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Atezolizumab +/- cobimetinib vs regorafenib for previously treated metastatic colorectal cancer (IMblaze370)
By: Stijn van den Borne, MSc | Last updated: 22nd April 2019 | In: Gastrointestinal Cancer, ImmunoOncology, Immunotherapy, Oncology, Targeted Therapies
atezolizumab, Bayer, chemotherapy, cobimetinib, colorectal cancer, Exelixis, Genentech, Immunotherapy, mCRC, Oncology, PD-1, PD-L1, regorafenib, Roche, Tecentriq
Combining programmed death 1 ligand (PD-L1) inhibitor atezolizumab with MEK-inhibitor cobimetinib in patients with previously treated metastatic colorectal cancer (mCRC) does not improve the overall survival (OS) when compared to regorafenib, as was reported by the investigators of the IMblaze370 (NCT02788279) trial in the Lancet Oncology.1Eng C. et al. Lancet Oncol. 2019. doi: 10.1016/S1470-2045(19)30027-0.
The phase 3, open-label, multicentre, randomised, three-arm IMblaze370 study investigated the combination of atezolizumab plus cobimetinib vs atezolizumab vs regorafenib in the third-line treatment setting of adult patients with unresectable locally advanced or metastatic colorectal cancer. Eligible patients had a baseline ECOG performance status of 0-1 and experienced disease progression or intolerance on at least two previous lines of systemic chemotherapy. The majority of patients had microsatellite stable disease, the recruitment of microsatellite instability (MSI)-high patients was capped at 5%. Finally, participants were stratified for the extended RAS status (wild-type vs mutant) and the time since diagnosis of first metastasis (<18 months vs ≥18 months).
The primary efficacy endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Patients who received at least one dose of their assigned study drug were included in the safety assessment.
A total of 363 patients were randomised to receive atezolizumab 840 mg intravenously (IV) every 2 weeks (q2wk) plus cobimetinib 60 mg orally (p.o.) once daily (q.d.) on days 1-21 in 28-day cycles (N=183), single-agent atezolizumab 1200 mg IV q3wk (N=90), or regorafenib 160 mg p.o. q.d. on days 1-21 in 28-day cycles (N=90).
At a median follow-up of 7.3 months (interquartile range [IQR], 3.7-13.6) the median OS measured 8.87 months (95% confidence interval [CI], 7.00-10.61) in the group of patients treated with atezolizumab plus cobimetinib. In the atezolizumab and regorafenib groups, the median OS measured 7.10 months (95% CI, 6.05-10.05) and 8.51 months (95% CI, 6.41-10.71), respectively. The hazard ratio (HR) for the anti-PD-L1 plus MEK inhibitor vs regorafenib monotherapy was 1.00 (95% CI, 0.73-1.38; P=0.99). When comparing single-agent atezolizumab with regorafenib the HR was 1.19 (95% CI, 0.83-1.71; P=0.34).
Grade 3-4 adverse events (AEs) occurred in 61% (109/179) of patients treated with atezolizumab plus cobimetinib. In the atezolizumab and regorafenib groups, grade 3-4 AEs were reported in 31% (28/90) and 58% (46/80) of patients, respectively. Common all-cause grade 3-4 AEs in the combination group included diarrhoea (11%), anaemia (6%), increased blood creatine phosphokinase (7%), and fatigue (4%). Serious AEs were reported in 40% (71/179) of patients receiving atezolizumab plus cobimetinib including two treatment-related deaths (sepsis), 17% (15/90) of patients receiving atezolizumab, and 23% (18/80) of patients receiving regorafenib including one treatment-related death (intestinal perforation).
- Eng C. et al. Lancet Oncol.2019 Apr 16. pii: S1470-2045(19)30027-0. doi: 10.1016/S1470-2045(19)30027-0.
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This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
© Copyright 2019 MediPaper Medical Communications Ltd. – Atezolizumab with or without cobimetinib vs regorafenib for previously treated metastatic colorectal cancer (IMblaze370)