medwireNews: Combining a PD-1 inhibitor with docetaxel could benefit chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC), suggest results from two early-phase trials.
The findings, presented at the 2021 Genitourinary Cancers Symposium, come from the multicohort phase 1b/2 KEYNOTE-365 and phase 2 CheckMate 9KD studies investigating pembrolizumab and nivolumab, respectively, in combination with other agents for mCRPC.
The current reports focus on the docetaxel cohorts, which in both trials included men who had not received prior chemotherapy for metastatic disease and had ongoing androgen deprivation therapy. The KEYNOTE-365 participants had received prior treatment with either abiraterone or enzalutamide, but not both, whereas the CheckMate 9KD patients could have received zero to two novel antiandrogen therapies.
Efficacy and safety of pembrolizumab–docetaxel
In cohort B of KEYNOTE-365, treatment with pembrolizumab 200 mg plus docetaxel 75 mg/m2 every 3 weeks alongside prednisone 5 mg twice daily led to a prostate-specific antigen (PSA) response (≥50% reduction) in 34% of the 103 participants, who were followed up for a median 32.4 months from enrollment.
The PSA response rates were 27.5% among the 51 men with RECIST measurable disease and 40.4% among the 52 with nonmeasurable disease. And the objective response rate (ORR), evaluated in those with measurable disease, was 23.1%, while the disease control rate in all patients was 76.0% and was a respective 73.1% and 78.8% in those with measurable and nonmeasurable disease.
Radiographic progression-free survival (PFS) was a median of 8.5 months in the full cohort and median overall survival (OS) was 20.2 months. The 12-month PFS and OS rates were 26.2% and 75.9%, respectively.
“The safety profile was consistent with the known profile of each agent,” said presenting author Leonard Appleman, from the University of Pittsburgh Medical Center in Pennsylvania, USA.
The most frequently observed treatment-related adverse events (TRAEs) of grade 3–5 were febrile neutropenia (11.5%) and anemia (4.8%), while the most common immune-mediated AEs of the same severity were pneumonitis (3.8%) and colitis (3.8%). Two cases of pneumonitis were fatal and deemed related to study treatment by the investigators.
“These results support further evaluation of pembrolizumab in combination with other agents for the treatment of metastatic CRPC in patients pretreated with abiraterone or enzalutamide,” commented Appleman.
“Docetaxel plus prednisone, with or without pembrolizumab, will be evaluated in a similar population of patients in the ongoing, randomized, phase 3 KEYNOTE-921 trial.”
Efficacy and safety of nivolumab–docetaxel
Presenting the final analysis of arm B of the CheckMate 9KD study, Karim Fizazi (Gustave Roussy, Villejuif, France) said that the cohort included 84 men who received nivolumab 360 mg plus docetaxel 75 mg/m2 every 3 weeks together with prednisone 5 mg twice a day.
Over a median follow-up of 15.2 months, a PSA response occurred in 46.9% of the 81 patients evaluable for PSA, while the ORR was 40% among the 45 patients with measurable disease. The PSA response rates for men who had versus had not previously received novel antiandrogens were 39.6% and 60.7%, respectively, and the corresponding ORRs were 38.7% and 42.9%.
The median radiographic PFS duration was 9.0 months in the total cohort, and was 8.5 and 12.0 months for patients with and without prior antiandrogen therapy, respectively. The corresponding median OS times were 18.2 months, 16.2 months, and unreached.
“The safety profile of the nivolumab plus docetaxel combination was mostly as expected based on prior monotherapy experiences,” said Fizazi.
He added, however, that the incidence of certain AEs with suspected immune etiology, such as rash, was “marginally higher than anticipated,” and immune-related AEs “will need to be closely monitored in future studies of this combination.”
Neutropenia was the most common TRAE of grade 3–4, observed in 16.7% of participants, followed by fatigue, diarrhea, and pneumonitis, each in 4.8%. Three deaths were attributed to the study drugs, one due to nivolumab-related pneumonitis and two due to docetaxel-related pneumonia.
“The results from this cohort support the ongoing CheckMate 7DX phase 3 trial of nivolumab plus docetaxel for metastatic CRPC,” concluded the presenter.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group