The addition of atezolizumab to capecitabine and bevacizumab therapy is associated with marginally longer progression-free survival (PFS) compared with placebo among patients with refractory metastatic colorectal cancer (mCRC), according to study results published in JAMA Network Open.

Researchers enrolled patients for a phase 2 randomized, double-blind, placebo-controlled study, called BACCI (ClinicalTrials.gov Identifier: NCT02873195), from September 25, 2017, through June 28, 2018. Eligible study participants were aged 18 years and older, had histologically verified CRC, including histologic or clinical documentation of metastatic disease. Patients had also experienced disease progression while receiving fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and antiepidermal growth factor receptor antibody therapy. Some patients could not tolerate treatment or treatment was contraindicated.

Patients were randomly assigned 2:1 to receive capecitabine and bevacizumab plus atezolizumab (investigational group) or capecitabine and bevacizumab plus placebo (placebo group). Study participants received oral capecitabine (850 or 1000 mg/m2) twice daily on days 1 to 14, intravenous bevacizumab (7.5 mg/kg) on day 1, and either intravenous atezolizumab (1200 mg; investigational group) or placebo (placebo group) on day 1 for each 21-day cycle.


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The primary endpoint was unconfirmed investigator-assessed PFS, which researchers noted as time from randomization to first record of disease progression or any cause from mortality.

A total of 133 patients were enrolled — 128 of which were assessed for the primary endpoint. The median follow-up duration for PFS was 20.9 months. Study participants had a median age of 58.0 years (IQR, 51.0-65.0 years), 39.8% were women, and 78.9% self-identified as White.

In the primary analysis of 123 PFS events, the median PFS in the investigational group was 4.4 months (95% CI, 4.1-6.4 months) vs 3.6 months in the placebo group (95% CI, 2.2-6.2 months; hazard ratio [HR], 0.75 [95% CI, 0.52-1.09]; 1-sided log-rank P =.07), which was statistically significant.

Regarding the 12-month PFS estimate, the investigational group measured 15.2% (95% CI, 9.1%-25.6%) compared with 6.9% (95% CI, 2.3%-20.5%) in the placebo group. The HR for PFS among patients with microsatellite-stable/proficient mismatch repair tumors was 0.66 (95% CI, 0.44-0.99).

The investigational and placebo groups had a comparable median overall survival (OS) of 10.3 months (95% CI, 8.3-15.2 months) vs 10.2 months (95% CI, 8.5-16.6 months), respectively; HR, 0.96 (95% CI, 0.63-1.45); 1-sided log-rank P =.42). The 12-month survival estimates were 44.5% (95% CI, 34.7%-57.1%) and 42.0% (95% CI, 29.4%-59.9%) in the investigational and placebo groups, respectively.

Patients without liver metastasis had greater benefit of atezolizumab for PFS and OS vs those with liver metastasis (primary analysis of PFS: HR, 0.63 [95% CI, 0.27-1.47] vs 0.77 [95% CI, 0.51-1.17]; OS: HR, 0.33 [95% CI, 0.11-1.02] vs 1.14 [95% CI, 0.72-1.81]).

The researchers noted that their analysis did not include an independent or central image review, confirmatory scans, or a standardized methodologic approach for determining microsatellite instability status. In addition, long-term follow-up was limited, and the Immune Response Evaluation Criteria in Solid Tumors approach was not used.

“The addition of atezolizumab to capecitabine/bevacizumab did not provide a clinically meaningful increase in PFS among the overall population of patients with refractory mCRC,” the investigators noted.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Mettu NB, Ou F-S, Zemla TJ, et al. Assessment of capecitabine and bevacizumab with or without atezolizumab for the treatment of refractory metastatic colorectal cancer: a randomized clinical trial. JAMA Netw Open. Published online February 18, 2022. doi:10.1001/jamanetworkopen.2021.49040