Key Clinical Takeaways:

• Capecitabine plus carboplatin demonstrated a favorable efficacy–toxicity balance as first-line therapy for metastatic or unresectable HER2-negative esophagogastric adenocarcinoma, with progression-free survival comparable to oxaliplatin-based and nanoliposomal irinotecan–based regimens but significantly lower rates of grade ≥2 neurotoxicity than capecitabine plus oxaliplatin.

• Neurotoxicity outcomes clearly differentiated platinum backbones, with capecitabine plus oxaliplatin associated with substantially higher neurotoxicity compared with both capecitabine plus carboplatin and nanoliposomal irinotecan, leucovorin, and fluorouracil, supporting carboplatin as a more tolerable alternative in this setting.
• Practical considerations favor capecitabine plus carboplatin as a first-line backbone, given its oral component, lack of central line requirement, off-patent drug availability, and preserved efficacy with or without nivolumab in patients with a Combined Positive Score ≥5.

According to results from a multicenter phase 2 trial, first-line capecitabine plus carboplatin improved outcomes among previously untreated patients with metastatic or unresectable HER2-negative esophagogastric adenocarcinoma.

These findings were presented by Dana Kamp, MD, University Medical Center Utrecht, The Netherlands, at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

In this open-label trial, 320 patients were randomized 2:2:1 to receive nanoliposomal irinotecan, leucovorin, and fluorouracil (n = 83), capecitabine plus carboplatin (n = 150), or capecitabine plus oxaliplatin (n = 80). Following the approval of nivolumab, patients with a Combined Positive Score of ≥ 5 were randomized 2:1 to receive capecitabine plus carboplatin (n = 74) or capecitabine plus oxaliplatin (n = 36) in combination with nivolumab. Primary end points included neurotoxicity and progression-free survival (PFS).

At time of analysis, grade 2/4 neurotoxicity was reported in 0 patients in the nanoliposomal irinotecan, leucovorin, and fluorouracil arm, 4 patients in the capecitabine plus carboplatin with or without nivolumab arm, and 37 patients in the capecitabine plus oxaliplatin with or without nivolumab arm. There was no significant difference in neurotoxicity between the capecitabine plus carboplatin and nanoliposomal irinotecan, leucovorin, and fluorouracil arms (P = .301); however, significant differences were observed between capecitabine plus carboplatin and capecitabine plus oxaliplatin and between nanoliposomal irinotecan, leucovorin, and fluorouracil and capecitabine plus oxaliplatin (both P < .001).

Median PFS was found to be 4.5 months, 5.8 months, and 6.4 months, respectively. Among patients treated without nivolumab, no significant difference in PFS was observed between nanoliposomal irinotecan, leucovorin, and fluorouracil and capecitabine plus carboplatin (hazard ratio [HR], 1.17; 90% confidence interval [CI], 0.890 to 1.534; P = .169) or capecitabine plus oxaliplatin (HR, 0.89; 90% CI, 0.636 to 1.258; P = .296). No significant difference in PFS was observed between capecitabine plus carboplatin and capecitabine plus oxaliplatin with or without nivolumab (HR, 0.89; 90% CI, 0.932 to 1.540; P = .118).

“Given its ease of use—no central line required—and its relatively low cost (all drugs off patent), [capecitabine plus carboplatin] can be considered the most favorable first-line chemotherapy backbone,” concluded Dr Kamp et al.

Source: 

Kamp D, Van Velzen M, Kessels R, et al. Liposomal irinotecan, carboplatin or oxaliplatin (LyRICX) with or without nivolumab in the first-line treatment of metastatic or irresectable esophagogastric adenocarcinoma: A randomized phase 2 study. Presented at ASCO Gastrointestinal Cancers Symposium. January 8 - 12, 2026; San Francisco, California. LBA287.