(UroToday.com) 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).