Maintenance Olaparib Yields Clinically Meaningful Benefits for Patients With Metastatic BRCA-Positive Pancreatic Cancer

A final analysis of the phase 3 POLO study found maintenance olaparib did not significantly improve overall survival (OS), however it did provide clinically meaningful benefits in time off chemotherapy and long-term survival for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation.

The multicenter, phase 3 trial enrolled 154 patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy between December 16, 2014 and January 15, 2019. Patients were randomized in a 3:2 ratio to either maintenance olaparib at 300 mg twice daily (n = 92) or placebo (n = 62).

The primary end point of the study was progression-free survival (PFS). Secondary end points included overall survival (OS), time to first subsequent therapy or death, time to second subsequent therapy or death, and time to study treatment discontinuation or death.

It was previously reported that treatment with olaparib resulted in statistically significant improvement of PFS when compared to placebo (7.4 months vs 3.8 months, respectively; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = .004).

Findings from this final analysis reported no statistically significant benefit in OS from olaparib (HR, 0.83; 95% CI, 0.56 to 1.22; P = .3487). The estimated 3-year OS rates were 33.9% for olaparib and 17.8% for placebo. However, median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30 to 0.66; P <.0001), time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89; P = .0111), and time to discontinuation of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63; P <.0001) all significantly favored olaparib. 

The study authors concluded, “although no statistically significant OS benefit was observed, the HR numerically favored olaparib, which also conferred clinically meaningful benefits including increased times off chemotherapy and long-term survival in a subset of patients.”

Sources:

Kindler HL, Hammel P, Reni M, et al. Overall survival results from the POLO trial: A phase III study of active maintenance olaparib versus placebo for germline BRCA-mutated metastatic pancreatic cancer. J Clin Oncol. Published online July 14, 2022. doi:10.1200/JCO.21.01604

Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381:317-327. doi:10.1056/NEJMoa1903387