Abstract
Purpose: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer. Methods: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel. Results: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41–86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p =.935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43–1.14] p =.064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response. Conclusion: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.
Original language | English (US) |
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Pages (from-to) | 1234-1245 |
Number of pages | 12 |
Journal | Cancer |
Volume | 130 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2024 |
Keywords
- cediranib
- clinical trial
- endometrial cancer
- olaparib
- PARP inhibitor
ASJC Scopus subject areas
- Oncology
- Cancer Research