Charlie Gourley, PhD, MBChB
In final results from the phase II Study 19 trial, the PARP inhibitor olaparib (Lynparza) demonstrated clinically significant, long-term treatment benefits in patients with platinum-sensitive relapsed serous ovarian cancer.1
Median overall survival (OS) was 29.8 months for patients treated with olaparib versus 27.8 months with placebo (HR, 0.73; 95% CI, 0.55-0.95), according to findings presented at the 2017 ASCO Annual Meeting. Of 129 patients on placebo, 112 (86.8%) experienced an OS event.
As of the May 9, 2016, data cutoff, the median OS was 78 months at a data maturity of 79%. Fifteen patients (11%) were still receiving olaparib after being on treatment for 6 or more years, including 8 patients with BRCA mutations. One BRCA-mutated patient was still receiving placebo.
Investigators also found that maintenance therapy with olaparib significantly improved progression-free survival compared with placebo in patients with platinum-sensitive relapsed serous ovarian cancer (HR, 0.35; 95% CI, 0.25-0.49).1
In an interview with OncLive
, lead author Charlie Gourley, MB ChB, PhD, chair of medical oncology and honorary consultant in medical oncology at the University of Edinburgh Cancer Research UK Centre, emphasized the durability of the response, especially among the BRCA
-mutated and BRCA
“This 6+ year response is unprecedented in the relapsed ovarian cancer setting,” he said. “What’s more, once a patient made it to 4 years without relapse, we saw very little drop-off.”
However, he offered a caveat regarding the current data.
“This final OS analysis was protocol-specified but not designed to show a statistically significant difference between treatment arms,” he said. “The current OS analysis should therefore be considered descriptive, with P values deemed nominal.” OS was analyzed using a Cox proportional hazards model.
The randomized, double-blind Study 19 evaluated outcomes with olaparib in 265 patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. They had received 2 or more prior regimens of platinum-based chemotherapy and experienced complete response or partial response to their most recent regimen. Roughly half of patients (n = 136) received olaparib 400 mg capsules twice daily as maintenance therapy, while 129 received placebo capsules twice daily until disease progression.
Patients with a BRCA
mutation derived the greatest benefit from olaparib. The BRCA
-mutated patient data were at 73% maturity at cutoff. Among the olaparib patients (n = 74), 7 were on treatment at data cutoff and 8 had been on treatment for 6 or more years.
Forty-nine patients (66.2%) had experienced OS events, and the median OS was 34.9 months (HR, 0.62; 95% CI, 0.42-0.93). The placebo group (n = 62) contained 1 patient who was on treatment at data cutoff and had been on treatment for 6 or more years. Fifty patients (80.6%) experienced an OS event and median OS was 30.2 months.
For patients with BRCA wild-type, data had reached 86% maturity at cutoff. The olaparib group (n = 57) included 7 patients on treatment at cutoff and who had been on treatment more than 6 years.
Median OS was 24.5 months (HR, 0.84; 95% CI, 0.57-1.25) and 78.9% of patients experienced an OS event. There were no patients assigned to placebo in this group who were still on treatment; 57 (93.4%) had experienced an OS event. Their median OS was 26.6 months.
Fifteen patients received olaparib for 6+ years. Nine of those patients had a BRCA
mutation, including 3 who had a somatic BRCA mutation. Five patients were BRCA
wild-type. One was found to have a RAD51B
mutation. Some patients had no homologous recombination repair (HRR) mutations and 1 patient tested negative for HRD results. One patient with germline BRCA
wild-type had no available tumor test results.
“That means that at least one-third of the patients deriving substantial long-term benefit from olaparib had BRCA
wild-type status,” said Gourley. “Patients who had both a negative tumor test result for mutations in HRR-associated genes and a negative Myriad HRD score were found within this group.”
Safety issues associated with olaparib and the drug’s tolerability profile were unchanged from previous studies.2
In March 2017, the FDA granted a priority review to a new drug application for olaparib as a maintenance therapy in relapsed patients with platinum-sensitive ovarian cancer.
- Gourley C, Friedlander M, Matalonis U, et al. Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC). J Clin Oncol 35, 2017 (suppl; abstr 5533).
- Ledermann JA, Harter P, Gourley C, et al. Overall survival (OS) in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy: An interim analysis. J Clin Oncol 34, 2016 (suppl; abstr 5501).