Wednesday, October 28, 2020

EMA Recommends Approval of Olaparib/Bevacizumab for Frontline Maintenance in HRD+ Advanced Ovarian Cancer

 This article is reprinted from OncLive

The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for olaparib as maintenance treatment in adult patients with advanced, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response after first-line platinum-based chemotherapy plus bevacizumab and whose disease has homologous recombination deficiency positivity defined by either a BRCA1/2 mutation and/or genomic instability.

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for olaparib (Lynparza) as maintenance treatment in adult patients with advanced, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response after first-line platinum-based chemotherapy plus bevacizumab (Avastin) and whose disease has homologous recombination deficiency (HRD) positivity defined by either a BRCA1/2 mutation and/or genomic instability.1

 The recommendation for approval was based on data from a biomarker subgroup analysis of the phase 3 PAOLA-1 trial (NCT02477644), which had been published in the New England Journal of Medicine.2 Results from the trial showed that the addition of olaparib to bevacizumab maintenance treatment resulted in a 67% reduction in the risk of disease progression or death (HR, 0.33; 95% CI, 0.25-0.45) in patients with HRD-positive tumors, including those that harbored a BRCA mutation.3 

In this subgroup, the median progression-free survival (PFS) with olaparib/bevacizumab was 37.2 months versus 17.7 months with bevacizumab alone. For those with HRD positivity who did not harbor a BRCAmutation, the median PFS with the olaparib combination was 28.1 months versus 16.6 months with bevacizumab alone (HR, 0.43; 95% CI, 0.28-0.66). 

“Half of all patients with advanced ovarian cancer have HRD-positive tumors. [Olaparib] together with bevacizumab has demonstrated a median PFS benefit of more than 3 years versus 17.7 months with bevacizumab alone, offering new hope for women in this setting,” José Baselga, MD, PhD, stated in a press release. “This recommendation is a vital step toward addressing a large and critical unmet need and could bring a new treatment option that significantly delays relapse in this difficult-to-treat disease.”

The double-blind, placebo-controlled, phase 3 PAOLA-1 trial enrolled patients with newly diagnosed, advanced, FIGO stage III to IV, high-grade, serous or endometrioid ovarian, fallopian tube, or peritoneal cancer who had achieved a complete response (CR) or partial response (PR) to frontline platinum-based chemotherapy and bevacizumab, irrespective of genetic biomarker status or outcome before surgery. 

Participants were randomized in a 2:1 fashion to received either olaparib/bevacizumab (n = 537) or bevacizumab/placebo (n = 269) for frontline maintenance treatment. Bevacizumab was given at a dose of 15 mg/kg every 3 weeks on day 1 of the treatment cycle. In the experimental arm, olaparib was administered at a dose of 300 mg twice daily.

The primary end point of the trial was investigator-assessed PFS, while key secondary end points included PFS2, overall survival, time until first subsequent therapy or death, and global health status–quality of life dimension of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.

With regard to safety, the most common toxicities reported in 20% or more patients in the investigational and control arms, respectively, included fatigue (53% vs 32%), nausea (53% vs 22%), hypertension (46% vs 60%), anemia (41% vs 10%), lymphopenia (24% vs 9%), vomiting (22% vs 11%), and arthralgia (22% vs 24%).

Updated results from the trial were presented during the 2020 ESMO Virtual Congress on response rates for patients with evidence of disease per RECIST criteria and/or CA-125 criteria at study entry. Here, the ORRs per RECIST criteria were 30% with olaparib/bevacizumab versus 25% with bevacizumab alone in the overall population.

When broken down by subgroup, those with BRCA mutations (n = 47) experienced ORRs of 64% with the combination versus 42% with bevacizumab alone; 53% versus 31%, respectively in those with HRD positivity including BRCA mutations (n = 81), 32% versus 21% for those with HRD positivity without BRCA mutations (n = 33), and 13% versus 15% in those with HRD negativity (n = 83). 

 Moreover, the CA-125 response rate in the overall population with olaparib/bevacizumab was 36% versus 29% with bevacizumab alone. When broken down by subgroup, the CA-125 response rates with the combination in BRCA-positive patients was 83% versus 60% with bevacizumab alone; 70% versus 63%, respectively in those with HRD positivity, 50% versus 67% in those with HRD positivity and BRCA negativity, and 20% versus 0% in those with HRD negativity. 

In May 2020, the FDA approved olaparib in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer who are in complete or partial response to frontline platinum-based chemotherapy based on findings from PAOLA-1. 

Previously, in December 2018, the FDA approved olaparib for use as a maintenance treatment in patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in CR or PR to frontline platinum-based chemotherapy based on data from the phase 3 SOLO-1 trial.  


  1. Lynparza (olaparib) recommended for approval in EU by CHMP as first-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer. News release. AstraZeneca and Merck. September 21, 2020. Accessed September 21, 2020.
  2. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361
  3. LYNPARZA (olaparib) approved by FDA as first-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer. News release. FDA. May 8, 2020. Accessed September 21, 2020.
  4. Colombo N, Gantzer J, Ataseven B, et al. Maintenance olaparib + bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: RECIST and/or CA-125 objective response rate in the phase III PAOLA-1 trial. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual. Abstract 812M0.














Saturday, October 24, 2020

Prestigious Award Given to Dana Farber to Study Treatment Resistance in OC

Dana-Farber/Harvard Cancer Center (DF/HCC) has been awarded a $12 million grant from the National Cancer Institute (NCI) to bring promising ovarian cancer research from the laboratory to clinical practice. The highly competitive Specialized Programs of Research Excellence (SPORE) grant will help fund three research studies on overcoming the problem of treatment resistance in ovarian cancer and enable DF/HCC- affiliated institutions to build on recent therapeutic advances in this disease. The principal investigators of the SPORE grant are Alan D’Andrea, MD, director of the Susan F. Smith Center for Women's Cancers at Dana-Farber Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber and David Spriggs, MD Director of Gynecologic Oncology Program at MGH Cancer Center. 

“Through the Ovarian Cancer SPORE of the DF/HCC, several of the most urgent questions in ovarian cancer therapy will be addressed,” said Alan D’Andrea, MD. “We are grateful to the National Cancer Institute for recognizing the combined expertise of the DF/HCC institutions and providing the resources to further advance the significant therapeutic progress made in this disease in recent years.”

Ovarian cancer is the most lethal gynecological malignancy in the United States, with less than half of newly diagnosed women surviving more than five years. Because no effective screening measures exist for ovarian cancer, the disease is often diagnosed in an advanced stage, when it is difficult to treat successfully.

The three research projects supported by DF/HCC Ovarian Cancer SPORE seek to translate scientists’ growing understanding of treatment resistance in ovarian cancer into new therapeutic approaches.

  • New classes of drugs known as PARP inhibitors, which hamper cells’ ability to repair damaged DNA, are increasingly used to treat women newly diagnosed with ovarian cancer as well as those whose disease has recurred following standard treatment. These agents have changed the standard of care for many women with ovarian cancer and represent a major advance in the treatment of the disease. However, many patients eventually develop resistance to PARP inhibitors. The first research project supported by the SPORE grant will include clinical trials of drug combinations designed to extend the  effectiveness of PARP inhibitors.

  • The SPORE funding will also support the development and study of a novel neoantigen vaccine trial for ovarian cancer patients. The personalized vaccine will be designed to recognize cancer-specific proteins, called neoantigens, that are present on an individual’s cancer cells but not on normal cells. Used in conjunction with immunotherapy drugs known as a checkpoint inhibitors, such a vaccine could “steer” the immune system to a direct assault on the cancer cells.

  • The third project will address patients with recurrent or drug-resistant high-grade serous ovarian cancer or low-grade serous cancer. The SPORE funds will support research into novel combinations, such as a BCL inhibitor and a MEK inhibitor, and will look for biomarkers of drug activity.

"Our focus will be on new ovarian cancer therapies for which laboratory research provides evidence of their effectiveness," said Ursula Matulonis, MD. "Physician-researchers across the DF/HCC institutions will work collaboratively to test and develop the next generation of agents that we can deliver to our patients and ultimately improve outcomes. This is a very important collaborative grant for us.”

Additional components of the SPORE in Ovarian Cancer include a Developmental Research Program (DRP) and a Career Enhancement Program (CEP) as well as four core facilities to support the research: Administrative, Pathology, Biostatistics, and Organoids, Model Systems, and Biomarkers. 

The Specialized Programs of Research Excellence is a cornerstone of the NCI’s efforts to promote collaborative, interdisciplinary translational cancer research. SPORE grants involve both basic and clinical/applied scientists working together and support projects that will result in new and diverse approaches to the prevention, early detection, diagnosis, and treatment of human cancers.

The DF/HCC SPORE in Ovarian Cancer includes DF/HCC researchers from the Dana-Farber Cancer Institute, Massachusetts General Hospital (MGH), Brigham and Women’s Hospital, Beth Israel Deaconess Hospital, and Harvard Medical School (HMS).


Thursday, October 22, 2020

Scholarships for Women Affected by OC


I just found out about this from an email from The Clearity Foundation about scholarships for women who have been financially impacted by ovarian cancer. After all, who hasn't been impacted? The scholarships are for $6,000 but only three will be awarded. :(  Still, here's the article for those interested......

The Make A Difference Scholarship, made possible by a partnership between The Clearity Foundation and Select Justice, is a scholarship that offers women and others who have been directly impacted by ovarian cancer a chance to have renewed opportunities and receive a financial reward that helps advance them in their next steps.

Through the Make A Difference Scholarship, Select Justice will award $6,000 for the 2021 academic year to three lucky recipients. This partnership with The Clearity Foundation not only offers hope to those impacted by ovarian cancer — but it also offers them exciting opportunities for a tomorrow that’s filled with promise.

Monday, October 12, 2020

New Agents and Immunotherapy In the Works for OC


OncLive recently published an article about a new treatment currently in clinical trials. Antibody drug conjugates (ADCs) work by targeting the cancer cell directly. Essentially, a toxic payload is attached to an antibody that seeks out a very specific molecule called Folate receptor alpha (FRa). This molecule is found in large numbers in ovarian epithelial cancers.

Immunotherapy, whether using a single or combination drug has had some mixed results and there are studies currently underway.

To read more about these newer treatment options and the clinical trials that are underway, follow this link.

Monday, October 5, 2020

2020 TTT Virtual Retreat: Personal Thoughts

What an incredible weekend we just had with our condensed, TTT virtual retreat! Sure, we understand that nothing beats being together at Camp Kieve but boy, this was one heck of a retreat filled with fun activities (juggling anyone?), self-facials, self-massages, art projects, yoga, music & movement, foot soaks and plenty of time to meet in our virtual "tea room" for more intimate conversations.

In addition, our social worker Barbara led us in great discussions whose topics were selected from participant suggestions. More than anything, the committee who planned this year's retreat was focused on doing everything possible to maintain the intimacy and strengthen the bonds that previous retreat goers so value. With that in mind, the retreat still limited the number of women who could attend despite it being virtual. In this way, large and small break-out sessions were manageable and allowed everyone to get the chance to participate and feel a part of the group.

 Each woman received an enormous bag full of items to be used for each session plus plenty of surprise gifts - hand knitted winter hats, note cards, snacks, etc. (really too numerous to name) and all the items needed to do our own facials led by the fantastic women from Elizabeth Grady in Boston who instructed us on how to apply all our different creams and toners. (Oh my god - what a delightful treat that was!)

As I reflect on this past weekend what is a standout for me is how this wonderful group of women easily and quickly embraced, listened to and supported each other. Having been diagnosed w/advanced OC 5 years ago (and still going strong), I can personally attest to how isolating it was to get the diagnosis. This is a terrible disease but I couldn't ask for a better group of women around me. As a veteran of the retreat, there is nothing more important and fulfilling than to embrace and support newly diagnosed women. We are in this together...


Saturday, October 3, 2020

Trying to Avoid Sugar? Try These Perfect Protein Energy Balls/"Brownie" Snacks


Again, a big shout-out to Christine C. for this recipe! Below, I've included a similar recipe that uses only 3 ingredients: raw almonds (can use other favorite nuts), majool dates and cacao powder.



·       1 1/2 cup almonds (or other nuts) I use peanuts

·       1 cup pitted medjool dates

·       1 tbsp coconut oil

·       1 tbsp cacao powder

·       1 tbsp protein powder 

·       1 tbsp chia seeds I use 2 tbsp


·       Blend nuts in a food processor.

·       Add remaining ingredients to the food processor and blend until you get a smooth mixture.

·       Roll into little balls and store in the fridge or freezer.


This can be doubled and stored in the freezer (I put them on wax paper in a pyrex container)

Here's a variation on this from the cookbook, "Deliciously Ella" by Ella Woodward 


2 cups of raw almonds (or cashews or peanuts or even assorted raw nuts)

20 pitted Mejool dates (I buy them w/pits and then take them out b/c I find that the pitted ones are drier. The more sticky they are, the better the mixture holds together.)

3 TB of cacao powder (not coco powder b/c of it contains sugar)


  • Blend nuts in a food processor
  • Add remaining ingredients and blend well
  • Spread into a rectangular, freezer proof dish, then place in the freezer for an hour. 

Cut into brownie-sized pieces and enjoy!

ps - I keep my "brownies" in the freezer  or the refrigerator rather store them at room temp.