Thomas J. Herzog, MD, Deputy Director, University of Cincinnati Cancer Center, who presented a distillation of the PAOLA-1 trial findings along with updated results of the PRIMA trial, called the difference in progression-free survival with the addition of olaparib to bevacizumab “remarkable” after upfront surgery with no residual disease.1
Thomas J. Herzog, MD
“Compared with bevacizumab alone, progression-free survival improved by more than 17 months with the combination therapy in patients who received upfront surgery that achieved complete debulking,” said Dr. Herzog. “You would expect these patients to do well and better than the others because of selection bias for favorable biology, but the fact that you saw such a significant difference is very interesting, especially when you consider the historical front-line use of bevacizumab in subgroups from GOG218, for example, where residual disease was required.”
Challenges in Clinically Applying These Results
Although these data may be practice-changing, said Dr. Herzog, clinicians are still left with challenges in applying these results. There are barriers to cross-trial comparisons, for example, between PAOLA-1 and the pivotal PRIMA trial that led to the recent approval by the U.S. Food and Drug Administration of niraparib for first-line maintenance of advanced ovarian cancer.
“Patients in PRIMA were randomly assigned to niraparib vs matched placebo, but it’s very important to point out there was an active control in PAOLA-1,” explained Dr. Herzog. “At the same time, PAOLA-1 suffered from the fact that patients who underwent primary debulking surgery had received optimal cytoreduction to get in, so you couldn’t really tell if there was a response based on a measurable lesion.”
Ultimately, said Dr. Herzog, as clinicians await data from the phase II OVARIO trial, interpretation of results from PAOLA-1 may depend on whether or not one uses bevacizumab already. According to Dr. Herzog, approximately 40% to 50% of providers in the United States and 60% or more in Europe use bevacizumab in the first-line setting.
Additional Commentary
Kathleen N. Moore, MD
Kathleen N. Moore, MD, Associate Professor of Gynecologic Oncology and Director of the Oklahoma TSET Phase I Clinical Trials Program, Stephenson Cancer Center, Oklahoma City, acknowledged the difficulty of deciding whether olaparib plus bevacizumab is the standard of care for patients with BRCA-associated cancers based on PAOLA-1 data because of the absence of an olaparib-alone arm. Nevertheless, said Dr. Moore, propensity-weighted analysis of the phase III SOLO1 trial,2 which randomly assigned women with BRCA1/2-mutated advanced ovarian cancer to olaparib or placebo maintenance after first-line treatment, suggests a benefit to adding olaparib.
“There’s likely some additional benefit,” said Dr. Moore. “Of note, for providers who use bevacizumab and were concerned about stopping, PAOLA-1 provides evidence that it’s okay to continue and add olaparib on top.”
DISCLOSURE: Dr. Herzog is on the scientific advisory boards for AbbVie, AstraZeneca, Caris, Clovis, Genentech, GSK, Johnson & Johnson, Merck, and Myriad. Dr. Moore has served on advisory boards for AbbVie, Aravive, AstraZeneca, Clovis, Eisai, Genentech/Roche, GSK/Tesaro, Immunogen, Merck, Mersana, Tarveda, VBL Therapeutics, and Vavotar; has participated in educational programming with Research to Practice, Cue, Prime, and Curio; and received institutional research funding from PTC Therapeutics, Merck, GSK/Tesaro, and Lilly.
REFERENCES
1. Herzog TJ: Paradigm changes in front-line ovarian cancer: 2020 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Webinar 2. Presented April 29, 2020.
2. Moore K, Colombo N, Scambia G, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379:2495-2505, 2018.
