Atezolizumab, Cobimetinib Combination Failed to Improve Survival Versus Regorafenib in Relapsed Colorectal Cancer

The combination of atezolizumab plus cobimetinib did not improve progression-free survival (PFS) or overall survival (OS) compared with regorafenib in patients with previously treated unresectable locally advanced or metastatic microsatellite-stable colorectal cancer (CRC), according to phase 3 data presented at the ESMO World Congress on Gastrointestinal Cancer 2018.¹

Cobimetinib inhibits MEK1/2, which are components of the MAPK pathway. Downregulation of this pathway may alter the tumor microenvironment and improve T-cell response against tumor cells. The investigators hypothesized that the addition of cobimetinib to atezolizumab would further improve immune recognition and result in better antitumor activity.

The international, open-label, phase 3 IMblaze370 trial (ClinicalTrials.gov Identifier: NCT02788279) randomly assigned 363 patients with unresectable locally advanced or metastatic CRC that was microsatellite stable or microsatellite instability-low to receive 2:1:1 atezolizumab plus cobimetinib, atezolizumab alone, or regorafenib. The primary endpoint was OS and the secondary endpoints included PFS, objective response rate (ORR), and duration of response.

At enrollment, the median age was 58 and 26% of patients had received more than 3 prior therapies. A RAS mutation was present in 54.3% of tumors.

There was no difference in ORR, PFS, OS between groups. The ORR was 2.7% with atezolizumab plus cobimetinib compared with 2.2% each with atezolizumab monotherapy or regorafenib. The median OS was 8.9 with atezolizumab plus cobimetinib (hazard ratio [HR], 1.00; 95% CI, 0.73-1.38) and 7.1 months with atezolizumab alone (HR, 1.19; 95% CI, 0.83-1.71) compared with 8.5 months with regorafenib. The median PFS was also similar with atezolizumab plus cobimetinib (HR, 1.25; 95% CI, 0.94-1.65) and atezolizumab monotherapy (HR, 1.39; 95% CI, 1.0-1.94) compared with regorafenib.

Grade 3/4 treatment-related adverse events (TRAEs) occurred more frequently among patients who received regorafenib at 49% compared with 45% of patients treated with atezolizumab plus cobimetinib and 10% of patients who received atezolizumab monotherapy. TRAEs that occurred in more than 30% of patients who received the combination included diarrhea, rash, and nausea, whereas palmar-plantar erythrodysesthesia, fatigue, diarrhea, and decreased appetite occurred with regorafenib. There were no grade 3/4 TRAEs that occurred in more than 30% of patients in the atezolizumab monotherapy group.

The authors stated that in the IMblaze370 trial, atezolizumab plus cobimetinib or atezolizumab monotherapy did not meet the primary endpoint.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO World Congress on Gastrointestinal Cancer 2018 meeting by visiting the conference page.

Reference

1. Bendell J, Ciardiello F, Tabernero J, et al. Efficacy and safety results from IMblaze370, a randomised phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer. Ann Oncol. 2018;29 (suppl 5;abstr LBA-004):v123. doi: 10.1093/annonc/mdy208.003