Subsequent Chemotherapy Following Olaparib Maintenance Therapy in BRCA1/2 Mutated Platinum-Sensitive Recurrent Epithelial Ovarian Cancer

2020 Year in Review - Ovarian Cancer

Is subsequent chemotherapy less effective for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer who have been treated with olaparib as maintenance therapy? Here we discuss the latest findings from the SOLO2/ENGOT Ov-21 clinical trial.

Jean-Sébastien Frenel, MD, Medical Oncologist and Researcher, Gynecological Cancer, Institut de Cancérologie de l’Ouest, Centre René Gauducheau, Saint-Herblain, France, presented the latest results from the SOLO2/ENGOT Ov-21 clinical trial that investigated whether subsequent chemotherapy is less effective in the study population after olaparib treatment.

Previous analysis from the SOLO2/ENGOT Ov-21 trial demonstrated that maintenance therapy with olaparib in patients with platinum-sensitive recurrent epithelial ovarian cancer and a BRCA1/2 mutation led to clinically significant survival benefit. Pujade-Lauraine and colleagues showed that olaparib provided a significant progression-free survival improvement with no detrimental effect on quality of life in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation.1 Furthermore, aside from anemia, toxicities were found to be generally manageable and low grade. The latest findings reported at the European Society for Medical Oncology Virtual Congress 2020 focused on the efficacy of subsequent chemotherapy at the time of disease progression.

This latest analysis focused on first subsequent treatment in patients who progressed according to standard Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, which were developed and tested using data from clinical trials testing cytotoxic drugs. From the date of RECIST progression after olaparib maintenance to next progression or death as a surrogate of first post-olaparib treatment progression-free survival, a post-hoc analysis of time to second progression was calculated.

Between both arms, patient baseline demographics were roughly balanced. The researchers found that in the olaparib and placebo arms, 54% (106/195) and 81% (80/99) of patients had a RECIST progression. Receiving a first subsequent therapy were 87% (161/186) of patients, including chemotherapy in 93% (150/161) and a poly (ADP-ribose) polymerase (PARP) inhibitor in 18% (29/161) and all patients in the placebo arm. The study findings showed that 44% and 56% of patients in the placebo arm received a nonplatinum and a platinum-based chemotherapy, respectively, compared with 37% and 63% of patients in the olaparib arm. Furthermore, in patients receiving subsequent treatment, time to second progression was longer in the placebo arm compared with the olaparib arm: 11.1 months versus 7 months (hazard ratio, 1.93; 95% confidence interval, 1.35-2.76). Time to second progression was 14.3 versus 7 months with platinum-based chemotherapy and 8.3 versus 5.5 months with nonplatinum chemotherapy in the placebo and olaparib arms, respectively.

The authors concluded that in this post-hoc evaluation, some degree of resistance to standard subsequent platinum and nonplatinum chemotherapy is demonstrated in the olaparib arm; this was measured by time to second progression. It should be noted, however, that the reduction in time to second progression is not at the expense of overall survival, perhaps implying that the use of olaparib in an earlier manner affords benefits in this population. To elucidate optimal post olaparib management strategies, a prospective study should be conducted.

Source: Frenel J-S, et al. Ann Oncol. 2020;31(4_suppl). Abstract 813MO.

Reference
1. Pujade-Lauraine E, Ledermann JA, Selle F, et al; for the SOLO2/ENGOT-Ov21 Investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1274-1284. Erratum in: Lancet Oncol. 2017;18:e510.

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