ASCO GU 2021: The Efficacy and Safety of Nivolumab Plus Docetaxel For Chemotherapy-Naïve mCRPC in the Final Analysis of the CheckMate 9KD Arm B Trial

( Docetaxel is a standard-of-care chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) patients that may potentiate antitumor immune responses, thus supporting its use in combination with nivolumab, which has shown limited antitumor activity in mCRPC as monotherapy. CheckMate 9KD (NCT03338790) is a phase 2 trial of nivolumab in combination with rucaparib, docetaxel, or enzalutamide for patients with mCRPC. An earlier interim analysis from CheckMate 9KD showed encouraging efficacy of the combination of nivolumab plus docetaxel with no new safety signals versus historical data with nivolumab and docetaxel alone. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) Dr. Karim Fizazi and colleagues presented the final analysis results for CheckMate 9KD Arm B (nivolumab plus docetaxel) of CheckMate 9KD.

CheckMate 9KD Arm B enrolled patients with chemotherapy-naive mCRPC with ongoing androgen deprivation therapy and ≤ 2 prior novel antiandrogen therapies (ie. abiraterone, enzalutamide, etc). Patients received nivolumab 360 mg plus docetaxel 75 mg/m2 Q3W plus prednisone 5 mg BID for ≤ 10 cycles, followed by nivolumab 480 mg Q4W until disease progression/unacceptable toxicity (for up to 2 years). The trial design is as follows:


The co-primary endpoints were objective response rate and PSA response rate (defined as a ≥ 50% PSA reduction). Secondary endpoints included radiographic progression-free survival, overall survival, and safety.

             Of 84 treated patients with a median age of 71 years (range: 53-88), 27% had visceral disease and 54% had measurable disease; median PSA was 49.5 ng/mL (range: 1.2-1085). The median number of docetaxel cycles was 8 (range: 1-10), and the median number of nivolumab doses was 11 (range: 1-27). Over a median follow up of 15.2 months, there were 76 patients (90.5%) that had discontinued therapy, most commonly secondary to disease progression (59.5%) and drug toxicity (17.9%). There was 1 (2.2%) complete objective response and 17 (37.8%) partial responses in 45 patients with measurable disease:


For the 18 patients with an objective response, the median time to response was 2.0 (range: 1.6-7.3) months, with a median duration of response of 7.0 months (95% CI 6.4-12.4). Among 81 PSA-evaluable patients, the median time to PSA progression was 8.7 months (95% CI 7.3-10.4). 

A reduction from baseline in the sum of diameters of target lesions was observed in most evaluable patients (79.5%), and the median change from baseline for all patients was -32.1%. Tumor reductions and PCWG3 responses were observed both in patients who had or had not previously received novel antiandrogen therapies:


A reduction from baseline in PSA was observed in most evaluable patients (84.0%) and median change from baseline for all patients was -54.6%. PSA reductions and responses were observed both in patients who had or had not previously received novel antiandrogen therapies:


The median radiographic progression free survival for all patients was 9.0 months (95% CI 8.0-11.6) and the median overall survival was 18.2 months (95% CI 14.6-20.7):


Any-grade treatment-related adverse events occurred in 95.2% of patients, most commonly fatigue (39.3%), diarrhea (35.7%), and alopecia (34.5%). Grade 3-4 treatment-related adverse events occurred in 47.6% of patients, most commonly neutropenia (16.7%); treatment-related adverse events led to discontinuation in 29.8% of patients. The most common immune-related adverse events were gastrointestinal (35.7%) or skin-related (26.2%). There were three treatment-related deaths, one pneumonitis related to nivolumab and two pneumonias related to docetaxel.

Dr. Fizazi concluded this final analysis of the CheckMate 9KD Arm B presentation with the following conclusions:

  • With longer follow-up, the combination of nivolumab plus docetaxel continued to show encouraging clinical activity in patients with mCRPC, with an objective response rate of 40% and confirmed PSA response of 47%
  • Notably, the antitumor effects of nivolumab plus docetaxel were apparent regardless of whether patients had received prior novel antiandrogen therapy
  • Additional biomarker analyses are ongoing to investigate potential markers of response to the combination of nivolumab plus docetaxel
  • There were no new safety signals reported with longer follow-up with nivolumab plus docetaxel
  • These results support further investigation of the combination of nivolumab plus docetaxel for patients with mCRPC inthe ongoing phase 3 CheckMate 7DX trial of nivolumab plus docetaxelversus placebo + docetaxel (NCT04100018)

Presented by: Karim Fizazi, MD, Ph.D., Head of the Department of Cancer Medicine at the Institut Gustave Roussy, Villejuif, France and Professor of Oncology at the University of Paris

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021