Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial

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). In the non-randomised, multicohort, global p...

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Published in:European journal of cancer (1990) 2022-01, Vol.160, p.61-71
Main Authors: Fizazi, Karim, González Mella, Pablo, Castellano, Daniel, Minatta, Jose N., Rezazadeh Kalebasty, Arash, Shaffer, David, Vázquez Limón, Juan C., Sánchez López, Héctor M., Armstrong, Andrew J., Horvath, Lisa, Bastos, Diogo A., Amin, Neha P., Li, Jia, Unsal-Kacmaz, Keziban, Retz, Margitta, Saad, Fred, Petrylak, Daniel P., Pachynski, Russell K.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antigens
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Castration
Chemotherapy
Clinical trial
Cohort Studies
Confidence intervals
Deprivation
Docetaxel
Docetaxel - pharmacology
Docetaxel - therapeutic use
Homologous recombination
Homology
Humans
Immunostimulation
Immunotherapy
Male
Metastases
Metastasis
Metastatic castration-resistant prostate cancer
Microenvironments
Middle Aged
Neutropenia
Nivolumab
Nivolumab - pharmacology
Nivolumab - therapeutic use
Patients
Pneumonitis
Prednisone
Prostate cancer
Prostate-specific antigen
Prostatic Neoplasms, Castration-Resistant - drug therapy
Response rates
Subpopulations
Survival
Tumor microenvironment
Tumors
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Summary: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). 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). 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). 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. NCT03338790. •Nivolumab plus docetaxel has clinical activity in men with chemotherapy-naïve metastatic castration-resistant prostate cancer.•Safety of the combination is consistent with that of the individual components.•These data support further investigation in the ongoing phase III CheckMate 7DX trial.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2021.09.043