A propensity score–matched comparison of fruquintinib (FRU) versus FRU combined with PD-1 inhibitors for microsatellite stability (MSS) metastatic colorectal cancer: Real-world data.

person Lina He Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China info_outline Lina He, Xiaojiao Cheng, Xin Cheng, Qingli Li, Shuiping Tu

Authors person Lina He Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China info_outline Lina He, Xiaojiao Cheng, Xin Cheng, Qingli Li, Shuiping Tu Organizations Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Abstract Disclosures Research Funding No funding sources reported Background: FRU has been approved for previously treated metastatic colorectal cancer (mCRC) in China and the United States, moreover it has shown synergistic effects in combination with immunotherapy in MSS CRC through immunomodulation of the tumor microenvironment. However, comparing the efficacy of FRU monotherapy (FM) and FRU combined with PD-1 inhibitors (FP) directly was rarely reported due to baseline differences in patient characteristics. To address this, we utilized the propensity score matching (PSM) to enhance the accuracy of efficacy prediction by matching relevant baseline features between the two groups. Methods: Our real-world observational study retrospectively included MSS CRC patients who have received 3 rd line and above treatments from June 2019 to July 2022, and patients diagnosed with mCRC were eligible, and all patients received at least 2 cycles of FM or FP. As a result, 16 patients in the FM group and 51 patients in the FP group were enrolled. Utilizing stable LASSO (Least Absolute Shrinkage and Selection Operator) regression, we identified key clinical features relevant to outcomes for PSM. These included liver metastasis, lung metastasis, and prior chemotherapy with VEGF inhibitors. Based on these selected features, we conducted a 1:2 nearest neighbor matching algorithm to align the patients from the two groups more accurately for comparative analysis and subsequent survival analysis. The primary endpoint was progression-free survival (PFS). Results: The PSM process resulted in a matched cohort comprising 16 patients from the FM group and 32 patients from the FP group, totaling 48 patients in the analysis. The baseline characteristics of the included population were shown in Table 1. With a median follow-up of 22.87 months (95% CI: 17.00-26.07months), the median PFS in the FP group (13.27 months, 95% CI: 9.97-15.03 months) exhibited a noticeable extension compared to the FM group (4.30 months, 95% CI: 2.83-13.60 months). Additionally, the median overall survival (OS) in the FM group was 16.93 months (95% CI: 11.70-NA), and in the FP group, it was 21.30 months (95% CI: 13.67-NA). Conclusions: The FP group showed a significant increase in PFS compared to FM and PSM increased the comparability of real-world efficacy in MSS mCRC patients receiving FRU and FRU combined with PD-1 inhibitors. Further increasing the sample size may yield more valuable results. Baseline characteristics of the population before and after PSM. FM(N = 16) n(%) FP Before PSM (N = 51) n(%) After PSM (N = 32) n(%) Age (mean ± SD)(year) 63.94 ± 9.76 60.92 ± 11.18 59.47 ± 10.24 Gender Male 9(56.2) 25(49.0) 18(56.3) Female 7(43.8) 26(51.0) 14(43.8) Liver metastasis 9(56.2) 35(68.6) 19(59.4) Lung metastasis 12(75.0) 31(60.8) 26(81.3) prior with VEGF inhibitors 10(62.5) 40(78.4) 20(62.5)