Results from the phase 3 COMMIT clinical trial found that for patients with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), combining chemotherapy and bevacizumab with atezolizumab can significantly extend progression-free survival (PFS) from just over 5 months with atezolizumab alone to more than 2 years with the combination.

The research will be presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, taking place January 8-10 in San Francisco.

“While immune checkpoint inhibitors have shown superiority over chemotherapy as first-line treatment for mCRC with dMMR or MSI-H status, results from the KEYNOTE-177 trial revealed that 29.4% of patients experienced disease progression, and the 12-month progression-free survival rate was only 55.3%. These findings highlight the need for strategies to improve the effectiveness of PD-1/PD-L1 monotherapy,” said lead study author Caio Max Sao Pedro Rocha Lima, MD, MS, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.

About the study

The COMMIT study evaluated whether combining chemotherapy and the PD-L1 immune checkpoint inhibitor atezolizumab for the initial treatment of dMMR/MSI-H mCRC could lead to better outcomes than atezolizumab alone.

From November 2017 to March 2025, the study enroled 102 patients with dMMR/MSI-H mCRC who had not yet received treatment. The median age of the participants was 62, and nearly half (48%) were female.

The patients were randomly assigned to 1 of 3 treatment groups: 

1. 41 patients received mFOLFOX6, which is a combination of common chemotherapy drugs, the targeted therapy drug bevacizumab, and atezolizumab.
2. 41 patients received atezolizumab alone.
3. 20 patients received chemotherapy with bevacizumab. However, this treatment arm was closed in June 2020 after results from the phase 3 KEYNOTE-177 clinical trial found that first-line immunotherapy led to significantly better outcomes than chemotherapy for these patients.

Key findings

For this analysis, researchers compared data from the first two treatment groups. At a median follow-up of 3.5 years, they found that:

Combining chemotherapy and bevacizumab with atezolizumab helped stop cancer growth or spread for significantly longer than atezolizumab alone.

For patients who received the combination treatment, the median PFS, or length of time until the cancer grows or spreads, was 24.5 months vs. just over 5 months for patients who received atezolizumab alone.

The overall response rate (ORR), or percentage of patients who saw their cancer shrink in response to treatment, was also higher in the combination group.

These patients had an ORR of 86.1% vs. 46% for patients who received atezolizumab alone.

The disease control rate (DCR), or percentage of patients who saw their cancer either shrink or remain stable in response to treatment, was also higher 1 year after treatment in the combination group.

The DCR in this group was 64.7% vs. 32.4% in the atezolizumab-alone group.

The combination treatment led to more side effects.

Of the patients in this group, 34 experienced a grade 3 or higher adverse event compared to 18 in the atezolizumab-alone group.

A higher number of patients in the combination group also experienced grade 5 adverse events, with 4 patients having a grade 5 adverse event compared to only 1 patient in the atezolizumab-alone group.

ASCO perspective quote

“The combination of chemotherapy, the immune checkpoint inhibitor atezolizumab, and the targeted therapy bevacizumab could be a game changer for the first-line treatment of deficient mismatch repair or microsatellite instability-high metastatic colorectal cancer. The encouraging overall response rates, disease control rates, and median progression-free survival of this combination as compared to atezolizumab alone in this trial establishes this combination as a potential new treatment option for these patients,” said ASCO Expert Vishwanath Sathyanarayanan, MD, Lead Oncosciences, Karnataka Region, Senior Consultant and Academic Advisor, Apollo Hospitals, Bangalore, India.

Next steps

The researchers plan to perform correlative biomarker analyses to identify the patient subgroups that are most likely to benefit from the combination of chemotherapy, bevacizumab, and atezolizumab.

These studies will evaluate tumour and immune microenvironment features, circulating biomarkers, and molecular correlates of response and resistance.

The goal is to improve patient selection and inform the design of future prospective trials.

Source: ASCO