Disease Control With Cabozantinib Plus Atezolizumab in CRPC

For previously treated patients with locally advanced or metastatic castration-resistant prostate cancer (CRPC), cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) continued to show clinically significant activity, according to results from the phase Ib COSMIC-021 trial, presented during the European Society for Medical Oncology virtual meeting.

In this exclusive MedPage Today video, Yung Lyou, MD, PhD, a medical oncologist at City of Hope in Duarte, California, briefly describes the study and his clinical takeaways.

Following is a transcript of his remarks:

Hi, my name is Dr. Yung Lyou. I am an assistant clinical professor at City of Hope specializing in general urinary cancers, and I am a medical oncologist. So the study I wanted to talk about today is cohort 6 of the COSMIC-21 study, which is a phase Ib study looking at the combination of cabozantinib, which is a tyrosine kinase inhibitor [TKI], combined with atezolizumab, which is an immune checkpoint inhibitor, and seeing how patients with metastatic prostate cancer responded to this particular treatment.

One of the key reasons this study was of particular interest is that it is one of the first studies, or one of the few studies out there, that shows efficacy and metastatic castration-resistant prostate cancer combining a TKI and an IO [immuno-oncology] agent.

The way this study was conducted is that they recruited patients that had radiographic progression in soft tissue after getting an anti-androgen such as enzalutamide and/or abiraterone prednisone. And the other key algebra criteria had to be that the patients had measurable disease based on RECIST 1.1 in the soft tissues, or extrapelvic lymph nodes, and prior chemotherapy was not permitted with the exception of docetaxel for metastatic castration-sensitive prostate cancer.

So for this clinical trial, a total of 132 patients were enrolled, and 101 of them had visceral and extrapelvic lymph nodes. And all of these patients were metastatic castration-resistant prostate cancer patients. And what this showed was that the treatment of combined cabozantinib and atezolizumab showed significant efficacy with the overall response rate, including all partial responses of 15%, where they had a pretty significant disease control rate — which includes CR [complete response], PR [partial response], and SD [stable disease] patients — of 84%.

Furthermore, what was also noticed from this study was that the overall adverse effects were tolerable with having only 20% of patients discontinue, and the adverse effects themselves were consistent with what was expected from administering these agents separately, such as diarrhea, fatigue, and some IRAEs [immune-related adverse events] such as dermatitis and hand-foot syndrome, which comes from the use of cabozantinib.

So the key take-homes I would like to say from this particular study is that it is significant, and that it shows that combining non-cytotoxic chemotherapy for metastatic castration-resistant prostate cancer patients using a TKI and IO agent is beneficial.

And in this phase I study, there was good safety signals and also meaningful clinical responses. And the investigators now are further investigating to see if this combination is effective in a larger phase III study, which is the CONTACT-02 study.