A retrospective analysis of taxane-based chemotherapy in small bowel adenocarcinoma

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BACKGROUND: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date. METHODS: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994 to 2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and ileum (16%). Metastatic sites included peritoneum (39%) and liver (31%). Common mutations were TP53 (63%), KRAS (47%), SMAD4 (24%), and APC (15%). Taxanes were administered as single agents (29%) or in combination (71%), most often in second- (40%) or third-line (33%) settings. Overall response rate was 24%. Median time to progression (mTTP) was 3.1 months (95% CI: 2.0-4.2) and median overall survival (mOS) was 8.7 months (95% CI: 7.4-10.1). Efficacy did not differ by treatment line, regimen type, or tumor site, but was significantly associated with TP53 status; response rate was 20% in TP53-mutated vs 45% in wild-type (P = .009), with mTTP 2.5 vs 4.9 months (P = .009) and mOS 7.3 vs 10.6 months (P = .002). On multivariable analysis, TP53 mutation predicted worse outcomes. CONCLUSION: Taxane-based therapy demonstrated activity in metastatic SBA, with 24% response and 3.1-month mTTP. TP53 mutation may be a negative predictive marker for taxane efficacy. These findings support prospective investigation in metastatic SBA.

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