The following is a summary of “Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer” published in the December 2022 issue of Oncology by Kindler et al.
According to the phase III POLO research, individuals with metastatic pancreatic cancer with a germline BRCA mutation had a significant progression-free survival (PFS) and outlived placebo ones in favor of active olaparib maintenance treatment. For a study, researchers sought to provide the results of the study of secondary endpoints and overall survival (OS).
Patients were randomly allocated 3:2, either active maintenance olaparib (300 mg twice daily) or placebo if they had a deleterious or suspected harmful germline BRCA mutation and their cancer had not progressed after ≥16 weeks of first-line platinum-based chemotherapy. PFS was the major endpoint, with OS, time to second disease progression or death, time to first and second cancer therapy or death, time to study treatment termination or death, and safety and tolerability as supplementary end factors.
Olaparib was given to 92 individuals and a placebo to 62 others, for 154 patients. There was no statistically significant improvement in OS (median 19.0 v 19.2 months; HR, 0.83; 95% CI, 0.56 to 1.22; P =.3487). At almost 24 months, the Kaplan-Meier OS curves diverged, and the projected 3-year survival following random assignment was 33.9% v 17.8%, respectively. Time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89; P =.0111), time to termination of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63; P< .0001), and time to first subsequent cancer therapy or death all substantially favored olaparib. Without being statistically significant, the HR for second illness progression or death preferred olaparib (HR, 0.66; 95% CI, 0.43 to 1.02; P =.0613). Olaparib was well accepted and did not trigger any additional safety warnings.
Olaparib provided clinically significant benefits, including longer time off chemotherapy and long-term survival in a subset of patients, even though no statistically significant OS benefit was seen. The HR numerically favored olaparib.