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

Abstract 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 1994-2024. 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 = 0.009), with mTTP 2.5 vs 4.9 months (P = 0.009) and mOS 7.3 vs 10.6 months (P = 0.002). 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.