Tuesday, March 30, 2021
Ovarian cancer: Current treatments and latest advances
Friday, March 26, 2021
Triple Combination Therapy Showing Promise for Platinum Resistant OC
A dostarlimab triplet combination showed promise in a phase 2 study for treatment of patients with platinum-resistant ovarian cancer, according to a presentation at the Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer.
Antitumor activity as well as tolerability were observed in patients with platinum-resistant ovarian cancer (PROC) treated in the phase 2 OPAL study (NCT03574779), which examined the triplet combination of dostarlimab plus niraparib (Zejula) and bevacizumab (Avastin), according to results presented at the Society of Gynecologic Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer.1
A total of 41 patients were enrolled in the trial to receive the regimen that included the investigational PD-1 inhibitor. Two patients did not undergo a baseline scan and were excluded from the response-evaluable population (n = 39). Findings from cohort A (NCT02715284) were presented at the SGO meeting.
Antitumor activity was assessed in the response-evaluable population. Patients were eligible if they had high-grade PROC, recurrent epithelial ovarian, fallopian tube, primary peritoneal cancer, or recurrent carcinosarcoma of the ovary. Patients had received 1 to 2 prior lines of anticancer therapy for ovarian cancer, but no prior therapy with anti–PD-1/PD-L1 or PARP inhibitors.
The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1 and secondary end points were progression-free survival (PFS), safety, and disease control rate (DCR). In addition, investigators conducted a post hoc analysis for biomarker genes including BRCA mutation (BRCAm), homologous recombination repair mutation (HRRm), and PD-L1 status using combined positive score (CPS ≥1%).
After undergoing screening for 21 days, patients received 500 mg of intravenous (IV) dostarlimab every 3 weeks for the first 4 doses, then 1000 mg every 6 weeks thereafter, with 15 mg/kg IV bevacizumab every 3 weeks up to 15 months and 300 mg or 200 mg of oral niraparib (determined by baseline weight and platelet count) once daily until discontinuation.
Median patient age was 66 years (range, 37-83) and ECOG performance score was 0 (46.3%) or 1 (53.7%). Eighteen (43.9%) patients had received prior bevacizumab. Biomarker analysis at baseline showed that 9.8% of patients had BRCAm, 82.9% of patients had BRCA wild-type disease (BRCAwt), and 7.3% had unknown BRCA status. HRR analysis revealed that 17.1% of patients had HRRm, 75.6% of patients had HRRwt, and 7.3% had unknown HRR status. The majority of patients (68.3%) had positive PD-L1 status.
“The objective response rate was 17.9% [90% CI, 8.7%-31.1%] with 7 partial responses and zero complete responses,” said lead author Joyce F. Liu, MD, MPH, associate chief and director of clinical research, Division of Gynecologic Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts. Response data required that patients with a best response of complete response or partial response undergo a confirmation scan ≥4 weeks after the first scan in which a response was observed.
“Additionally, 23 patients had stable disease as their best response and the overall disease control rate was 76.9% [90% CI, 63.2%-87.4%],” she said. ORR was consistent across most subgroups, but investigators noted that patients who received prior bevacizumab showed a lower, nonsignificant, response rate (6%).
When reviewing best percentage change from baseline by HRR and PD-L1 status, the investigators noted that no correlation between these biomarkers or activity was observed. Median PFS in the total population (n = 41) was 7.6 months (95% CI, 4.2-10.6).
Comparatively, a prior phase 1/2 trial (NCT02657889) evaluating niraparib and pembrolizumab (Keytruda) showed an ORR of 18% in patients with PROC or who were otherwise ineligible for further platinum-based therapies.2
Overall the safety profile for patients in cohort A was consistent with the prior experience for each individual drug, and 97.6% of patients reported at least 1 any-grade treatment-related adverse effect (TRAE). Specifically, the most common total reported any-grade TRAEs that occurred with an overall incidence of ≥10% were fatigue (61.0%), thrombocytopenia event (48.8%), and hypertension (43.9%). The most common grade 3 TRAEs with an incidence ≥5% were hypertension (22.0%) and thrombocytopenia event (22.0%).
No TRAEs resulted in death and 34.1% of patients discontinued at least 1 of the 3 study drugs because of a TRAE.
“Although multiple patients [14.6%] developed grade 3 or higher small bowel obstructions, all were assessed as not being related to study drug,” said Liu, who is also assistant professor of medicine at Harvard Medical School. “One patient did develop a grade 4 bowel perforation event that was assessed as related to bevacizumab,” she said.
Liu noted that the majority of patients enrolled had BRCAwt or HRRwt tumors, and that 43.9% of patients had platinum-resistant disease, both of which are predictive factors associated with lower responses to therapy. However, “there were no clear response trends based on biomarkers,” she said.
1. Liu JF, Gaillard S, Wahner Hendrickson AE, et al. An open-label phase II study of dostarlimab (TSR-042), bevacizumab (bev), and niraparib combination in patients (pts) with platinum-resistant ovarian cancer (PROC): Cohort A of the OPAL trial. Presented at: Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women's Cancer; March 19-25, 2021; Virtual Abstract 23.
2. Konstantinopoulos PA, Waggoner S, Vidal GA, et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma. JAMA Oncol. 2019;5(8):1141-1149. doi:10.1001/jamaoncol.2019.1048
Tuesday, March 23, 2021
One in Forty: The Jewish-Cancer Connection Webinar on March 24th
Upcoming Events – Oneinforty Webinar Series
March 24th, 6:30 pm EST
Knowledge is Empowering: Understanding the Jewish-Cancer Connection
Upcoming Events from Ovations for the Cure of Ovarian Cancer
Team Ovations Fundraising With Jimmy Fund Walk to Fight Cancer which will be held Oct.3, 2021, goes to directly support the research of Dr. Ursula Matulonis, whom many of our readers will know from Dana Farber.
If walking isn't quite your thing but you love golfing, join Ovations for their annual golf tournament scheduled for Sept. 17, 2021 at the Brookmeadow Country Club in Canton, MA.
To find out more about these events and the other great work that Ovations for the Cure is involved in, follow this link.
Friday, March 19, 2021
NOCC Wellness Retreat Registration is Open!
Whether you are a survivor, patient, caregiver, or loved one — join our teal community from around the world online for the NOCC Wellness Retreat on May 7th and 8th, 2021! Learn what's new in ovarian cancer, how to manage stress and anxiety, and connect with others in the ovarian cancer community to hear inspiring stories of bravery and courage.
For more information, follow this link.
Tuesday, March 16, 2021
Cancer and the Covid 19 Vaccine
Dana Farber hosted this presentation on Jan. 28, 2021. It was an open forum and the Q&A session covers questions related to safety, efficacy and availability.
Friday, March 12, 2021
Stowe Weekend of Hope Goes Virtual Again
More interactive events are promised by the organizers and folks who would like to attend are encouraged to sign up to receive alerts.
The dates for this year's retreat are April 30-May 2. There will be presentations by medical leaders in the field of cancer, opportunities to network and on-line workshops.
If you've never attended this event, it is wonderful - and yes, it's even better in person but given the caliber of speakers and the care that goes into the planning and activities, there will be something for everybody to enjoy.
You can find out more info by following this link to the Stowe Weekend of Hope webpage or by clicking on the link to their Facebook page.
Tuesday, March 9, 2021
Covid Vaccine Harder to Get in These States Even If You Have Cancer
Essentially, if you live in Maine, Colorado, Ohio, West Virginia, or Nebraska, you may have trouble getting the vaccine early.
In Maine, the roll-out of the vaccine has been changed and is now based on age rather than on health status. In other states, interestingly, cancer was not deemed a sufficient reason to move to the head of the line for vaccination.
To read the article in its entirety, follow this link.
Friday, March 5, 2021
Cancer and Covid-19 Vaccine
I hope that many of you have by now at least received your first dose of the Covid-19 vaccine. For those who are still wondering, this Q&A appeared in The American Society of Clinical Oncologists and was last updated on 2/1/2021.
On December 17, 2020, the American Society of Clinical Oncology and Infectious Diseases Society of America held a “COVID-19 Vaccine & Patients with Cancer” webinar to discuss the importance of COVID-19 vaccination and to provide expert opinion on its use for cancer patients. At the time of the webinar, there was only one vaccine authorized for use against COVID-19, the Pfizer/BioNTech vaccine, although the expert panel discussion focused on mRNA vaccines and addressed vaccines in general. The panel of oncology and infectious disease experts agreed that the Pfizer, and now Moderna, vaccines have been shown to be safe and effective for the general population and there was no evidence that they would not be safe for most cancer patients, although it should be noted that patients receiving immunosuppressive and cytotoxic treatments were excluded from participation in the vaccine trials to date so there is little to no data on the safety and efficacy of the Pfizer and Moderna vaccines in cancer patients.
Memorial Sloan Kettering Cancer Center has made available an interim guideline on vaccination for cancer patients. The National Comprehensive Cancer Network (NCCN) has made available preliminary recommendations as well. The recommendations in these documents are based on opinion and extrapolation from other vaccine studies and may change rapidly as new information becomes available.
Should people with cancer be vaccinated against COVID-19?
At this time, patients with cancer may be offered vaccination against COVID-19 as long as components of that vaccine are not contraindicated. The current CDC interim clinical guidance discusses immunocompromised individuals. It states: “Immunocompromised individuals may still receive COVID-19 vaccination if they have no contraindications to vaccination. However, they should be counseled about the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses and the need to continue to follow all current guidance to protect themselves against COVID-19.” The expert panel noted that while some immunocompromised patients may experience decreased response to the vaccine, it may still confer some benefit and is important to reduce the risk or severity of COVID-19 to cancer patients, especially given recent evidence of higher rates of severe infection.
Should people undergoing active treatment for cancer be vaccinated against COVID-19?
At this time, patients undergoing treatment may be offered vaccination against COVID-19 as long as any components of the vaccine are not contraindicated. Oncologists have experience providing other types of vaccines to patients receiving treatment for cancer, including chemotherapy, immunotherapy, radiation therapy or stem cell transplantation. Strategies such as providing the vaccine in between cycles of therapy and after appropriate waiting periods for patients receiving stem cell transplants and immune globulin treatment can be used to reduce the risks while maintaining the efficacy of vaccination.
Should cancer survivors be vaccinated against COVID-19?
Cancer survivors may be offered vaccination against COVID-19 as long as any components of the vaccine are not contraindicated.
Are there people who should not be vaccinated?
At this time, only those with contraindications to a specific vaccine component should not be offered vaccination with that specific product. These contraindications are described in detail in CDC interim clinical guidance.
What other concerns are there for people with cancer who are vaccinated?
As there is still uncertainty around the extent to which immunocompromised patients with cancer will develop immunity in response to vaccination, vaccinated patients should continue to follow current guidance to protect themselves from exposure to COVID-19. The expert panel underscored the message that while providing the vaccine to cancer patients and their caregivers will reduce risk for infection or clinical COVID-19 disease, they emphasized the importance of continuing practices of wearing masks, social distancing, and maintaining good hand hygiene even after vaccination.
CDC Advisory Committee on Immunization Practices
CDC’s Advisory Committee on Immunization Practices (ACIP) has approved several recommendations regarding the prioritization of COVID-19 vaccination. Once approved by the CDC, these recommendations are intended to help state and local jurisdictions maximize the distribution of the vaccines while they are still in scarce supply. These recommendations are not binding mandates, nor do they relate to the allocation of the vaccine itself which is being managed separately within HHS. To date, they have recommended the following priority groupings:
Phase 1a: The Advisory Committee on Immunization Practices (ACIP) recommended, as interim guidance, that both (1) health care personnel and (2) residents of long-term care facilities be offered COVID-19 vaccine in the initial phase of the vaccination program.
Phase 1b: persons aged ≥75 years and frontline essential workers. For purposes of this recommendation, the following essential workers are considered frontline: firefighters, police officers, corrections officers, food and agricultural workers, Postal Service workers, manufacturing workers, grocery store workers, public transit workers, those who work in the education sector (teachers, and support staff), and daycare workers.
Phase 1c: persons aged 65–74 years, persons aged 16–64 years with high-risk medical conditions, and other essential workers. Cancer has been identified as one of the high-risk medical conditions for Phase 1c.
CDC is regularly updating the number of vaccines distributed and administered at this link. ACIP continues to convene emergency meetings as new information, evidence and clinical trial results are available. Materials from previous meetings and suggested dates and agendas for future meetings can be found on their website.
Resources from the American Medical Association
The American Medical Association (AMA) has produced several resources with helpful advice for clinicians regarding the COVID-19 vaccines. Please visit the links below for concise information on the vaccines as well as tips for how to discuss them with patients.
- Physician Frequently Asked Questions
- Patient Frequently Asked Questions
- Tips on How to Talk to Patients about the Vaccine (video with transcript)
Tuesday, March 2, 2021
New Drug Shows Promise for Resistant OC
The Clearity Foundation has just released this update on the Wee1 inhibitor, currently in Phase II trials. Combined w/gemcitibine, it is showing promise in platinum-resistant OC and recurrent OC.
This article was written by Ian Ingram.
For the primary endpoint of progression-free survival (PFS) in 99 patients with high-grade serous tumors, those assigned to gemcitabine plus adavosertib had a median PFS of 4.6 months, as compared with 3.0 months with gemcitabine plus placebo (HR 0.55, 95% CI 0.35-0.90, P=0.015), reported Amit Oza, MD, of Princess Margaret Cancer Centre in Toronto, and colleagues.
Median overall survival was 11.4 months versus 7.2 months, respectively (HR 0.56, 95% CI 0.35-0.91, P=0.017).
No patients in either arm achieved a complete response, but 23% in the adavosertib arm had a partial response, as compared with 6% in the placebo arm. In an exploratory cohort of women with non-high-grade serous tumors, four patients (16%) achieved a partial response.
“Adavosertib plus gemcitabine also showed signs of activity in rare histological subtypes of ovarian cancer (serous and endometrioid, low-grade endometrioid, carcinosarcoma, and clear cell),” noted Oza and co-authors. “Interestingly, both of the two patients in the non-high-grade serous ovarian cancer cohort with available genomic profiling were KRAS mutation positive, suggesting involvement of replication stress in directing treatment response.”
In an accompanying editorial, Sarah Blagden, MD, of the University of Oxford, and Shibani Nicum, MD, of Oxford University NHS Foundation Trust in England, called the correlation of treatment response and tumor histology and molecular features “a key strength” of the study.
While sample sizes were small, adding adavosertib appeared to benefit patients with homologous recombination deficiency, BRCA mutations, and those with CCNE1-amplified tumors.
From 2014 to 2018, the double-blind phase II study randomized 99 women with high-grade serous ovarian cancer 2:1 to intravenous gemcitabine (1,000 mg/m2 on days 1, 8, and 15 of 28-day cycles) plus either oral adavosertib (175 mg on days 1, 2, 8, 9, 15, and 16) or placebo at 11 centers across the U.S. and Canada. The exploratory cohort included an additional 25 patients with non-high-grade serous disease, who all received the combination treatment.
Patients had a median age of 62 years, and a median of three prior lines of treatment. Most in the study had platinum-resistant disease, while 10% in the study arm and 15% in the control arm had primary platinum-refractory disease. To enroll, women had to have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, normal organ function, normal marrow function, and a life expectancy of 3 months or longer.
Toxicity was “generally manageable with intermittent dose modification and did not lead to severe complications,” according to the study authors.
Common grade ≥3 adverse events in the adavosertib and placebo arms, respectively, included neutropenia (62% vs 30%), leukopenia (54% vs 18%), lymphopenia (34% vs 18%), anemia (31% vs 21%), and thrombocytopenia (31% vs 6%).
Blagden and Nicum said the adavosertib dose of 175 mg “might be unnecessarily high for the heavily treated patients with high-grade serous ovarian cancer; an absence of pharmacodynamic evidence of target engagement leaves this question unanswered.”
There were no deaths related to treatment. One patient in the study arm died from sepsis, and one patient in the control arm died from disease progression.
This article was originally published by MedPage Today.