TY - JOUR
T1 - Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer
T2 - results from the phase II CheckMate 9KD trial
AU - Fizazi, Karim
AU - González Mella, Pablo
AU - Castellano, Daniel
AU - Minatta, Jose N.
AU - Rezazadeh Kalebasty, Arash
AU - Shaffer, David
AU - Vázquez Limón, Juan C.
AU - Sánchez López, Héctor M.
AU - Armstrong, Andrew J.
AU - Horvath, Lisa
AU - Bastos, Diogo A.
AU - Amin, Neha P.
AU - Li, Jia
AU - Unsal-Kacmaz, Keziban
AU - Retz, Margitta
AU - Saad, Fred
AU - Petrylak, Daniel P.
AU - Pachynski, Russell K.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Background: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). Methods: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). Results: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7–55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7–58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0–11.6) and 18.2 (14.6–20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3–4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). Conclusions: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. ClinicalTrials.gov registration: NCT03338790.
AB - Background: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). Methods: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). Results: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7–55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7–58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0–11.6) and 18.2 (14.6–20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3–4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). Conclusions: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. ClinicalTrials.gov registration: NCT03338790.
KW - Clinical trial
KW - Docetaxel
KW - Metastatic castration-resistant prostate cancer
KW - Nivolumab
UR - http://www.scopus.com/inward/record.url?scp=85119369164&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.09.043
DO - 10.1016/j.ejca.2021.09.043
M3 - Article
C2 - 34802864
AN - SCOPUS:85119369164
SN - 0959-8049
VL - 160
SP - 61
EP - 71
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -