Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)-either antiangiogenic (AA) or anti-EGFR-compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status.
Patients and methods: This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups.
Results: A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29-0.49; p < 0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28-0.51; p < 0.0001). ORR did not differ significantly (33.8% vs 43.2%; p = 0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups.
Conclusion: Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials.
Keywords: Chemotherapy; Metastasis; Small bowel adenocarcinoma; Targeted therapies.
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