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Over the past year, several important studies in ovarian cancer have been presented at multiple oncology meetings and published in a number of peer-reviewed publications. In this installment of a two-part discussion for The ASCO Post Newsreels, Ursula A. Matulonis, MD, and Joyce F. Liu, MD, MPH, discuss antibody-drug conjugates and clinical trials including PRIMA and ATHENA. In part two of this feature, Dr. Matulonis and Dr. Liu talk about low-grade serous ovarian carcinoma and an important recently published study. Filmed November 22, 2024
This is Part 3 of Overcoming Platinum Resistance in Ovarian Cancer: New Strategies and Novel Targets, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Kathleen Moore, Katherine Fuh, and Bhavana Pothuri discuss the treatment of advanced ovarian cancer after progression on both platinum-based therapy and a PARP inhibitor. The patient is a 72-year-old woman with a history of stage IIIC high-grade serous ovarian cancer diagnosed in 2019. Molecular profiling revealed that she is BRCA wild-type and HRD-positive. She was treated with neoadjuvant paclitaxel and carboplatin plus bevacizumab, followed by bevacizumab maintenance for 1 year. Twenty-four months after her last platinum-based therapy, she experienced disease recurrence with liver metastases. At the time of her recurrence, she was treated with carboplatin and pegylated liposomal doxorubicin for six cycles and had a partial response. She was then treated with maintenance olaparib for 12 months, experienced disease progression, and returned to carboplatin monotherapy. Unfortunately, after four cycles of carboplatin, her disease progressed again. In the conversation that follows, the faculty discuss whether prior progression on a PARP inhibitor and platinum-based therapy influence their choice of therapy in the platinum-resistant setting, the role of HER2-targeting antibody-drug conjugates, and the importance of next-generation sequencing and testing for immunohistochemistry to better match patients to clinical trials.
This is Part 2 of Overcoming Platinum Resistance in Ovarian Cancer: New Strategies and Novel Targets, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Kathleen Moore, Katherine Fuh, and Bhavana Pothuri discuss the treatment of advanced ovarian cancer when progression of disease has occurred after platinum-based therapy. The patient is a 66-year-old woman with a history of stage IIIC high-grade serous ovarian cancer diagnosed in 2019. She was treated with primary cytoreductive surgery with no gross residual disease, followed by paclitaxel and carboplatin plus bevacizumab, and then bevacizumab maintenance for 1 year. She is BRCA wild-type and HRD-negative. Eighteen months after her last platinum, she experienced disease recurrence with abdominal disease and subsequently received carboplatin and pegylated liposomal doxorubicin plus bevacizumab for six cycles, achieving a partial response. Unfortunately, 5 months after her last platinum, she experienced disease recurrence again, with liver metastases and moderate ascites. In the conversation that follows, the faculty discuss key biomarkers to look for when determining a patient’s treatment course, whether platinum-based therapy is ever warranted in the setting of platinum resistance, the role of folate receptor inhibitors, and new therapies on the horizon.
This is Part 1 of Overcoming Platinum Resistance in Ovarian Cancer: New Strategies and Novel Targets, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Kathleen Moore, Katherine Fuh, and Bhavana Pothuri discuss the treatment of advanced ovarian cancer with disease progression on platinum-based therapy. The patient is a 75-year-old woman with a history of stage IV high-grade endometrioid ovarian cancer diagnosed in 2020. She is BRCA wild-type. She was treated with neoadjuvant paclitaxel and carboplatin for three cycles and underwent successful interval cytoreductive surgery. She then received three additional cycles of paclitaxel and carboplatin and 1 year of niraparib maintenance, at which point she was found to have progressive disease. Following recurrence, she received carboplatin and pegylated liposomal doxorubicin plus bevacizumab for three cycles until her disease progressed again. She is now considered to be platinum-resistant. In the conversation that follows, the faculty discuss patient-specific considerations when choosing therapy for platinum-resistant ovarian cancer, the importance of obtaining tissue for thorough biomarker evaluation to assess eligibility for clinical trials, and current standard of care options.
Yukio Suzuki, MD, PhD, of Columbia University College of Physicians and Surgeons, discusses data showing that reproductive-age patients with early-stage endometrial cancer who use fertility-preserving hormonal therapy seemed to have good overall survival after a 10-year follow-up (Abstract 5508).
Alex Andrea Francoeur, MD, of UC Irvine Health, discusses data showing an association between the increasing incidence of endometrial cancer and obesity, which disproportionately affects younger women and women of color. According to Dr. Francoeur, the findings warrant targeted health services and public health interventions to stabilize and ultimately reverse the rising rates (Abstract 5507).
Mostafa Eyada, MD, of The University of Texas MD Anderson Cancer Center, discusses study results showing that bevacizumab in combination with oral cyclophosphamide had a response rate of 40% in patients with recurrent platinum-resistant high-grade ovarian cancer (Abstract 5517).
Jean-Marc Classe, MD, PhD, of France’s Nantes Université, discusses phase III results showing that systematic lymphadenectomy should be omitted in patients with advanced epithelial ovarian cancer with clinically negative lymph nodes, as well as those undergoing neoadjuvant chemotherapy and interval complete surgery (LBA5505).
Don S. Dizon, MD, of Legorreta Cancer Center at Brown University and Lifespan Cancer Institute, discusses final phase II results of the BrUOG 354 trial showing that, for patients with ovarian and other extrarenal clear cell cancers, nivolumab and ipilimumab warrant further evaluation against standard treatment, given the historically chemotherapy-resistant nature of the disease (LBA5500).
Katherine C. Fuh, MD, PhD, of the University of California, San Francisco, discusses phase III findings of the AXLerate-OC trial, showing that batiraxcept with paclitaxel compared to paclitaxel alone improved progression-free and overall survival in patients with platinum-resistant recurrent ovarian cancer whose tumors were AXL-high in an exploratory analysis (LBA5515).
Ana Oaknin, MD, PhD, of Spain’s Vall d’Hebron University Hospital, discusses phase III findings from the BEATcc trial, showing that adding atezolizumab to a standard bevacizumab-plus-platinum regimen for patients with metastatic, persistent, or recurrent cervical cancer significantly improves survival outcomes and may be considered a new first-line treatment option.
Matthew A. Powell, MD, of the Washington University School of Medicine, discusses phase III findings from the RUBY trial, which shows dostarlimab-gxly plus chemotherapy improves overall survival in patients with primary advanced or recurrent endometrial cancer, regardless of mismatch repair status. According to Dr. Powell, this regimen could become a new standard of care.
Anne Knisely, MD, of The University of Texas MD Anderson Cancer Center, discusses study findings showing that patients with ovarian cancer who undergo second-look laparoscopy and are found to have measurable residual disease (MRD) as well as circulating tumor DNA (ctDNA) after front-line therapy have a particularly poor prognosis. These data suggest treatments should be individualized by stratifying risk, and front-line clinical trials of ovarian cancer should use MRD as a surrogate endpoint.
Mary McCormack, PhD, MBBS, of University College London Hospitals, NHS Foundation Trust, discusses the global health issue of cervical cancer and a way forward. Phase III findings from the GCIG INTERLACE trial showed that induction chemotherapy with weekly paclitaxel and carboplatin before chemoradiation not only improved survival outcomes, it is feasible across diverse health-care settings and may be considered a new standard in locally advanced cervical cancer.
Mansoor R. Mirza, MD, of Copenhagen University Hospital, discusses follow-up results from the RUBY trial, showing that, for patients with primary advanced or recurrent endometrial cancer, dostarlimab-gxly plus chemotherapy followed by dostarlimab-gxly plus niraparib improved progression-free survival in the overall and subgroup populations. Given the potential role for PARP inhibitor maintenance, the study is ongoing to obtain overall survival data.
Brian M. Slomovitz, MD, of Mount Sinai Medical Center, Miami Beach, discusses additional phase III data from the innovaTV 301 trial, which showed that in patients with previously treated recurrent or metastatic cervical cancer, tisotumab vedotin-tftv was more efficacious than chemotherapy as second- or third-line treatment. According to Dr. Slomovitz, this agent may be considered a potential new standard of care in this population.
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Mansoor R. Mirza, MD, of Denmark’s Rigshospitalet and Copenhagen University Hospital, discuss new findings on dostarlimab-gxly plus carboplatin/paclitaxel, which improved progression-free survival while maintaining health-related quality of life, further supporting its use as a standard of care in primary advanced or recurrent endometrial cancer (Abstract 5504).
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Isabelle L. Ray-Coquard, MD, PhD, of Centre Léon Bérard and the University Claude Bernard Lyon Est, discuss findings from the COLIBRI trial, which showed that, for patients with cervical squamous cell carcinoma, neoadjuvant nivolumab plus ipilimumab is safe and orchestrates de novo immune responses. The 82.5% complete response rate for primary tumors 6 months after standard chemoradiation therapy suggests favorable clinical outcomes (Abstract 5501).
Bobbie J. Rimel, MD, of Cedars-Sinai Medical Center, and Kathleen N. Moore, MD, of the Stephenson Oklahoma Cancer Center at the University of Oklahoma, discuss phase III results from the MIRASOL trial, which showed that mirvetuximab soravtansine-gynx prolonged overall survival vs investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer with high folate receptor-alpha expression. The findings suggest a new standard of care for this disease (Abstract LBA5507).
Bradley J. Monk, MD, of the University of Arizona, Phoenix, and Creighton University, discusses phase III findings from the KEYNOTE-826 study of overall survival results in patients with persistent, recurrent, or metastatic cervical cancer. Study participants received first-line treatment of pembrolizumab plus chemotherapy, with or without bevacizumab, which reduced the risk of death by up to 40% in three different subsets of patients (Abstract 5500).
Marie Plante, MD, of Canada’s Université Laval and the CHUQ Hotel Dieu de Québec, discusses phase III results from a study that compared radical hysterectomy and pelvic node dissection vs simple hysterectomy and pelvic node dissection in patients with low-risk early-stage cervical cancer. The pelvic recurrence rate at 3 years in the women who underwent simple hysterectomy is not inferior to those who had radical hysterectomy. In addition, fewer surgical complications and better quality of life were observed with simple hysterectomy (LBA5511).
Mansoor R. Mirza, MD, of Copenhagen’s Rigshospitalet, discusses phase III data from the ENGOT-EN6-NSGO/GOG-3031/RUBY study, which showed that, compared with carboplatin and paclitaxel alone, dostarlimab-gxly plus carboplatin and paclitaxel increased progression-free survival in patients with primary advanced or recurrent endometrial cancer that is mismatch repair–deficient/microsatellite instability–high. An early trend toward improved overall survival was observed in all populations. This regimen may represent a new standard of care for patients, says Dr. Mirza.
Ursula A. Matulonis, MD, of Dana-Farber Cancer Center discusses the ENGOT-OV16/NOVA study, which initially showed that niraparib maintenance therapy significantly prolonged progression-free survival in patients with platinum-sensitive recurrent ovarian cancer, regardless of germline BRCA mutation or homologous recombination deficiency biomarker status. Here, Dr. Matulonis details the final phase III findings on overall survival and the long-term safety of niraparib in this population.
Shannon N. Westin, MD, MPH, of The University of Texas MD Anderson Cancer Center, discusses results from the NOW study, which showed that neoadjuvant olaparib is feasible and has a good safety profile in patients with mutated, advanced-stage ovarian cancer. Even in patients with stage IV disease, surgical outcomes were favorable after two cycles of olaparib, justifying further study to determine whether PARP inhibitors can be given in lieu of chemotherapy in the neoadjuvant setting.
Shannon N. Westin, MD, MPH, of The University of Texas MD Anderson Cancer Center, discusses new findings on the combination of olaparib and selumetinib, which benefited patients with RAS-mutant ovarian and endometrial cancers. This combination will be explored further in these select cohorts in the upcoming ComboMATCH trial to clarify the relative contribution of each drug.
Ana Oaknin, MD, PhD, of Barcelona’s Vall d’Hebron University Hospital, discusses findings from the CheckMate 358 trial, which showed that chemotherapy-free immunotherapy with nivolumab alone or in combination with ipilimumab may provide durable tumor regression with manageable toxicity in patients with recurrent or metastatic cervical cancer, regardless of tumor PD-L1 expression (Abstract 520MO).
Ana Oaknin, MD, PhD, of Barcelona’s Vall d’Hebron University Hospital, discusses an analysis of long-term survival from the EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial. Cemiplimab-rwlc is the first immunotherapy to demonstrate an overall survival benefit as a second-line monotherapy for patients with recurrent or metastatic cervical cancer previously treated with platinum-based chemotherapy but not immunotherapy. The benefit was sustained in this population (Abstract 519MO).
Paul A. DiSilvestro, MD, of Women & Infants Hospital and the Warren Alpert Medical School of Brown University, discusses overall survival results after a 7-year follow-up of the SOLO1/GOG-3004 trial for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation who received maintenance olaparib. Dr. DiSilvestro details the increasing role of such PARP inhibitors in ovarian cancer treatment and their benefit to patients (Abstract 517O).
Bradley J. Monk, MD, of the University of Arizona College of Medicine and Creighton University School of Medicine, discusses phase III findings from the ATHENA–MONO (GOG-3020/ENGOT-ov45) trial. It showed that rucaparib as first-line maintenance treatment, following first-line platinum-based chemotherapy, improved progression-free survival in patients with ovarian cancer, irrespective of homologous recombination deficiency status (Abstract LBA5500).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Domenica Lorusso, MD, PhD, of Italy’s Gemelli University Hospital, discuss phase III data from the MITO23 trial on single-agent trabectedin vs clinician’s choice of chemotherapy in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancers of BRCA-mutated or BRCAness phenotype. Although trabectedin has demonstrated antitumor activity in relapsed platinum-sensitive disease, it does not appear to improve survival outcomes when compared with standard chemotherapy in the BRCA-mutated population (Abstract LBA5504).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Ignace Vergote, MD, PhD, of Belgium’s University Hospitals Leuven, discuss interim safety and efficacy results from a third dose-expansion cohort evaluating first-line tisotumab vedotin-tftv plus pembrolizumab in patients with recurrent or metastatic cervical cancer. Data on the combination showed durable antitumor activity with a manageable safety profile (Abstract 5507).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Nicoletta Colombo, MD, of the University of Milan and the European Institute of Oncology, discuss phase II results on the overall survival benefit of intermittent relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel, compared with nab-paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer. A phase III trial comparing intermittent relacorilant plus nab-paclitaxel with investigator’s choice of chemotherapy in primary platinum-refractory disease is ongoing (Abstract LBA5503).
Benoit You, MD, PhD, of Lyon University hospital (HCL, France) and GINECO group (France), discusses findings from the GOG-0218 trial of patients with ovarian cancer, which appears to confirm earlier data on the link between poor tumor chemosensitivity and benefit from concurrent plus maintenance bevacizumab. In Dr. You’s validation study, patients who derived the most progression-free and overall survival benefit from bevacizumab were those with high-risk disease (stage IV or incompletely resected stage III) associated with an unfavorable KELIM score (CA-125 kinetic elimination rate constant, calculable online) (Abstract 5553).
Pedro T. Ramirez, MD, of The University of Texas MD Anderson Cancer Center, discusses the final analysis of the LACC trial (Laparoscopic Approach to Cervical Cancer), which showed that women with early cervical cancer who need a radical hysterectomy may have worse outcomes with minimally invasive surgery compared with open surgery. All treatment guidelines support open surgery, which yields similar outcomes in terms of complications and quality of life (Abstract LBA10).
Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, discusses findings from the SORAYA study on the efficacy and safety of mirvetuximab soravtansine in patients who have platinum-resistant ovarian cancer with high folate receptor–alpha expression. Based on the results, Dr. Matulonis believes this agent might become a practice-changing, biomarker-driven standard-of-care treatment option (Abstract LBA4).
Timothy A. Yap, MBBS, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the PETRA study, a first-in-class, first-in-human trial of the next-generation PARP1-selective inhibitor AZD5305 in patients with BRCA1/2, PALB2, or RAD51C/D mutations in advanced or metastatic ovarian cancer, HER2-negative breast cancer, pancreatic, or prostate cancer. Target engagement was demonstrated across all dose levels, and antitumor activity was observed in selected tumor and molecular subtypes.
Benoit You, MD, PhD, of the Lyon University Hospital (France), discusses phase I/II safety and efficacy results from the ENDOLA trial that combined olaparib with metronomic cyclophosphamide and metformin in patients with advanced pretreated endometrial cancer. At 10 weeks, the non–disease progression rate was 61.5%, reaching the primary endpoint of the study. Median progression-free survival was 5.1 months. Research on biomarkers of efficacy is ongoing (Abstract CT005).
Susana N. Banerjee, MBBS, PhD, of The Royal Marsden NHS Foundation Trust, discusses phase I results that have generated interest in the combination of the RAF/MEK inhibitor VS-6766 and the FAK inhibitor defactinib for patients with recurrent low-grade serous ovarian cancer, a disease that typically has limited response to conventional chemotherapy and hormonal therapy. The data support ongoing investigation (Abstract 725MO).
Susana N. Banerjee, MBBS, PhD, of The Royal Marsden NHS Foundation Trust, discusses phase II results of the EORTC-1508 trial, the first study to combine an anti–PD-L1 antibody, atezolizumab, with bevacizumab and the COX1/2 inhibitor acetylsalicylic acid as treatment for patients with ovarian, fallopian tube, or primary peritoneal adenocarcinoma (Abstract LBA32).
Nicoletta Colombo, MD, of the Istituto Europeo Oncologico, discusses phase III results that showed improvements in progression-free and overall survival with a combination of pembrolizumab plus chemotherapy, compared with placebo and chemotherapy, for patients with persistent, recurrent, or metastatic cervical cancer. These benefits were seen regardless of PD-L1 expression and concomitant bevacizumab use, suggesting that pembrolizumab plus chemotherapy, with or without bevacizumab, may be a new standard of care for this population (Abstract LBA2).
Linda R. Mileshkin, MBBS, MD, of the Peter MacCallum Cancer Centre, discusses phase III findings from the OUTBACK trial, which showed that adjuvant chemotherapy given after standard cisplatin-based chemoradiation for women with locally advanced cervical cancer did not improve either overall or progression-free survival (Abstract LBA3).
In this video, Ursula Matulonis, MD; Joyce F. Liu, MD, MPH; and Bobbie J. Rimel, MD, focus on a case of mismatch repair–deficient/microsatellite instability–high recurrent endometrial cancer. They discuss the range of treatment options for patients with mismatch repair–deficient cancer, including the potential utility of single-agent immune checkpoint inhibitors such as pembrolizumab.
Ursula Matulonis, MD; Joyce F. Liu, MD, MPH; and Bobbie J. Rimel, MD, discuss the appropriate management of an older patient with mismatch repair–proficient recurrent endometrioid endometrial cancer, highlighting the importance of histology when determining the best treatment option for patients such as these. They review data from the phase III KEYNOTE-775 study, presented recently at the SGO 2021 Annual Meeting on Women’s Cancer, which evaluated pembrolizumab and lenvatinib in advanced endometrial cancer, and discuss the clinical implications of the findings.
Ursula Matulonis, MD; Joyce F. Liu, MD, MPH; and Bobbie J. Rimel, MD, discuss a case of a woman with platinum-sensitive recurrent ovarian cancer who was found to have a germline BRCA1 mutation. They address the question of how to choose the optimal chemotherapy regimen for patients who are platinum-sensitive, whether maintenance bevacizumab or poly (ADP-ribose) polymerase inhibitors are appropriate, and how to manage adverse events. Recent data from SOLO-2 and ENGOT-OV16/NOVA are discussed.
In this video, Ursula Matulonis, MD; Joyce F. Liu, MD, MPH; and Bobbie J. Rimel, MD, discuss the use of poly (ADP-ribose) polymerase (PARP) inhibitors in the management of a patient with newly diagnosed, advanced ovarian cancer with a germline BRCA1 mutation. They review recent findings from the SOLO-1, PRIMA, and PAOLA-1 trials and provide insights into the management of adverse events that may arise from maintenance therapy with PARP inhibitors such as niraparib and olaparib.
Anthony B. Costales, MD, of the Baylor College of Medicine, discusses results from the MIID-SOC trial, which explored the question of whether laparoscopic surgery for removal of ovarian, fallopian tube, or primary peritoneal cancer following neoadjuvant chemotherapy is feasible, safe, and provides similar outcomes as open surgery.
Andreas Obermair, MD, of the University of Queensland and Queensland Centre for Gynaecological Cancer Research, discusses data on a hormonal IUD used to treat women with the precursor lesion endometrial hyperplasia with atypia (EHA) and those with stage I endometrial adenocarcinoma (EAC). At 6 months, the data showed a complete pathologic response in 82% of patients with EHA and in 43% of those with EAC (ID# 10244).
Amir A. Jazaeri, MD, of The University of Texas MD Anderson Cancer Center, discusses data on the safety and efficacy of adoptive cell transfer using autologous tumor-infiltrating lymphocytes (LN-145) to treat patients with recurrent, metastatic, or persistent cervical carcinoma whose tumors have progressed on prior systemic therapy (ID # 10224).
Eric Pujade-Lauraine, MD, PhD, of Hôpital Hôtel-Dieu, discusses results from the PAOLA-1ENGOT-ov25 trial on the use of homologous recombination–repair mutation gene panels and whether they can predict the efficacy of olaparib plus bevacizumab in first-line maintenance therapy for patients with ovarian cancer (ID# 10224).
Brittany A. Davidson, MD, of Duke University, discusses the development and validation of the GO-POP model (Gynecologic Oncology Predictor of Postoperative opioid use), an individualized patient-centered predictive tool designed to help avoid overprescribing pain medications (ID# 10253).