Details

Autor(en) / Beteiligte

• Kim, Joseph W
• McKay, Rana R
• Radke, Marc R
• Zhao, Shilin
• Taplin, Mary-Ellen
• Davis, Nancy B
• Monk, Paul
• Appleman, Leonard J
• Lara, Jr, Primo N
• Vaishampayan, Ulka N
• Zhang, Jingsong
• Paul, Asit K
• Bubley, Glenn
• Van Allen, Eliezer M
• Unlu, Serhan
• Huang, Ying
• Loda, Massimo
• Shapiro, Geoffrey I
• Glazer, Peter M
• LoRusso, Patricia M
• Ivy, S Percy
• Shyr, Yu
• Swisher, Elizabeth M
• Petrylak, Daniel P

Titel

Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984

Ist Teil von

• Journal of clinical oncology, 2023-02, Vol.41 (4), p.871-880

Ort / Verlag

United States: Wolters Kluwer Health

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer. Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) were randomly assigned 1:1 to arm A: cediranib 30 mg once daily plus olaparib 200 mg twice daily or arm B: olaparib 300 mg twice daily alone. The primary end point was radiographic progression-free survival (rPFS) in the intention-to-treat patients. The secondary end points were rPFS in patients with HRR-deficient and HRR-proficient mCRPC. In the intention-to-treat set of 90 patients, median rPFS was 8.5 (95% CI, 5.4 to 12.0) and 4.0 (95% CI, 3.2 to 8.5) months in arms A and B, respectively. Cediranib/olaparib significantly improved rPFS versus olaparib alone (hazard ratio [HR], 0.617; 95% CI, 0.392 to 0.969; = .0359). Descriptive analyses showed a median rPFS of 10.6 (95% CI, 5.9 to not assessed [NA]) and 3.8 (95% CI, 2.33 to NA) months (HR, 0.64; 95% CI, 0.272 to 1.504) among patients with HRR-deficient mCRPC, and 13.8 (95% CI, 3.3 to NA) and 11.3 (95% CI, 3.8 to NA) months (HR, 0.98; 95% CI, 0.321 to 2.988) among patients with -mutated mCRPC in arms A and B, respectively. The incidence of grades 3-4 adverse events was 61% and 18% in arms A and B, respectively. Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of grades 3-4 adverse events. -mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS.