Patient-centered outcomes in the POLO study of active maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.

Abstract

BACKGROUND:

The phase 3 POLO study demonstrated a significant progression-free survival (PFS) benefit and preserved health-related quality of life (HRQOL) for active maintenance treatment with olaparib vs placebo in patients with metastatic pancreatic cancer and a germline BRCA mutation. Here, we present a post hoc analysis of the patient-centered outcomes: time without significant symptoms of disease progression or toxicity (TWiST) and quality-adjusted TWiST (Q-TWiST).

METHODS:

Patients were randomized 3:2 to maintenance olaparib (300 mg tablets twice daily) or placebo. Overall survival time was divided into TWiST, toxicity (TOX; time before disease progression with significant symptoms of toxicity), and relapse (REL; time after disease progression until death or censoring). Q-TWiST was the sum of TWiST, TOX, and REL, each weighted by HRQOL utility scores during the relevant health-state period. A base-case and three sensitivity analyses were performed using differing definitions of TOX.

RESULTS:

In total, 154 patients were randomized (olaparib, n = 92; placebo, n = 62). TWiST was significantly longer for olaparib than placebo in the base-case analysis (14.6 vs 7.1 months; 95% CI, 2.9-12.0; p = .001) and all sensitivity analyses. No statistically significant benefit for Q-TWiST was observed in the base-case analysis (18.4 vs 15.9 months; 95% CI, -1.1 to 6.1; p = .171) or the sensitivity analyses.

CONCLUSION:

These results support the previous findings that maintenance olaparib significantly improves PFS relative to placebo without compromising HRQOL and demonstrate that the clinically meaningful benefits of olaparib persist even when symptoms of toxicity are considered.

• Authors: Hedy L Kindler, Hyun Kyoo Yoo, Robert Hettle, Karen Y Cui, Seongjung Joo, Gershon Y Locker, Talia Golan
• Journal: Cancer (Cancer) Vol. 129 Issue 9 Pg. 1411-1418 (05 01 2023) ISSN: 1097-0142 [Electronic] United States
• PMID: 36811344 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 American Cancer Society.

Chemical References

• olaparib
• Phthalazines
• BRCA1 protein, human
• BRCA2 protein, human

Topics

• Female
• Humans
• Disease Progression
• Neoplasm Recurrence, Local (drug therapy)
• Ovarian Neoplasms (drug therapy)
• Pancreatic Neoplasms (drug therapy, genetics, pathology)
• Patient-Centered Care
• Phthalazines (adverse effects)
• Quality of Life