Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (PRODIGE 62-FFCD 1701-OESIRI).

BACKGROUND: Metastatic esophageal squamous cell carcinoma (mESCC) patients with disease progression after platinum-based first-line chemotherapy (CT) +/- immune checkpoint inhibitors (ICI) may benefit from second-line CT, mostly based on paclitaxel and irinotecan, but no randomized trial has compared these regimens. PATIENTS AND METHODS: PRODIGE 62-OESIRI is a multicenter, open-label, randomized phase II trial evaluating the efficacy and safety of nanoliposomal irinotecan (Nal-IRI) plus 5FU versus paclitaxel as second-line CT in mESCC. The primary endpoint was to achieve overall survival (OS) of 60 % at 9 months. RESULTS: Between March 2019 and July 2023, 106 pts were randomized. Median age was 65.6 years, 83.0 % men and 29.2 %/58.5 %/12.3 % of ECOG PS 0/1/2, respectively. As prior treatment, 48.6 % had chemoradiation, 41.9 % CT alone and 9.5 % CT plus ICI. OS at 9 months was 34.0 % [90 %CI: 22.9-46.5] and 39.2 % [90 %CI: 27.7-51.7] in the 5FU Nal-IRI and paclitaxel arms, respectively. The primary endpoint was not met. Median progression-free survival was 2.4 [95 %CI: 2.1-3.6] and 2.1 [95 %CI: 1.9-3.3] months, and median OS 7.1 [95 %CI: 5.2-8.3] and 6.6 [95 %CI: 4.8-10.3] months, respectively. Overall, 51.0 % and 38.5 % of patients experienced at least one grade 3-4 treatment-related adverse events (neuropathy: 2.0 vs. 7.7 %, diarrhea: 16.3 % vs. 0 % and vomiting: 10.2 vs. 0 %), in the 5FU Nal-IRI and paclitaxel arms, respectively. Treatment was discontinued for toxicity in 10.4 % versus 3.9 % in the 5FU Nal-IRI and paclitaxel arm, respectively. CONCLUSIONS: PRODIGE 62-OESIRI trial showed low efficacy of paclitaxel and 5FU Nal-IRI in the 2nd line treatment of mESCC, though paclitaxel provided a better safety profile. Trial registration NCT03719924.