KEY TAKEAWAYS
- Phase III of KEYNOTE-921 evaluated the safety and efficacy of pembrolizumab + docetaxel as treatment following disease progression on a next-generation hormonal agent (NHA).
- Patients were randomly grouped into two, one receiving Placebo with docetaxel and the other receiving pembrolizumab + docetaxel.
- Pembrolizumab + docetaxel proved superior in the primary and secondary parameters of the trial.
- The most reported AEs were pneumonitis and hypothyroidism.
The effectiveness and safety of pembrolizumab + docetaxel vs. placebo + docetaxel in patients with mCRPC who had previously gotten NHA therapy were compared in the randomized, double-blind, phase 3 KEYNOTE-921 trial. Participants were randomly assigned to receive either 200 mg of pembrolizumab Q3W or a placebo for 35 cycles (about two years) and 10 cycles of 75 mg/m2 docetaxel Q3W and 5 milligrams of prednisone BID.
The main endpoints were overall survival (OS) and radiographic progression-free survival (rPFS; tested at first interim analysis), according to PCWG-modified RECIST 1.1. (OS; tested at final analysis). 1030 patients were randomly assigned to receive saline + docetaxel (n=515) or pembrolizumab + docetaxel (n=515).
The final analysis’s median (interquartile range) period from randomization to the data cutoff date of June 20, 2022, was 22.7 months (12.1–36.7). Baseline characteristics were fairly evenly distributed between the arms; roughly 50% of the participants in each arm had previously taken abiraterone.
rPFS and OS were the two main endpoints that were not met (median 8.6 months with pembrolizumab plus docetaxel vs. 8.3 months with placebo plus docetaxel; HR 0.85, 95% CI 0.71-1.00; P=0.0335). The median TFST was 10.7 months compared to 10.4 months (HR 0.86, 95% CI 0.74–1.01). In comparison to placebo + docetaxel, treatment-related adverse events (AEs) happened in 94.6% (grade 3 in 43.2%) and 94.9% (grade 3 in 36.6%) of patients, respectively. When comparing pembrolizumab + docetaxel to placebo + docetaxel, patients experienced immune-mediated adverse events (AEs) and infusion reactions in 23.3% (grade 3 in 6.2%) and 12.3% (grade 3 in 1.2%) of cases, respectively. The most prevalent AEs were pneumonitis and hypothyroidism.
Pembrolizumab was added to docetaxel, but this did not result in a noticeably higher rate of treatment-related adverse events (AEs) or a substantial improvement in rPFS or OS for patients with mCRPC.
Source: https://meetings.asco.org/abstracts-presentations/217325
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03834506
Petrylak, D. P., Ratta, R., Matsubara, N., Korbenfeld, E. P., Gafanov, R., Mourey, L., Todenhöfer, T., Gurney, H., Kramer, G., Bergman, A. M., Zalewski, P., Santis, M. D., Armstrong, A. J., Gerritsen, W. R., Pachynski, R. K., Byun, S. S., Li, X. T., Schloss, C., Poehlein, C. H. & Fizazi, K. (2023). J Clin Oncol 41, 2023 (suppl 6; abstr 19) DOI: 10.1200/JCO.2023.41.6_suppl.19
