COSMIC-021: Cabozantinib–atezolizumab duo promising for mCRPC
medwireNews: The combination of cabozantinib and atezolizumab has antitumor activity and a manageable safety profile in men with metastatic castration-resistant prostate cancer (mCRPC), indicate preliminary trial data.
The interim results of the mCRPC cohort of the phase 1b COSMIC-021 study of cabozantinib plus atezolizumab in multiple advanced solid tumors were reported in a poster at the 2020 Genitourinary Cancers Symposium held in San Francisco, California, USA.
Neeraj Agarwal (Huntsman Cancer Institute, Salt Lake City, Utah, USA) and co-authors explained that treatment with either the multitargeted tyrosine kinase inhibitor cabozantinib or the PD-L1 inhibitor atezolizumab as single agents has achieved low objective response rates (ORRs) of 5% and 0%, respectively, in this patient population.
But “cabozantinib promotes an immune-permissive environment that may enhance response to immune checkpoint inhibitors,” they added.
And indeed, an objective response was attained by 32% of the 44 participants of the cohort. The overall disease control rate was 80%, comprising rates of 48% for stable disease, 27% for partial response, and 5% for complete response.. The median duration of response was 8.3 months.
The combined treatment appeared to have “consistent activity” in men with high-risk disease, with an ORR of 33% among the 36 patients who had visceral and/or extra-pelvic lymph node metastases, commented Agarwal and team.
The mCRPC cohort enrolled men who had developed radiographic progression after treatment with enzalutamide, abiraterone, or both. They could not have received prior cabozantinib, immunotherapy, or chemotherapy except for docetaxel for castration-sensitive disease. Participants received cabozantinib at a daily dose of 40 mg, while atezolizumab was given at a dose of 1200 mg every 3 weeks. At the time of the current analysis, patients had been followed up for a median of 12.6 months.
With regard to safety, the team noted that cabozantinib plus atezolizumab has “a tolerable safety profile.” Treatment-related adverse events (AEs) of grade 3 or 4 occurred in 59% of patients and immune-related AEs of grade 3 or 4 were observed in 9.1%.
The rate of discontinuation of both study drugs due to AEs was 6.8% and there was one treatment-related death due to dehydration in a 90-year-old patient with a history of failure to thrive.
In light of these results, the mCRPC cohort of the trial “is being further expanded” and a phase 3 trial of the combination in mCRPC is planned, concluded Agarwal and colleagues.
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