Who Benefits Most From Immunotherapy in Metastatic CRC?

TOPLINE:

Compared with chemotherapy, immune checkpoint inhibitors (ICIs) were associated with improved overall survival in patients with microsatellite instable metastatic colorectal cancer (CRC), particularly when used as first-line therapy in routine clinical practice as well as in patients with high albumin levels and those who received antibiotics. Patients with microsatellite instable disease were also less likely to discontinue ICI therapy.

METHODOLOGY:

• The US Food and Drug Administration has approved ICIs to treat microsatellite instable metastatic CRC; however, factors influencing their use and effectiveness in real-world settings remain less clear.
• Researchers used de-identified data from a nationwide electronic health record–derived database (between January 2013 and June 2019) and analyzed 18,932 patients with metastatic CRC (median age at diagnosis, 64.6 years) who underwent treatment.
• ICI-based therapy included administration of any of the following drugs during treatment: Nivolumab, pembrolizumab, atezolizumab, ipilimumab, tremelimumab, durvalumab, or avelumab.
• Primary outcomes were receipt of ICI and overall survival; the secondary outcome was time to treatment discontinuation.
• The median follow-up duration was 16.7 months.

TAKEAWAY:

• Patients with microsatellite instable tumors were significantly more likely to receive ICIs than those with microsatellite stable tumors (odds ratio [OR], 22.66; P < .001). Those with synchronous metastatic CRC were less likely to receive ICIs than those with metachronous disease (OR, 0.57; P < .001).
• Patients with microsatellite instable tumors who received ICIs as a first-line treatment had significantly longer overall survival than those who received chemotherapy alone (hazard ratio [HR], 0.37; P < .001).
• Among patients with microsatellite stable tumors, ICI-based therapy was associated with longer overall survival in those with high (vs low) levels of albumin (HR, 0.28; P < .001) and in those with antibiotic use vs nonuse (HR, 0.43; P < .001) but significantly shorter overall survival in those with synchronous (vs metachronous) metastatic CRC (HR, 1.90; P = .003).
• Patients with microsatellite instable (vs stable) tumors demonstrated significantly lower rates of immunotherapy discontinuation (HR, 0.41) as did those with high (vs low) levels of albumin (HR, 0.54) and antibiotic use vs nonuse (HR, 0.68; all P < .05). Conversely, men (vs women) and patients with synchronous (vs metachronous) metastatic CRC were more likely to discontinue immunotherapy (HR, 1.34; P = .02 and HR, 1.65; P < .001, respectively).

IN PRACTICE:

“In this study of routine clinical practice data from US oncology practices, patients with MSI-H [microsatellite instability–high] [metastatic] CRC who received ICIs in an early line of therapy had significantly longer survival expectancy and lower likelihood of therapy discontinuation compared with those treated with chemotherapy only. Our findings provide substantial evidence to support results from the KEYNOTE-177 study toward higher efficacy of first-line pembrolizumab vs chemotherapy” in this patient population, the authors wrote.

SOURCE:

This study, led by Shahla Bari, MD, Duke Cancer Institute, Durham, North Carolina, was published online in JAMA Network Open.

LIMITATIONS:

This study was limited by incomplete or missing data on surgery, comprehensive somatic genetic/molecular features, tumor mutational burden, drug-related adverse effects, and germline testing.

DISCLOSURES:

No funding information was provided for this study. Two authors reported having ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.