No survival benefit for olaparib in BRCA-mutated metastatic pancreatic cancer

Presented by

Prof. Talia Golan, Sheba Medical Center, Israel

Conference

ASCO GI 2021

Trial

Phase 3, POLO

Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer demonstrated improved outcomes for key primary endpoints, but failed to provide improved overall survival (OS) benefit.

Prof. Talia Golan (Sheba Medical Center, Israel) presented the OS data from the phase 3 POLO trial (NCT02184195) [1]. In this trial, patients with germline BRCA-mutated metastatic pancreatic cancer who had had not progressed on frontline platinum-based chemotherapy for at least 16 weeks were randomised to poly(ADP-ribose) polymerase (PARP) inhibitor olaparib or placebo as maintenance therapy. Previously published results demonstrated significantly improved median progression-free survival (PFS) favouring the olaparib arm of this trial [2]. In POLO, patients were randomised 3:2 olaparib (300 mg tablet twice daily; n=92) or placebo (n=62). OS was a key secondary endpoint. Dr Golan presented the updated findings of the primary analysis of OS after 108 deaths. Though patients were not permitted to cross over, patients in the placebo arm were eventually treated with olaparib.

With a median follow-up of 31.3 and 23.9 months for the olaparib and placebo arms, respectively, median OS was 19.0 months with olaparib and 19.2 months with placebo (HR 0.83; 95% CI 0.56-1.22; P=0.3487). OS at 36 months was 33.9% for olaparib and 17.8% for placebo. The time from randomisation to second disease progression or death (PFS2) was 16.9 months for olaparib compared with 9.3 months for the placebo group (HR 0.66; 95% CI 0.43–1.02; P=0.0613). The time to discontinuation of treatment was significantly different between the 2 arms (7.5 months for olaparib vs 3.8 months for placebo; HR 0.43; 95% CI 0.29-0.63; P<0.0001).

Safety signals were consistent with previous reports of olaparib, with the most common being anaemia, hyperglycaemia, or upper abdominal pain. Treatment discontinuation attributable to adverse events occurred in 8.9% patients taking olaparib compared with 1.6% taking placebo.

In conclusion, there was no statistically significant difference concerning OS for olaparib maintenance treatment for patients with germline BRCA-mutated metastatic pancreatic cancer whose disease had not progressed during platinum-based chemotherapy.

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