Abstract 484: Immune checkpoint inhibitor therapy for metastatic colorectal cancer: Real-world practice patterns and predictors of overall survival
Authors: Bari Shahla , Matejcic Marco , Kim Richard , Xie Hao , Carballido Estrella , Sahin Ibrahim , Powers Benjamin , Felder Seth , Schmit Stephanie 
Published: July 2021

There is well-established evidence of a therapeutic role for immune checkpoint inhibitors (ICIs) in mismatch repair deficient (MMR-D) metastatic colorectal cancer (mCRC). However, factors associated with receipt and response to ICIs in the real-world setting are not well-characterized. Using electronic health record-derived, de-identified data from the nationwide Flatiron Health database, we selected 568 patients diagnosed with mCRC between January 2013 and December 2019 who received at least one line of ICI therapy in their treatment course (median age: 62.9 years, 50.2% male, 69.4% White, 44% stage IV at diagnosis, 41.2% MMR-D). Overall survival (OS) was defined as the time period from start of ICI therapy until death or last patient activity. Differences in sociodemographic (e.g. age, sex), clinical (e.g. stage at diagnosis, anatomic site) and molecular (e.g. MMR status) characteristics between patients who did and did not receive ICI therapy were compared using chi-square or t-tests. Univariate and multivariate Cox regression models were used to identify predictive factors associated with OS among patients treated with ICIs. Median OS from start of ICI therapy was 8.95 months, while the 1-year probability of survival was 42.6%. Compared to patients who did not receive ICI therapy (n=18,366), patients who received ICIs were initially diagnosed at earlier stage (I-III), were more likely to have MMR-D tumors (p&lt;0.001), and were more likely to have colon cancer (p&lt;0.001). Among patients who received ICIs, MMR-D status (vs. mismatch repair proficient [MMR-P]; HR=0.33, 95%CI=0.22-0.51, p=1x10-6), albumin level ≥3 g/dL (vs. &lt;3 g/dL; HR=0.34, 95%CI=0.21-0.53, p=2x10-6) and concurrent antibiotic intake (yes vs. no; HR=0.51, 95%CI=0.34-0.75, p=8x10-4) were statistically significantly associated with higher OS, while stage IV disease at diagnosis (vs. stage I-III; HR=1.80, 95%CI=1.22-2.66, p=0.003) was significantly associated with lower OS. Patients with MMR-P tumors who received an early line of ICI therapy (1 or 2) or a combination therapy (e.g. ICIs + chemotherapy) had significantly higher OS than patients who received ICIs at a later line (&gt;2) or ICIs alone (p=0.0074 and 0.0057, respectively). In the multivariable model, high albumin level (HR=0.27, 95%CI=0.16-0.45, p=5x10-7) and antibiotic intake (HR=0.46, 95%CI=0.29-0.74, p=0.001) remained statistically significantly associated with higher OS among patients with MMR-P tumors. Our findings support that MMR status is a key predictor for OS in mCRC patients treated with ICI therapy and provide insights into additional specific clinical features that may predict response to ICIs in a real-world setting.

Citation Format: Shahla Bari, Marco Matejcic, Richard Kim, Hao Xie, Estrella Carballido, Ibrahim Sahin, Benjamin Powers, Seth Felder, Stephanie Schmit. Immune checkpoint inhibitor therapy for metastatic colorectal cancer: Real-world practice patterns and predictors of overall survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 484.