BRCA2 mutations. Annals of Oncology 2010 21(8)8): viii304–viii313, 2010 doi:10.1093/annonc/mdq526 [2010 European Society of Medical Oncology Annual Meeting, Abstract 9710, Adobe Reader PDF Document].

4/Ledermann JA, et al. Phase II randomized placebo-controlled study of olaparib (AZD2281) in patients with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol 29: 2011 (suppl; abstr 5003) [2011 American Society of Clinical Oncology Annual Meeting, Abstract 5003]

5/Phase II, Open Label, Non-Randomized Study of AZD2281 in the Treatment of Patients With Known BRCA or Recurrent High Grade Serous/ Undifferentiated Tubo-Ovarian Carcinoma and in Known BRCA or Triple Negative Breast Cancer to Determine Response Rate and Correlative Markers of Response, ClinicalTrials.gov ID: NCT00679783.

6/Telli ML. PARP inhibitors in cancer: Moving beyond BRCA. Lancet Oncol 2011; 12: 827-828. [Full Text]

7/British Columbian Researchers Make Groundbreaking Genetic Discovery In Endometriosis-Associated Ovarian Cancers, by Paul Cacciatore, Libby’s H*O*P*E*™, September 8, 2010.

8/New Assay Test Predicts That 50% of Ovarian Cancers Will Respond To In Vitro PARP Inhibition, by Paul Cacciatore, Libby’s H*O*P*E*™, November 11, 2010.

9/In-Depth Review: The Cancer Genome Atlas Reports On Landmark Analysis of High-Grade Serous Ovarian Cancer, by Paul Cacciatore, Libby’s H*O*P*E*™, August 5, 2011.

Additional Sources:

PARP Inhibitor Clinical Trial Information

Related Libby’s H*O*P*E* Posts

  • Inherited Mutations in RAD51D Gene Confer Susceptibility to Ovarian Cancer, August 7, 2011.
  • In-Depth Review: The Cancer Genome Atlas Reports On Landmark Analysis of High-Grade Serous Ovarian Cancer, August 5, 2011.
  • ASCO 2011: Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer, May 19, 2011.
  • PARP Inhibitor MK-4827 Shows Anti-Tumor Activity in First Human Clinical Study, November 17, 2010.
  • New Assay Test Predicts That 50% of Ovarian Cancers Will Respond To In Vitro PARP Inhibition, November 11, 2010.
  • PARP Inhibitor Olaparib Benefits Women With Inherited Ovarian Cancer Based Upon Platinum Drug Sensitivity, April 23, 2010.

Related WORD of HOPE Ovarian Cancer Podcast

  • 10 Exciting Ovarian Cancer Research Topics from 2010 — PARP Inhibitors & BRCA Gene-Mutated Ovarian Cancer (Topic #2 of 10), Episode #2, WORD of HOPE Ovarian Cancer Podcast, April 11, 2011.

U.K. Researchers Launch Clinical Trial of Mercaptopurine (6-MP) In Women with Hereditary Breast and Ovarian Cancer

A Cancer Research UK-funded clinical trial of a new drug for patients with advanced breast or ovarian cancer due to inherited BRCA gene mutations has been launched at the Experimental Cancer Medicine Centre at the University of Oxford.

A Cancer Research UK-funded trial of a new drug for patients with advanced breast or ovarian cancer due to inherited BRCA gene faults has been launched at the Experimental Cancer Medicine Centre at the University of Oxford (OxFord ECMC).

Mutations in the BRCA 1 (BReast CAncer-1) and BRCA 2 genes are thought to account for around 2-5 percent of all breast cancer cases. Women carrying the BRCA1 and BRCA2 mutation have a 45-65 percent chance of developing breast cancer, and a 20-45 percent chance of developing ovarian cancer, by the age of 70. Genetic testing for faulty BRCA genes is available for women with a very strong family history.

DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000 molecular lesions per cell per day. A special enzyme (shown above in color), encircles the double helix to repair a broken strand of DNA. Without molecules that can mend DNA single strand and double strand breaks, cells can malfunction, die, or become cancerous. (Photo: Courtesy of Tom Ellenberger, Washington University School of Medicine in St. Louis)

Cells lacking a properly functioning BRCA1 or BRCA2 gene  are less able to repair DNA damage. These defective cells are more sensitive to (i) platinum-based chemotherapy drugs such as cisplatin – which work by causing double-stranded DNA breaks, and (ii) PARP inhibitors, a newer class of drugs which prevent cells lacking a properly functioning BRCA gene from being able to repair damaged DNA. PARP inhibitors have shown promise in clinical trials but, as with most drugs, resistance can develop meaning some women can stop responding.

This trial, led by a team based at the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, is looking at a drug called “6MP” (a/k/a mercaptopurine; brand name: Purinethol), which is already used to treat leukemia and is often given in combination with another chemotherapy drug called “methotrexate.”

Earlier studies involving cells grown in the laboratory suggest that a class of drugs called “thiopurines,” which includes 6MP, are effective at killing cancer cells lacking BRCA – a gene which significantly increases the risk of breast and ovarian cancer – even after they have developed resistance to treatments like PARP inhibitors and cisplatin.

This trial is one of a growing number looking at matching patients to the most appropriate treatment based on their genetic makeup and that of their cancer – an approach known as “personalized medicine.”

If successful, the results will pave the way for a larger Phase 3 clinical trial, which could lead to an additional treatment option for the 15 out of every 100 women with breast and ovarian cancers, which are caused by faults in the BRCA1 or BRCA2 gene.

Trial leader Dr. Shibani Nicum, a gynecology specialist based at the Oxford ECMC, and a researcher in Oxford University’s Department of Oncology, said: “PARP inhibitors are a powerful new class of drugs developed specifically to target tumors caused by BRCA 1 and BRCA2 faults, but drug resistance remains a problem. We hope that the very encouraging results we have seen in early laboratory studies involving 6MP will lead to increased treatment options for these patients in the future.”

U.K. trial participant Suzanne Cole, 54, from Newbury, has a strong history of ovarian cancer in her family, with her sister, mother and grandmother all having been diagnosed with suspected cases of the disease at a relatively young age. But, it was not until many years later, after she herself was diagnosed with cancer, that doctors were able to trace the cause of this back to a BRCA1 mutation in her family.

Suzanne Cole said: “I was diagnosed in 2009 and initially had surgery then chemotherapy. I was then told about the trial and I went away and studied the information. The doctors were able to answer all my questions and then I agreed to sign up. I’m happy to be a part of this work as it could help others by moving treatments forward.”

Professor Mark Middleton, director of the Oxford ECMC, said: “It’s exciting to see drugs being developed for specific groups of patients who share the same underlying genetic faults in their cancer. Targeted treatments are at the cutting edge of cancer care and we’re proud to be involved in bringing such drugs a step closer to the clinic.”

Dr. Sally Burtles, Cancer Research UK’s director of the ECMC Network, said: “This study helps demonstrate the value of being able to pool subsets of patients who share specific rare faults in their tumor from a UK-wide network of Experimental Cancer Medicine Centres. This will be crucial as we move towards a new era of personalized medicine with treatments targeted according to the individual biological profile of a patient’s cancer.”

For more information on the trial, please visit www.cancerhelp.org.uk, or call the Cancer Research UK cancer information nurses on 0808-800-4040.

Sources:

  • Researchers trial new drug for women with hereditary breast and ovarian cancer, Press Release, Cancer Research UK, August 17, 2011.
  • Issaeva N, et al. 6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance. Cancer Res. 2010 Aug 1;70(15):6268-76. Epub 2010 Jul 14. PubMed PMID: 20631063; PubMed PMCID: PMC2913123.

2011 ASCO: Women with BRCA Gene Mutations Can Take Hormone-Replacement Therapy Safely After Ovary Removal

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania which will be presented on Monday, June 6 during the American Society for Clinical Oncology’s annual meeting. Results of the prospective study indicated that women with BRCA mutations who had their ovaries removed and took short-term HRT had a decrease in the risk of developing breast cancer.

Research has shown that in women who carry the BRCA gene mutations, the single most powerful risk-reduction strategy is to have their ovaries surgically removed by their mid-30s or early 40s. The decrease in cancer risk from ovary removal comes at the cost of early menopause and menopausal symptoms including hot flashes, mood swings, sleep disturbances and vaginal dryness — quality-of-life issues that may cause some women to delay or avoid the procedure.

Lead study author Susan M. Domchek, M.D., Associate Professor, Divison of Hematology-Oncology & Director, Cancer Risk Evaluation Program, Abramson Cancer Center, University of Pennsylvania

“Women with BRCA1/2 mutations should have their ovaries removed following child-bearing because this is the single best intervention to improve survival,” says lead author Susan M. Domchek, M.D., an associate professor in the division of Hematology-Oncology and director of the Cancer Risk Evaluation Program at Penn’s Abramson Cancer Center. “It is unfortunate to have women choose not to have this surgery because they are worried about menopausal symptoms and are told they can’t take HRT. Our data say that is not the case — these drugs do not increase their risk of breast cancer.”

Senior author Timothy R. Rebbeck, Ph.D., associate director of population science at the Abramson Cancer Center, notes that BRCA carriers may worry — based on other studies conducted in the general population showing a link between HRT and elevated cancer risk — that taking HRT may negate the effects of the surgery on their breast cancer risk. The message he hopes doctors will now give to women is clear: “If you need it, you can take short-term HRT. It doesn’t erase the effects of the oophorectomy.”

In the current study, Domchek, Rebbeck, and colleagues followed 795 women with BRCA1 mutations and 504 women with BRCA2 mutations who have not had cancer enrolled in the PROSE consortium database who underwent prophylactic oophorectomy, divided into groups of those who took HRT and those who did not. Women who underwent prophylactic oophorectomy had a lower risk of breast cancer than those who did not, with 14 percent of the women who took HRT after surgery developing breast cancer compared to 12 percent of the women who did not take HRT after surgery. The difference was not statistically significant.

Domchek says some of the confusion about the role of HRT in cancer risk elevation comes from the fact that the risks and benefits associated with HRT depend on the population of women studied. In this group of women — who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young — HRT should be discussed and considered an option for treating menopausal symptoms. “People want to make hormone replacement therapy evil, so they can say ‘Don’t do it,'” she says. “But there isn’t one simple answer. The devil is in the details of the studies.”

By contrast, Penn researchers and their collaborators in the PROSE consortium have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women, and reduces their mortality due to those cancers. But paying attention to the role that hormone depletion following preventive oophorectomy plays in women’s future health is also important.

“We know for sure that using HRT will mitigate menopausal symptoms, and we have pretty good evidence that it will help bone health,” she says. “Women need to be aware that going into very early menopause does increase their risk of bone problems and cardiovascular problems. And even if they aren’t going to take HRT, they need to be very attentive to monitoring for those issues. But they also need to know that HRT is an option for them and to discuss it with their doctors and other caregivers.”

About Penn Medicine

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.

About the University of Pennsylvania Perelman School of Medicine

Penn’s Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools and among the top 10 schools for primary care. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

About the University of Pennsylvania Health System

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Sources:

ASCO 2011: Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

A randomized phase II clinical trial showed that the oral PARP inhibitor drug olaparib (AZD2281), given after chemotherapy, improved progression-free survival in women with the most common type of recurrent ovarian cancer.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving maintenance therapy with the PARP (poly (ADP-ribose) polymerase) inhibitor olaparib were highlighted today in the ASCO press briefing, as summarized below.

Randomized Study Shows that Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

A phase II randomized trial showed that maintenance treatment with the oral PARP inhibitor drug olaparib (AZD2281) improved progression-free survival by about four months in women with the most common type of relapsed ovarian cancer. This is the first randomized trial to demonstrate a benefit for maintenance therapy for recurrent ovarian cancer, and the first randomized trial in ovarian cancer of a PARP inhibitor– a novel class of molecularly targeted drugs.

The results of this study, if confirmed in larger trials, could lead to a new treatment approach for recurrent ovarian cancer in which drugs like olaparib are given over a long period of time to prevent recurrences or prolong remissions. This somewhat novel approach, called maintenance therapy, has already proven useful in lung cancer. Standard treatment for ovarian cancer includes platinum-based chemotherapy. After this regimen, patients are observed until recurrence, and then treated with another course of chemotherapy. While some tumors respond well to chemotherapy, the regimens are too toxic for patients to take continuously, and clinical trials have not shown any benefit for extended courses of chemotherapy.

Jonathan A. Ledermann, M.D., Lead Author & Principal Investigator of PARP Maintenance Study; Professor, Medical Oncology, UCL Cancer Institute, University College London

“A well-tolerated antitumor agent that could be used for months or perhaps years as maintenance therapy after standard chemotherapy could be a big step forward and ultimately extend survival,” said lead author Jonathan A. Ledermann, M.D., principal investigator of the study and Professor of Medical Oncology at UCL Cancer Institute, University College London. “This study demonstrates proof of principle for the concept of maintenance therapy in ovarian cancer using a PARP inhibitor. Our progression-free survival difference was very impressive and better than we anticipated.”

The multicenter, international study randomized 265 women with high-grade serous ovarian cancer to either olaparib or placebo. Patients were enrolled in the trial within 8 weeks of having achieved either a complete or partial response to platinum-based treatment. PARP inhibitors have been shown to work better in patients whose tumors have responded to platinum.

In the study, the progression-free survival (PFS) – the amount of time during and after treatment in which the cancer does not return – was significantly longer in the group receiving olaparib than the placebo group, with a median of 8.4 months versus 4.8 months. At the time of data analysis, half the patients randomized to olaparib (68 patients) had not relapsed and were still receiving the drug, while only 16 percent (21 patients) remained on placebo – so overall survival data were not yet available for analysis.

Adverse events were more commonly reported in the group receiving olaparib than placebo, including nausea, fatigue, vomiting, and anemia, but the majority of these were not severe. Dose reductions to manage side effects were allowed in the study and were more prevalent in the olaparib group (23 percent) compared to the placebo group (7 percent).

Olaparib inhibits the enzyme poly (ADP-ribose) polymerase — abbreviated “PARP” — which is involved in DNA (deoxyribonucleic acid) repair. Up to half of women with high-grade serous ovarian cancer – the most common type of ovarian cancer – may have a DNA repair deficiency that makes them more susceptible to treatment with PARP inhibitors.

A number of PARP inhibitors are being studied in phase II and phase III clinical trials, as single agents and in combination with standard chemotherapies and radiation, in some types of breast and ovarian cancers believed to have DNA repair defects.

Sources:

PARP Clinical Trials:
Resources:
Related WORD of HOPE™ Ovarian Cancer Podcasts:
Related Libby’s H*O*P*E*™ Postings:
Related Libby’s H*O*P*E*™ Videos Re PARP Inhibitors