KEY TAKEAWAYS
- The phase 3 POLO trial evaluated the efficacy of maintenance treatment with olaparib compared to placebo in patients with metastatic pancreatic cancer and a germline BRCA mutation.
- The study involved randomization of patients in a 3:2 ratio to receive either olaparib or placebo, with three distinct clinical outcomes measured: TWiST, TOX, REL.
- The study found that olaparib significantly prolonged TWiST compared to the placebo, with 14.6 months for olaparib and 7.1 months for the placebo.
- A total of 154 patients were randomly assigned, with 92 receiving olaparib and 62 receiving placebo.
- The Q-TWiST did not show a statistically significant advantage for olaparib over the placebo.
The phase 3 POLO study results indicate that active maintenance treatment with olaparib significantly benefits progression-free survival (PFS) and preserves the health-related quality of life (HRQOL) for patients with metastatic pancreatic cancer and a germline BRCA mutation, compared to placebo. This report presents a retrospective examination of the patient-centered outcomes, precisely the duration without notable disease progression or toxicity, also known as TWiST, and the quality-adjusted TWiST, or Q-TWiST.
The study involved a randomization process where patients were assigned in a 3:2 ratio to receive either maintenance olaparib (300 mg tablets administered twice daily) or a placebo. The survival duration was partitioned into three distinct clinical outcomes: Time Without Symptoms of Disease or Toxicity (TWiST), Time Before Disease Progression with significant symptoms of toxicity (TOX), and Time After Disease Progression until death or censoring (REL). The Q-TWiST metric was calculated by combining the Time Without Symptoms and Toxicity, Time with Toxicity, and Time with Relapse scores. Each score was adjusted by the Health-Related Quality of Life utility scores during the corresponding health state period. A baseline analysis and three sensitivity analyses were conducted utilizing varying definitions of toxicity.
A total of 154 patients were randomly assigned, with 92 receiving olaparib and 62 receiving placebo. The Time Without Symptoms or Toxicity was significantly longer for olaparib than placebo in the base-case analysis, with 14.6 months for olaparib and 7.1 months for placebo (95% confidence interval, 2.9-12.0; P= .001). This finding was consistent across all sensitivity analyses conducted. The base-case analysis and sensitivity analyses did not reveal any statistically significant advantage for Q-TWiST (Quality-Adjusted Time Without Symptoms of disease and Toxicity of treatment) (18.4 vs. 15.9 months; 95% CI, −1.1 to 6.1; P = .171). The outcomes above corroborate the prior discoveries that the sustained use of olaparib substantially enhances progression-free survival compared to maintaining the health-related quality of life. Furthermore, the results indicate that the advantageous effects of olaparib remain clinically significant even when the adverse effects are considered.
Source:https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/cncr.34610
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02184195
Hedy L. Kindler, Hyun Kyoo Yoo, Robert Hettle MMath, Karen Y. Cui, Seongjung Joo, Gershon Y. Locker, Talia Golan/Patient-centered outcomes in the POLO study of active maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer/Cancer, 129(9), 1411–1418. https://doi.org/10.1002/cncr.34610
