Quality of Life Sustained With Maintenance Olaparib Rechallenge in Platinum-Sensitive Ovarian Cancer

Patient-reported outcome data from the phase 3b OReO/ENGOT-ov38 trial showed no significant effect on quality of life following rechallenge with maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer.

Rechallenge with maintenance olaparib (Lynparza) did not significantly impact health-related quality of life (HRQoL) for patients with platinum-sensitive relapsed ovarian cancer (PSROC), according to recent data from the phase 3b OReO/ENGOT-ov38 trial (NCT03106987) presented in a poster at the 2022 Annual Global Meeting of the International Gynecologic Cancer Society.

Investigators found no clinically significant differences in Functional Assessment of Cancer Therapy – Ovarian (FACT-O) trial outcome index (TOI) scores with olaparib maintenance vs placebo, and all 95% confidence intervals were within the minimally important difference (MID) interval of 10 points. Patients with BRCA mutations had a between group difference in TOI score of –2.94 points (95% CI, –4.99 to –0.90, P = .005) and those without mutations had a difference of –2.66 points (95% CI, –4.75 to –0.58, P = .013), which was not considered clinically meaningful in either case. Moreover, most patients treated with olaparib and placebo had a best response of no change in TOI scores, and few experienced deteriorations defined as a 10-point or greater decrease from baseline. In the BRCA-mutated cohort, scores deteriorated for 14% of patients treated with olaparib vs 11% with placebo; in the non–BRCA-mutated cohort, scores deteriorated for 15% and 6%, respectively.

In addition to these primary quality-of-life data, similar proportions of patients across all 4 subgroups reported improvements in TOI scores.

In patients with BRCA1/2 mutations, previous findings established a median progression-free survival (PFS) of 4.3 months achieved with olaparib (n = 74) vs 2.8 months with placebo (n = 38) for the indicated patient population (HR 0.57; 95% CI, 0.37–0.87, P = .022). This difference in outcomes also occurred in patients without BRCA1/2 mutations, for whom median PFS was 5.3 months with olaparib (n = 72) vs 2.8 months with placebo (n = 36; HR 0.43; 95% CI, 0.26–0.71, P = .002). Taken together, these findings suggest maintenance olaparib rechallenge may be effective and tolerable in this patient population.

“Olaparib maintenance retreatment was found to be effective in delaying disease worsening without affecting patients’ sense of wellbeing and their ability to carry out their normal daily activities,” investigators concluded.

This randomized, double-blind, placebo-controlled study was the first to examine olaparib maintenance rechallenge in patients with PSROC who respond to platinum-based chemotherapy and have received at least 1 prior PARP inhibitor. In total, 220 participants were split into cohorts according to BRCA mutation status and randomized 2:1 to receive either oral olaparib tablets at 300 mg twice daily or a matching placebo. To be eligible for inclusion, patients must have had at least 1 prior PARP inhibitor therapy, a life expectancy no less than 16 weeks, and an ECOG performance status no greater than 1.

FACT-O TOI scores ranged from 0 to 100. Higher scores indicated better quality of life, and a difference of 10 points indicated a clinically significant change. Patients completed questionnaires prior to dosing at baseline, at day 29, every 4 weeks for the first 12 weeks thereafter, and then every 12 weeks until 2 years from randomization.

The duration of prior PARP inhibitor therapy was largely constant across all 4 patient subgroups. Those with BRCA-mutated disease who received olaparib had prior therapy for a median of 21.2 months (range, 12-58) vs 18.3 months (range, 12-55) in those who received placebo. In those without BRCA-mutated disease, corresponding median duration of therapy was 12.6 months (range, 6-102) and 12.4 months (range, 3-36).

References

  1. Redondo A, Follana P, Scambia G, et al. Maintenance olaparib rechallenge in patients with ovarian cancer previously treated with a PARP inhibitor: patient-reported outcomes from the phase IIIB OREO/ENGOT-OV38 trial. Presented at: 2022 Annual Global Meeting of the International Gynecologic Cancer Society; New York, NY; September 29-October 1, 2022. Abstract O025.
  2. Pujade-Lauraine E, Selle F, Scambia G, et al. Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): Phase IIIb OReO/ENGOT Ov-38 trial. Ann Oncol. 2021;32(suppl 5):LBA33. doi:10.1016/annonc/annonc741