IMblaze370: Atezolizumab With or Without Cobimetinib vs Regorafenib in Previously Treated Advanced Colorectal Cancer
In the phase III IMblaze370 trial reported in The Lancet Oncology, Eng et al found no survival benefit with third-line atezolizumab with or without cobimetinib vs regorafenib in patients with locally advanced or metastatic colorectal cancer.
Study Details
The open-label trial included 363 patients from 73 sites in 11 countries with unresectable locally advanced or metastatic colorectal cancer and disease progression on or intolerance to at least 2 previous systemic chemotherapy regimens. They were randomly assigned 2:1:1 between July 2016 and January 2017 to receive atezolizumab (840 mg every 2 weeks) plus cobimetinib (60 mg once daily for days 1–21 of a 28-day cycle; n = 183), atezolizumab (1,200 mg every 3 weeks; n = 90), or regorafenib (160 mg once daily for days 1–21 of a 28-day cycle; n = 90). Treatment was continued until loss of clinical benefit or unacceptable toxicity. Recruitment of patients with high microsatellite instability was capped at 5%; three patients each in the atezolizumab/cobimetinib group and atezolizumab group had known high microsatellite instability status.
The primary endpoint was overall survival in the intention-to-treat population.
Overall Survival
At data cutoff in March 2018, median follow-up was 7.3 months. Median overall survival was 8.87 months in the atezolizumab/cobimetinib group (hazard ratio [HR] vs regorafenib = 1.00, P = .99), 7.10 months in the atezolizumab group (HR vs regorafenib = 1.19, P = .34), and 8.51 months in the regorafenib group. Median progression-free survival was 1.91 months in the combination group, 1.94 months in the atezolizumab group, and 2.00 months in the regorafenib group.
Adverse Events
Grade 3 or 4 adverse events occurred in 61% of the combination group, 31% of the atezolizumab group, and 58% of the regorafenib group, with the most common in the combination group being diarrhea (11%), anemia (6%), increased creatine phosphokinase (7%), and fatigue (4%). Serious adverse events occurred in 40% of the combination group, 17% of the atezolizumab group, and 23% of the regorafenib group. Adverse events led to discontinuation of treatment in 21% of the combination group, 4% of the atezolizumab group, and 9% of the regorafenib group. Treatment-related death occurred in two patients in the combination group (due to sepsis) and one patient in the regorafenib group (due to intestinal perforation).
The investigators concluded, “IMblaze370 did not meet its primary endpoint of improved overall survival with atezolizumab plus cobimetinib or atezolizumab vs regorafenib. The safety of atezolizumab plus cobimetinib was consistent with those of the individual drugs. These results underscore the challenge of expanding the benefit of immunotherapy to patients whose tumors have lower baseline levels of immune inflammation, such as those with microsatellite-stable metastatic colorectal cancer.”
Fortunato Ciardiello, MD, of Universita degli Studi della Campania Luigi Vanvitelli, Naples, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by F. Hoffmann-La Roche Ltd./Genentech Inc. For full disclosures of the study authors, visit thelancet.com.
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