(S)-1(Duquesne University)

Recent advances in cancer genome analysis and the practice of precision medicine have made it possible to identify fractions with rare genetic alterations. Among biliary tract cancers, EGFR‐amplified cancers are known to be rare fractions across organs and have a poor prognosis. The use of anti‐EGFR antibody for EGFR‐amplified cancers has been promising; however, the evidence is not yet clear.

In this report, we describe the case of a 48‐year‐old man diagnosed with advanced gallbladder cancer. The patient was administered gemcitabine plus cisplatin, followed by S‐1 monotherapy; however, disease progression was observed after two cycles of each regimen. Comprehensive genomic profiling test revealed EGFR‐amplification, and the patient was treated with combination therapy with the anti‐EGFR antibody necitumumab, gemcitabine, and cisplatin. After two cycles of treatment, tumor size reduced, and the treatment response was evaluated as partial response. On Day 90, after five cycles of treatment, tumor progression was confirmed. In addition, after disease progression, liquid biopsy revealed acquired pathogenic gene alterations suggesting anti‐EGFR antibody resistance.

This report supports the clinical benefit of anti‐EGFR antibodies for EGFR‐amplified biliary tract cancers and the importance of genomic analysis in personalized therapy and drug resistance research.

This study aims to compare the effectiveness and safety of the combination of raltitrexed, S‐1 (RS), and fruquintinib with the combination of RS and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).

This retrospective cohort included mCRC patients who received the RS plus fruquintinib or regorafenib as the third‐line therapy from May 2019 to April 2023. A propensity score matching (PSM) analysis was used to balance the baseline characteristics of all patients. Overall survival (OS), progression‐free survival (PFS), tumor response, and safety of the two regimens were evaluated.

Of the 153 patients enrolled, 123 patients received the RS plus bevacizumab and 30 patients received the RS plus fruquintinib. After PSM, 30 pairs were analyzed. Patients treated with RS plus fruquintinib had a longer PFS than those treated with RS plus bevacizumab before PSM (5.0 months vs. 4.3 months, p = 0.008) and after PSM (5.0 months vs. 4.4 months, p = 0.012). A longer OS was also observed in RS plus fruquintinib group before PSM and after PSM, but there was no statistic difference between two groups after PSM. Both objective response rate and disease control rate were higher in the RS plus fruquintinib cohort than those in the RS plus bevacizumab cohort before PSM, and the difference in values between the two groups reduced after PSM. The adverse effects (AEs) of both groups were well tolerated.

In patients with refractory mCRC, RS plus fruquintinib demonstrated a superior OS, PFS than RS plus bevacizumab and had manageable AEs.