KEY TAKEAWAYS
- IMspire170 is a phase 3 trial aimed to assess the efficacy of the combination of cobimetinib and atezolizumab compared to pembrolizumab alone in patients diagnosed.
- The median PFS for the combination of cobimetinib and atezolizumab was 5.5 months, while 5.7 months (95% CI 3.7-9.6) for pembrolizumab alone.
- Exploratory biomarker analyses revealed that a higher tumor mutational burden was associated with enhanced clinical outcomes in both treatment groups.
Emerging medical data indicate that using MEK inhibitors with immunotherapeutic agents may enhance efficacy in treating melanoma. Researchers assessed the effectiveness of the combination of MEK inhibition and immune checkpoint inhibition compared to immune checkpoint inhibition alone in patients diagnosed with advanced melanoma that is BRAFV600 wild-type and has not been treated previously. IMspire170 was an international, randomized, open-label, phase III clinical trial. The participants were randomly assigned in a 1:1 ratio to receive cobimetinib (60 mg, administered on days 1-21) in combination with anti-programmed death ligand 1 atezolizumab (840 mg, administered every 2 weeks) in cycles lasting 28 days. Alternatively, they could receive anti-programmed death-1 pembrolizumab alone (200 mg, administered every 3 weeks) until they experienced a loss of clinical benefit, unacceptable toxicity, or chose to withdraw their consent.
The primary measure of interest was progression-free survival (PFS), evaluated by an independent review committee in the intention-to-treat cohort. From December 11, 2017, to January 29, 2019, 446 patients were randomly assigned to two treatment groups. The first group consisted of 222 patients who received cobimetinib in combination with atezolizumab, while the second group included 224 patients who received pembrolizumab. The median duration of follow-up was 7.1 months [interquartile range (IQR) 4.8-9.9] for the combination of cobimetinib and atezolizumab and 7.2 months (IQR 4.9-10.1) for pembrolizumab. The median progression-free survival (PFS) was 5.5 months [95% confidence interval (CI) 3.8-7.2] when treated with cobimetinib plus atezolizumab, compared to 5.7 months (95% CI 3.7-9.6) with pembrolizumab. The stratified hazard ratio was 1.15 (95% CI 0.88-1.50), and the P-value was 0.30. The hazard ratios for progression-free survival (PFS) demonstrated consistency across pre-defined subgroups. In the context of exploratory biomarker analyses, it was observed that a higher tumor mutational burden exhibited a correlation with enhanced clinical outcomes in both treatment groups.
The most prevalent grade 3-5 adverse events (AEs) observed were elevated blood creatine phosphokinase levels (10.0% with the combination of cobimetinib and atezolizumab compared to 0.9% with pembrolizumab), diarrhea (7.7% versus 1.9%), rash (6.8% versus 0.9%), high blood pressure (6.4% versus 3.7%), and acne-like skin inflammation (5.0% versus 0). Serious adverse events (AEs) were observed in 44.1% of patients receiving the combination of cobimetinib and atezolizumab, while 20.8% of patients receiving pembrolizumab experienced similar AEs. The variety of cobimetinib and atezolizumab did not improve progression-free survival (PFS) compared to pembrolizumab alone in individuals diagnosed with advanced melanoma lacking the BRAFV600 mutation.
Source: https://pubmed.ncbi.nlm.nih.gov/33309774/
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03273153
Gogas H, Dréno B, Larkin J, Demidov L, Stroyakovskiy D, Eroglu Z, Francesco Ferrucci P, Pigozzo J, Rutkowski P, Mackiewicz J, Rooney I, Voulgari A, Troutman S, Pitcher B, Guo Y, Yan Y, Castro M, Mulla S, Flaherty K, Arance A. Cobimetinib plus atezolizumab in BRAF V600 wild-type melanoma: primary results from the randomized phase III IMspire170 study. Ann Oncol. 2021 Mar;32(3):384-394. doi: 10.1016/j.annonc.2020.12.004. Epub 2020 Dec 10. PMID: 33309774.
