As reported in the Journal of Clinical Oncology by Hedy L. Kindler, MD, FASCO, and colleagues, the final overall survival analysis of the phase III POLO trial showed no significant difference between the maintenance olaparib group vs the placebo group in patients with germline BRCA-mutated metastatic pancreatic cancer. Long-term survival was more common in the olaparib group, and time to subsequent therapy was prolonged.
Hedy L. Kindler, MD, FASCO
The trial supported the December 2019 approval of olaparib in this setting on the basis of the primary analysis of progression-free survival.
Study Details
In the double-blind trial, 154 patients with disease that had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to maintenance olaparib at 300 mg twice daily (n = 92) or placebo (n = 62); treatment continued until radiologic disease progression or unacceptable toxicity. Overall survival was a secondary endpoint.
Key Findings
The median duration of follow-up for overall survival in censored patients was 31.3 months in the olaparib group (range = 0.3–63.5 months) and 23.9 months in the placebo group (range = 3.9–50.6 months).
Median overall survival was 19.0 months in the olaparib group vs 19.2 months in the placebo group (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.56–1.22, P = .3487). The Kaplan-Meier curves separated at approximately 24 months, with estimated 3-year overall survival rates of 33.9% vs 17.8%; at the time of analysis, 26 patients (28.3%) vs 11 patients (17.7%) remained alive.
At the time of analysis, 14.1% of patients in the olaparib group vs 3.2% in the placebo group were still receiving study treatment. Any subsequent therapy was received by 62.0% vs 87.1% of patients, with the most common second-line therapy being platinum-based chemotherapy. The range of subsequent therapies was two to six vs two to eight.
For other secondary endpoints, patients in the olaparib group had significant improvements in median time to first subsequent cancer therapy or death (HR = 0.44, 95% CI = 0.30–0.66, P < .0001), time to second subsequent cancer therapy or death (HR = 0.61, 95% CI = 0.42–0.89, P = .0111), and time to discontinuation of study treatment or death (HR = 0.43, 95% CI = 0.29–0.63, P < .0001), with a borderline significant improvement in median time to second disease progression or death (HR = 0.66, 95% CI = 0.43–1.02, P = .0613). Estimated 3-year first and second subsequent chemotherapy-free rates were 21.5% vs 3.6% and 23.4% vs 5.9%, respectively.
The investigators concluded, “Although no statistically significant overall survival benefit was observed, the hazard ratio numerically favored olaparib, which also conferred clinically meaningful benefits, including increased time off chemotherapy and long-term survival in a subset of patients.”
Hedy L. Kindler, MD, of the Section of Hematology/Oncology, University of Chicago, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a grant from the National Cancer Institute and by AstraZeneca, as part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co Inc. For full disclosures of the study authors, visit ascopubs.org.
