Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: a phase II, open-label,
E Sherman1, J L Lee2, P R Debruyne3
1Memorial Sloan Kettering Cancer Center, Head and Neck Oncology Service, New York, USA.
Background:
Although introduction of immune checkpoint inhibitors has revolutionized the treatment of cancer, their response rates are generally low. Preclinical and early phase clinical data suggest that MEK inhibition may sensitize tumors to immune checkpoint inhibitors by upregulating tumor antigen expression, programmed death-ligand 1 (PD-L1) expression, and tumor T-cell infiltration. We evaluated the efficacy and safety of cobimetinib plus atezolizumab in patients with advanced solid tumors in the open-label, multicohort phase II COTEST study.
Patients And Methods:
This analysis of the COTEST trial included patients from cohorts 1-4 [1-3: anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment-naive patients; 4: patients with disease progression on anti-PD-1/anti-PD-L1 treatment] who received cobimetinib 60 mg once daily for the first 21 days and intravenous infusions of atezolizumab 840 mg on days 1 and 15 of each 28-day cycle. Efficacy endpoints included objective response rate, overall survival, progression-free survival (PFS), and disease control rate.
Results:
Overall, 77 patients were enrolled in cohorts 1-4 (78% male; median age 62.8 years). Objective response rate was 20% in cohort 1 [squamous cell carcinoma of the head and neck (SCCHN)], 30% in cohort 2 (urothelial carcinoma), and 18% in cohort 3 (renal cell carcinoma); there were no responders among 20 patients in cohort 4 (SCCHN). The disease control rates in cohorts 1-4 were 50%, 40%, 24%, and 25%, respectively. The median PFS was 5.5, 3.4, 3.4, and 3.6 months in cohorts 1-4, respectively, and the median overall survival was 16.8, 18.7, 21.7, and 7.7 months, respectively. Most adverse events were of grade 1/2 and were manageable.
Conclusions:
Cobimetinib plus atezolizumab had moderate activity in patients with anti-PD-1/PD-L1 treatment-naive SCCHN and urothelial carcinoma, and weak activity in anti-PD-1/PD-L1 treatment-naive renal cell carcinoma, and no activity in checkpoint inhibitor-treated patients.
Insights
Cobimetinib plus atezolizumab showed moderate efficacy in treatment-naive head and neck, and urothelial cancers, but limited benefit in renal cell carcinoma and no benefit in patients previously treated with immune checkpoint inhibitors.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Treatment
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but have limited response rates.
- MEK inhibition may enhance ICI efficacy by increasing tumor antigen and PD-L1 expression, and T-cell infiltration.
- The COTEST study investigated the combination of cobimetinib and atezolizumab in advanced solid tumors.
Purpose of the Study:
- To evaluate the efficacy and safety of combining cobimetinib (a MEK inhibitor) with atezolizumab (an ICI) in patients with advanced solid tumors.
- To assess response rates, overall survival, and progression-free survival in different cancer types and treatment histories.
Main Methods:
- An open-label, multicohort Phase II COTEST study.
- Patients received cobimetinib (60 mg daily for 21 days) and atezolizumab (840 mg intravenously on days 1 and 15 of each 28-day cycle).
- Included treatment-naive patients with squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma, renal cell carcinoma, and patients with disease progression on prior ICIs.
Main Results:
- Objective response rates were 20% (SCCHN), 30% (urothelial), and 18% (renal cell) in treatment-naive cohorts.
- No responses were observed in patients previously treated with ICIs (n=20).
- Disease control rates ranged from 24-50% in treatment-naive groups, with median PFS of 3.4-5.5 months and median OS of 7.7-21.7 months.
Conclusions:
- Cobimetinib plus atezolizumab demonstrated moderate activity in treatment-naive SCCHN and urothelial carcinoma.
- The combination showed weak activity in treatment-naive renal cell carcinoma and no activity in patients previously treated with checkpoint inhibitors.
- Adverse events were generally manageable, mostly grade 1/2.
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