KEY TAKEAWAYS
- The study, COSMIC-021 (NCT03170960), aimed to assess the objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, as determined by the investigator.
- The study enrolled 132 eligible patients with metastatic castration-resistant prostate cancer with radiographic soft tissue progression following treatment with enzalutamide, abiraterone, or both.
- The study revealed that the ORR was 23%, with 3% confirmed complete and 21% verified partial responses.
Patients with metastatic castration-resistant prostate cancer have limited treatment options after undergoing novel hormonal therapy such as abiraterone or enzalutamide. The COSMIC-021 trial is an ongoing, multicentre, open-label, phase 1b study designed to assess the safety and efficacy of cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, in combination with atezolizumab, a Programmed Cell Death Ligand 1 (PD-L1) inhibitor, in patients with metastatic castration-resistant prostate cancer. The study included a dose-escalation stage followed by tumor-specific expansion stages and enrolled Expansion Cohort 6 at 42 cancer research centers across France, Italy, the Netherlands, Spain, and the USA.
Suitable patients were 18 years or older with radiographic soft tissue progression after undergoing treatment with either enzalutamide or abiraterone, or both. Patients had measurable quiet tissue disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received oral cabozantinib 40 mg per day and intravenous atezolizumab 1,200 mg once every three weeks, with treatment continuing until progressive disease or unacceptable toxicity. All enrolled patients were assessed for efficacy and safety, with the primary endpoint being the objective response rate per RECIST version 1.1 set by the investigator. The trial is registered with ClinicalTrials.gov, NCT03170960. Between April 24, 2018, and August 31, 2020, 132 patients with metastatic castration-resistant prostate cancer were enrolled in the COSMIC-021 study and received at least one dose of study treatment. At the time of data cutoff on February 19, 2021, the median duration of follow-up was 15.2 months (IQR 9·6-21·7). The investigator determined the objective response rate to be 23% (95% CI 17-32; 31 of 132 patients), with 28 (21%) verified partial responses and three (2%) confirmed complete responses. Among the 132 patients, 72 (55%) had grade 3-4 treatment-related adverse events, with the most common being pulmonary embolism (11 [8%] patients), diarrhea (9 [7%]), fatigue (9 [7%]), and hypertension (9 [7%]). Dehydration was one of one grade 5 treatment-related adverse events. Additionally, 74 (56%) of 132 patients had severe adverse events of any causality, and 28 (21%) of 132 patients had treatment-related adverse events leading to discontinuing either study drug. The study concluded the combination of cabozantinib and atezolizumab demonstrated promising antitumor activity in patients with metastatic castration-resistant prostate cancer who had undergone novel hormonal therapy with an acceptable safety profile. These results support further evaluating this combination as a possible treatment option for this patient population.
Source: https://pubmed.ncbi.nlm.nih.gov/35690072/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03170960
Agarwal N, McGregor B, Maughan BL, Dorff TB, Kelly W, Fang B, McKay RR, Singh P, Pagliaro L, Dreicer R, Srinivas S, Loriot Y, Vaishampayan U, Goel S, Curran D, Panneerselvam A, Schwickart M, Choueiri TK, Pal S. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: results from an expansion cohort of a multicentre, open-label, phase 1b trial (COSMIC-021). Lancet Oncol. 2022 Jul;23(7):899-909. doi: 10.1016/S1470-2045(22)00278-9. Epub 2022 Jun 9. PMID: 35690072.
