As reported in The Lancet Oncology by Neeraj Agarwal, MD, and colleagues, findings in the expansion cohort of the phase Ib COSMIC-021 trial indicate activity of the combination of cabozantinib and atezolizumab in patients with metastatic castration-resistant prostate cancer whose disease progressed after treatment with enzalutamide or abiraterone.

Neeraj Agarwal, MD

Study Details

The expansion cohort consisted of 132 patients enrolled at sites in France, Italy, the Netherlands, Spain, and the United States between April 2018 and August 2020. Patients received cabozantinib at 40 mg per day and atezolizumab at 1,200 mg once every 3 weeks, with treatment continuing until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate.

Responses

At data cutoff in February 2021, median follow-up was 15.2 months (interquartile range [IQR] = 9.6–21.7 months). Objective response was observed in 31 (23%, 95% confidence interval [CI] = 17%–32%) of 132 patients, including complete response in 3 (2%). Stable disease was observed in an additional 80 patients (61%), with a disease control rate of 84%. Median duration of response was 8.3 months (IQR = 4.6–11.0 months). No correlation between PD-L1 status and response was observed.

Among 101 patients with visceral metastases or measurable extrapelvic lymphadenopathy at baseline, objective response was observed in 27 (27%, 95% CI = 18%–37%), with complete response in 2 (2%). Median duration of response was 6.9 months (IQR = 4.2–9.8 months).

Median progression-free survival was 5.5 months (95% CI = 4.3–6.6 months), with a 1-year rate of 21%. Median overall survival was 18.4 months (95% CI = 14.3–24.7 months), with a 1-year rate of 68%.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 72 patients (55%), with the most common being pulmonary embolism (8%), diarrhea (7%), fatigue (7%), and hypertension (7%). Serious adverse events occurred in 74 patients (56%). Treatment-related adverse events led to discontinuation of any study drug in 28 patients (21%). The most common grade 3 or 4 immune-mediated adverse events were pancreatitis (6%) and hepatitis (5%). One treatment-related death was observed, due to dehydration.

The investigators concluded, “Cabozantinib plus atezolizumab showed promising antitumor activity in patients with metastatic castration-resistant prostate cancer after novel hormonal therapy with an acceptable safety profile, supporting further evaluation of this combination.”

Dr. Agarwal, of Huntsman Cancer Institute, University of Utah, Salt Lake City, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Exelixis. For full disclosures of the study authors, visit thelancet.com.