ESMO 2021: Cabozantinib in Combination With Atezolizumab in Patients With Metastatic Castration-Resistant Prostate Cancer: Results of Expanded Cohort 6 of the COSMIC-021 Study

( In the Proffered Paper Session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on prostate cancer, Dr. Neeraj Agarwal presented results of the COSMIC-021 cohort 6, examining the role of cabozantinib and atezolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC).

Dr. Agarwal began by emphasizing that cabozantinib, a tyrosine kinase inhibitor acting on MET, VEGF-R, and TAM family kinases, may promote an immune-permissive microenvironment and thus enhance response to immune checkpoint inhibitors. COSMIC-S021 (NCT03170960) is a multinational phase 1b study evaluating the role of cabozantinib + atezolizumab in solid tumors, including mCRPC. He reported efficacy and safety results of expanded cohort 6 in mCRPC among patients previously treated with enzalutamide or abiraterone.

To summarize COSMIC-021, patients were eligible if they have evidence of measurable disease, radiographic progression in soft tissue after enzalutamide and/or abiraterone, and ECOG performance status of 0 or 1. Notably, prior chemotherapy was not permitted apart for metastatic castration-sensitive prostate cancer (mCSPC) which was allowed. Following enrollment, patients received cabozantinib 40 mg PO QD and atezolizumab 1200 mg IV Q3W. Patients underwent imaging with CT/MRI scans every 6 weeks for 1 year and then every 12 weeks thereafter. The primary endpoint was ORR by investigator assessment per RECIST 1.1. Secondary endpoints included safety, PFS, and OS.



With a data cutoff of 19 Feb 2021, 132 patients with mCRPC were enrolled with a median (range) follow-up of 15.2 mo (5.7, 33.9). The median age was 70 years at the time of enrollment. Further, 68 (52%) had ECOG PS 0. In terms of disease burden, 101 (77%) had measurable visceral metastases and/or extrapelvic lymphadenopathy (EPLN) of whom 42 (32%) had visceral metastasis and 79 (60%) had EPLN. Additionally, 33 (25%) had previously received docetaxel for mCSPC, and 59 (45%) had received ≥2 prior NHT.

In terms of the primary endpoint, the ORR by investigator report among all patients per RECIST 1.1 was 23% with 3 CRs; ORR by independent review (BIRC) was 15% (all PRs). The disease control rate (CR + PR + SD) was 84% by investigator review and 81% by BIRC.


Among those patients with visceral metastasis and/or EPLN, the ORR by investigator review was 27% with 2 CRs and 18% by BIRC (all PRs). Further, the disease control rate was 88% by investigator review and 84% by BIRC. Further, the median PFS per RECIST 1.1 by BIRC was 5.7 months in all patients and 6.8 months among those with visceral metastasis and/or EPLN. In both groups, the median OS was 18.4 months.


Further, 47% of patients had a PSA decrease, and 23% achieved a 50% decrease or greater. Preliminary data do not suggest an association between tumor PD-L1 status (known for 75 patients) and anti-tumor activity.

On therapy, frequently observed treatment-related adverse events (TRAEs) were diarrhea (55%), nausea (42%), fatigue (43%), and decreased appetite (34%). Grade 3 or 4 TRAEs occurred in 55% of patients and one grade 5 TRAE of dehydration was reported. 43% of patients required dose reductions in cabozantinib and the same number required dose delays in atezolizumab.


In terms of immune-related adverse events of special interest, 66% of patients had any grade events and 20% had grade 3 or 4 adverse events of special interest.

In conclusion, Dr. Agarwal highlighted that these data from Cohort 6 of COSMIC-021 demonstrate that cabozantinib + atezolizumab has clinically meaningful activity with a manageable safety profile in mCRPC, supporting a phase 3 study of cabozantinib + atezolizumab A versus second NHT (CONTACT-02; NCT04446117).

Presented by: Neeraj Agarwal, MD Professor of Medicine, and a Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute (HCI), University of Utah. He also directs the Genitourinary Oncology Program and the Center of Investigational Therapeutics (CIT) at the HCI, Salt Lake City, Utah, United States of America