KEY TAKEAWAYS
- This phase II, non-randomized, multicohort CheckMate 9KD trial involved 84 patients with mCRPC.
- The primary aim was to determine these patients’ ORR and the PSA50-RR of nivolumab and docetaxel combination therapy.
- Patients received nivolumab 360mg and docetaxel 75mg/m2 every 3 weeks with prednisone 5mg twice daily.
- The ORR was confirmed to be 40.0%, while the confirmed PSA50-RR was 46.9%. The median rPFS was 9.0 months, while the OS was 18.2 months.
- Patients with prior neoadjuvant hormonal therapy (NHT) had an ORR of 38.7% and a PSA50-RR of 39.6%, with a median rPFS of 8.5 months.
- The combination of nivolumab and docetaxel exhibited clinical efficacy in individuals with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).
The immunostimulatory effects of Docetaxel may facilitate an immunoresponsive microenvironment for prostate tumors, thereby justifying its combination with nivolumab, a programmed death-1 inhibitor, to treat metastatic castration-resistant prostate cancer (mCRPC). The non-randomized, multicohort, global phase II CheckMate 9KD trial involved 84 patients who had chemotherapy-naive mCRPC, ongoing androgen deprivation therapy, and had received ≤2 prior novel hormonal therapies (NHTs). These patients were administered nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles). Subsequently, they were given nivolumab 480 mg every 4 weeks (≤2 years). The co-primary endpoints comprised the objective response rate (ORR) and the prostate-specific antigen response rate (PSA50-RR), defined as a reduction of at least 50% from the baseline. The ORR (95% CI) was confirmed to be 40.0% (25.7-55.7), while the confirmed PSA50-RR (95% CI) was 46.9% (35.7-58.3).
The patient’s median radiographic progression-free survival (rPFS) with a 95% confidence interval was 9.0 months (8.0-11.6), while the overall survival (OS) was 18.2 months (14.6-20.7). In the subpopulations with and without prior neoadjuvant hormonal therapy (NHT), the overall response rate (ORR) was 38.7% and 42.9%, respectively. The prostate-specific antigen (PSA) 50 response rate (PSA50-RR) was 39.6% and 60.7%, respectively. The median radiographic progression-free survival (rPFS) was 8.5 months in the former group and 12.0 months in the latter group. The median overall survival (OS) was 16.2 months in the former group and not reached in the last group. The efficacy did not seem to be affected by the status of homologous recombination deficiency or tumor mutational burden. The prevalent treatment-associated adverse events of any grade and grade 3-4 were fatigue (39.3%) and neutropenia (16.7%), respectively. Three fatalities were associated with treatment, one attributed to nivolumab-induced pneumonitis, while the other two were linked to docetaxel-induced pneumonia. The combination of Nivolumab and Docetaxel exhibits clinical efficacy in individuals with chemotherapy-naïve metastatic castration-resistant prostate cancer. The safety profile was found to be consistent with the individual constituents.
Source:https://pubmed.ncbi.nlm.nih.gov/34802864/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03338790
Fizazi K, González Mella P, Castellano D, Minatta JN, Rezazadeh Kalebasty A, Shaffer D, Vázquez Limón JC, Sánchez López HM, Armstrong AJ, Horvath L, Bastos DA, Amin NP, Li J, Unsal-Kacmaz K, Retz M, Saad F, Petrylak DP, Pachynski RK. Nivolumab plus docetaxel in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II CheckMate 9KD trial. Eur J Cancer. 2022 Jan;160:61-71. doi: 10.1016/j.ejca.2021.09.043. Epub 2021 Nov 18. PMID: 34802864.
