Maintenance treatment with olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, enhanced survival in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation, according to a study published in The Lancet Oncology.
Previous data from the SOLO2/ENGOT-Ov21 phase 3 trial (ClinicalTrials.gov Identifier: NCT01874353) had shown prolonged progression-free survival in patients treated with olaparib who had relapsed high-grade serous or endometrioid ovarian cancer, were sensitive to platinum therapy, and had a BRCA1 or BRCA2 (BRCA1/2) mutation. Investigators performed a final analysis of SOLO2 to investigate the effect of olaparib on overall survival (OS), in a double-blind, randomized phase 3 trial across 123 medical centers in 16 countries.
The study enrolled 295 patients who were randomly assigned to receive oral olaparib 300 mg in two 150-mg tablets, twice daily (196 patients) or matching placebo (99 patients). One patient, randomized in error, did not receive olaparib or matching placebo. The baseline characteristics were well-balanced between the 2 groups, with confirmed Myriad germline BRCA1/2 mutation present in 97% of the olaparib group and 97% of the placebo group. A confirmed germline BRCA1/2 mutation was present in the each of the 2 groups (3%). After disease progression, 10% of the patients in the olaparib group and 38% of the patients in the placebo group received subsequent poly-ADP ribose polymerase (PARP) inhibitor therapy either as monotherapy or as maintenance therapy followed by platinum-based chemotherapy.
The median follow-up for OS was 65.7 months (interquartile range, 63.6-69.3) for olaparib and 64.5 months (63.4-68.7) for placebo. The median OS was 51.7 months (95% CI, 41.5-59.1) for the olaparib group and 38.8 months (31.4-48.6) for the placebo group (hazard ratio, 0.74; 95% CI, 0.54-1.00; P =.054), not adjusted for 38% of the patients in the placebo group who received subsequent PARP inhibitor therapy.
The most frequently reported grade 3 or worse treatment-emergent adverse event (TEAE) was anemia, which occurred in 21% of the patients in the olaparib group and 2% in the placebo group. Serious TEAEs were reported in 26% of the patients receiving olaparib and 8% of the patients receiving placebo. Three patients who received olaparib had TEAEs resulting in a fatal outcome that was attributed to myelodysplastic syndrome, and 3 patients who received olaparib had acute myeloid leukemia.
The median OS was 12.9 months for the olaparib group compared with placebo in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation. The study authors concluded that “Although the improvement in overall survival with olaparib was not statistically significant, it is arguably clinically meaningful, and thus the findings support the use of maintenance olaparib in this patient group.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ affiliations.
Poveda A, Floquet A, Lederman JA, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(5):620-631. doi:10.1016/ S1470-2045(21)00073-5