Treatment with cabozantinib (Cabometyx), a kinase inhibitor, plus atezolizumab (Tecentriq), a PD-L1 inhibitor, led to clinically meaningful activity in men with metastatic castration-resistant prostate cancer (CRPC), including those with high-risk clinical features, according to the results of the phase 1b COSMIC-021 trial.
“The combination of cabozantinib and atezolizumab demonstrated a tolerable safety profile and clinically meaningful activity in men with metastatic CRPC,” said lead investigator Neeraj Agarwal, MD, MBBS, Director, Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah, Salt Lake City.
“The combination treatment was associated with an increase in the number of activated cytotoxic T-cells with concomitant decrease in immunosuppressive cells in peripheral blood,” Dr Agarwal noted. “Preliminary data do not suggest an association between PD-L1 expression and antitumor activity.”
The cohort with metastatic CRPC “is being further expanded, and cohorts evaluating the contribution of cabozantinib and atezolizumab have been initiated. Further evaluation of cabozantinib and atezolizumab in metastatic CRPC in a phase 3 trial is planned,” he added.
COSMIC-021 Trial Results
The multicenter, open-label, phase 1b COSMIC-021 clinical trial is evaluating the combination of atezolizumab and cabozantinib in patients with locally advanced or metastatic solid tumors. At the ASCO 2020 virtual meeting, Dr Agarwal reported data on the first 44 patients enrolled in the metastatic CRPC cohort. Previous treatment with docetaxel was allowed for patients with hormone-sensitive disease.
A total of 25 (57%) patients had a Gleason score of ≥8 at diagnosis. Moreover, 12 (27%) patients received previous treatment with docetaxel for metastatic castration-sensitive disease, and all 44 patients had received previous novel hormonal therapy.
In the 44 patients with metastatic CRPC who received the combination of cabozantinib and atezolizumab, the overall response rate (ORR) was 32%, with 3 complete responses and 11 partial responses. A total of 21 patients had stable disease, 8 patients had progressive disease, and the data were unavailable for 1 patient. The disease control rate was 80%.
In a subgroup of 36 patients with high-risk features, the ORR was 33%. The median time to response was 1.6 months (range, 1-7 months), and the median duration of response was 8.3 months (range, 2.8-12.5+ months).
The median follow-up was 15.8 months (range, 9-23 months). A total of 36 (82%) patients had high-risk metastatic CRPC. In addition, 15 (34%) patients had visceral metastases and 27 (61%) patients had extrapelvic lymph node metastases.
Grade 3/4 adverse events (AEs) occurred in 59% of patients. Grade 3/4 treatment-related AEs that occurred in ≥5% of patients included fatigue, diarrhea, and hyponatremia (7% each). Grade 3/4 immune-related AEs occurred in 4 patients, and AEs led to dose reductions of cabozantinib in 19 patients. Treatment discontinuation unrelated to the study drugs was reported in 4 patients. There was 1 treatment-related grade 5 AE of dehydration.