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Combining Tyrosine Kinase and PD-L1 Inhibitors to Treat Metastatic Prostate Cancer

By: Vanessa A. Carter, BS
Posted: Tuesday, August 30, 2022

The phase Ib COSMIC-021 trial, performed by Neeraj Agarwal, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues assessed the combination of the tyrosine kinase inhibitor cabozantinib and the PD-L1 inhibitor atezolizumab in patients with metastatic castration-resistant prostate cancer. Published in The Lancet Oncology, these data support the use and further evaluation of this combination therapy in this patient population.

“Cabozantinib plus atezolizumab showed promising antitumor activity in patients with metastatic castration-resistant prostate cancer after novel hormonal therapy with an acceptable safety profile,” concluded the investigators. “Further evaluation of this combination therapy is ongoing in the randomized phase III CONTACT-02 study (ClinicalTrials.gov identifier NCT04446117) of cabozantinib with atezolizumab compared with second novel hormonal therapy in [these] patients.”

This open-label, multicenter study enrolled 132 patients with metastatic castration-resistant prostate cancer who demonstrated radiographic soft-tissue disease progression following prior treatment. Participants were administered 40 mg/day of oral cabozantinib along with 1,200 mg of intravenous atezolizumab every 3 weeks. Study treatment continued until unacceptable toxicity or disease progression.

Visceral metastases (n = 42) or measurable extrapelvic lymphadenopathy (n = 79) was observed in 101 patients; the remaining 31 participants had soft-tissue metastasis or measurable pelvic adenopathy. The median time from most recent systemic therapy was 1.3 months, and the median follow-up was 15.2 months. With 28 confirmed partial responses and 3 confirmed complete responses, the objective response rate was 23%.

A total of 55% of individuals experienced grade 3 or 4 treatment-related adverse events, most commonly pulmonary embolism (8%), hypertension (7%), fatigue (7%), and diarrhea (7%). Of note, there was one event of grade 5 dehydration, which was thought to be related to treatment. Approximately 56% of patients had serious adverse events of any grade, and 21% of individuals discontinued study treatment because of treatment-related adverse events.

Disclosure: For full disclosures of the study authors, visit thelancet.com.


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