Bradley J. Monk, MD, on Ovarian Cancer: New Data on Rucaparib Monotherapy vs Placebo as Maintenance Treatment
2022 ASCO Annual Meeting
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).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
ATHENA-MONO was a randomized Phase 3 trial looking at rucaparib versus placebo in frontline maintenance after responding to platinum-based therapy. Now you may say, "We already use that." There was another study, which I'm very proud of, called PRIMA that I was the last author on. That study is very helpful and gained FDA approval as you know in April 2020, but this adds confidence to that. In fact, the ASCO guidelines say that all patients with newly diagnosed advanced ovarian cancer who respond to a platinum-based therapy should be considered for a PARP inhibitor. So hopefully if you're not doing it, you'll begin, that ATHENA-MONO will add confidence to it.
Now, the medication that we studied was rucaparib. Rucaparib is a PARP inhibitor. It has four doses, 600, 500, 400, 300. The primary endpoint was in patients who had a molecular signature consistent with homologous recombination according to the FoundationOne CDx. When we randomized patients, and they're randomized 4:1, 528 patients in 24 countries in more than 200 sites, we reached our primary endpoint.
Think of this. The hazard ratio versus placebo in the rucaparib patients, according to the HRD biomarker, which is about half of the patients based on the investigator, was 28.7 months. Think of that. Newly diagnosed advanced ovarian cancer, stage three and four that respond to platinum-based therapy now can live more than two years versus placebo where they live less than a year, 11.3 months. Based on a step-down analysis, we pivoted to an intent-to-treat analysis and it was still double: placebo, 9.2 months, the rucaparib arm, 20.2 months, hazard ratio of 0.52. Even in the biomarker negative subgroup there was still a statistically significant and clinically relevant impact in progression-free survival. Now that comes with a cost. About half of the patients required a dose reduction after an interruption, but the quality of life was maintained, and because of the dosing flexibility, again, 600, 500, 400, 300 twice daily, more than 70% of the patients could be maintained on 80% of the dose, which was 500 or 600.
What's next? Next is ATHENA-COMBO. So in this ATHENA-MONO arm, the rucaparib was the experimental arm, but in ATHENA-COMBO, which is a fully powered independent but related study, now the rucaparib is the control arm. The experimental arm now randomized 1:1, 400 patients in each arm, will be rucaparib/nivolumab. You recall that JAVELIN 100 was negative adding avelumab to frontline chemotherapy. You'll recall that IMAGINE 50 was negative adding atezolizumab to bevacizumab, but now this is maintenance in PARP plus IO.
So stay tuned. We hope to have the results to ATHENA-COMBO potentially next year against its event-driven analysis. It's my pleasure to share these data with you that were also published simultaneously in the Journal of Clinical Oncology on June 6, 2022.
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses findings from the COSMIC-021 study, which showed that cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was administered as first-line therapy in cisplatin-based chemotherapy–eligible and –ineligible patients and as second- or later-line treatment in those who received prior immune checkpoint inhibitors (Abstract 4504).
Ann H. Partridge, MD, MPH, Dana-Farber Cancer Institute, and Ian E. Krop, MD, PhD, of Yale Cancer Center, discuss phase I/II findings on patritumab deruxtecan, a HER3-directed antibody-drug conjugate, in patients with HER3-expressing metastatic breast cancer. A pooled analysis showed antitumor activity in women with HR-positive/HER2-negative and HER2-positive advanced disease, as well as triple-negative breast cancer (Abstract 1002).
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).
Michael J. Overman, MD, of The University of Texas MD Anderson Cancer Center, and Jeanne Tie, MBChB, MD, of Peter MacCallum Cancer Centre, discuss results from the DYNAMIC trial, in which a circulating tumor DNA (ctDNA)-guided approach reduced the use of adjuvant chemotherapy without compromising recurrence-free survival in patients with stage II colon cancer (Abstract LBA100).
Jenny S. Guadamuz, PhD, of Flatiron Health, discusses the use of telemedicine services in community oncology clinics for patients initiating treatments for 21 common cancers during the COVID-19 pandemic. Black, uninsured, non-urban, and less affluent patients were less likely to use telemedicine services. Although telemedicine may expand access to specialty care, the proliferation of these services may widen cancer care disparities if equitable access to these services is not ensured, according to Dr. Guadamuz (Abstract 6511).