Chemotherapy After Progression on Maintenance Olaparib in BRCA-Mutated Platinum-Sensitive Ovarian Cancer

Conference Correspondent  - ESMO 2020

The SOLO2/ENGOT Ov-21 trial was a phase 3 multicenter, international, double-blind, randomized, placebo-controlled study assessing the efficacy of olaparib maintenance therapy versus placebo in patients with platinum-sensitive, relapsed ovarian cancer with a BRCA1/2 mutation who had received at least 2 lines of previous chemotherapy. This is a post-hoc analysis of the outcomes of the first subsequent treatment in patients in the SOLO2 trial who experienced disease progression. The trial investigated the time to second progression, defined as the time between the first RECIST progression event (triggering the use of salvage chemotherapy) and the second progression event or death, in the 2 study arms.

Of the 295 patients enrolled in SOLO2, 186 patients experienced disease progression (olaparib arm, n = 106; placebo arm, n = 80) and 161 received a subsequent treatment. Of these, 147 received chemotherapy (platinum-based, n = 96; nonplatinum-based, n = 51), and 14 received other therapies.

The baseline patient characteristics of those proceeding to chemotherapy were similar, except relapsing patients in the prior olaparib maintenance arm had greater incidence of detectable disease.

The results of the post-hoc analysis showed time to second progression in patients treated with chemotherapy in the overall population was 12.6 months in the placebo arm versus 6.9 months in the olaparib arm (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.47-3.19). The time to second progression in patients treated with platinum-based chemotherapy was 14.3 months in those patients who relapsed after placebo maintenance versus 7 months in those who did so on olaparib maintenance (HR, 2.89; 95% CI, 1.73-4.82). In addition, the investigators looked at the time to second progression in patients treated with platinum-based therapy excluding the patients who had received poly (ADP-ribose) polymerase (PARP) inhibitor maintenance therapy (n = 78), and the time to second progression in this subgroup was longer in patients taking placebo prior maintenance at 14.6 months versus 7 months in patients receiving olaparib (HR, 2.33; 95% CI, 1.27-4.28). In the patients who received a nonplatinum-based chemotherapy regimen, the time to second progression was 8.3 months and 6 months in the placebo and olaparib prior maintenance arms, respectively (HR, 1.58; 95% CI, 0.86-2.90).

The findings of the post-hoc analysis of the SOLO2 trial suggest the efficacy of subsequent chemotherapy, especially platinum-based regimens, is diminished, gauged by time to second progression, in patients having received maintenance olaparib compared with placebo. The optimal management strategies for this patient population remain poorly defined and should be studied further.

Reference

Abstract and Mini-Oral Presentation 813MO. ESMO 2020. September 19-21, 2020. Efficacy of subsequent chemotherapy for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib vs placebo: the SOLO2/ENGOT Ov-21 trial.

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Last modified: September 22, 2020