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Clinical Trial
. 2025 Oct 1:228:115741.
doi: 10.1016/j.ejca.2025.115741. Epub 2025 Aug 22.

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

David Tougeron  1 , Laurent Mineur  2 , Aziz Zaanan  3 , Melissa Kadi  4 , Catherine Poisson Ligeza  5 , Vincent Bourgeois  6 , Jérôme Martin-Babau  7 , Aurélie Fadin  8 , Véronique Jestin le Tallec  9 , Valérie Ly Lebrun  10 , Olivier Dubreuil  11 , Faiza Khemissa Akouz  12 , Elsa Thimonier  13 , Olivier Bouché  14 , Astrid Lièvre  15 , Frédéric Di Fiore  16 , Thierry Lecomte  17 , Côme Lepage  4 , Vincent Hautefeuille  18 ; PRODIGE 62-FFCD 1701-OESIRI investigators/collaborators
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Free article
Clinical Trial

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

David Tougeron et al. Eur J Cancer. .
Free article

Abstract

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.

Keywords: Esophageal cancer; Irinotecan; Paclitaxel; Squamous cell carcinoma.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DT reports receiving consulting or advisory board fees from Astra Zeneca, Sanofi, Amgen, MSD, BMS, Roche, Servier, Pierre Fabre, Merck, Astellas, Takeda; receiving research funding from Pierre Fabre and Sandoz. LM reports receiving consulting or advisory board fees from BMS, GSK travel and congress registration from Merck, Amgen, and research funding from Sanofi and Biocon. AZ reports receiving consulting or advisory board fees from Amgen, Astellas, Merck, Roche, Sanofi, Servier, Baxter, MSD, BMS, Pierre Fabre, Havas Life, Alira Health, Zymeworks, Daiichi Sankyo and Astra Zeneca. VB reports receiving consulting or advisory board fees from Pierre Fabre, Servier, receiving research funding from Servier and Astra Zeneca. VJLE reports receiving consulting or advisory board fees from Amgen, Novartis, Merck, Pierre Fabre, Accord, Astra Zeneca and MSD. OD reports receiving consulting or advisory board fees from Deciphera, Merck-Serono, Sanofi, Servier, Novartis, MSD, BMS, Pierre Fabre, and Astra Zeneca. FKA reports receiving consulting or advisory board fees from, Roche, Sanofi, Servier, Fresenius Kabi, MSD, and Astra Zeneca. OB reports receiving consulting or advisory board fees from Amgen, Astellas, BMS, Deciphera, Merck, Pierre Fabre, Servier, Takeda, and MSD. AL reports honoraria for lectures from Amgen, Astellas, Astra-Zeneca, BMS, Esteve, MSD, Pierre Fabre, Servier and Viatris; honoraria for consulting/advisory relationship from Astellas, Bayer, BMS, Servier and Takeda; received travel (or congress registration) support from Bayer, Esteve, Ipsen, Pierre Fabre, Servier, Viatris; received research funding from Bayer, Lilly, FDF reports receiving consulting or advisory board fees from Amgen, Astra Zeneca, Bayer, BMS, Janssen, Incyte, Merck, MSD, Novartis, Pierre Fabre, Roche, Sandoz, Sanofi, Servier, Takeda, and Viatris. TL reports receiving consulting or advisory board fees from Servier, Pierre Fabre, Merck Serono, BMS, MSD, Astra Zeneca, AAA, Sanofi and research funding from Pierre Fabre and Leo Pharma. CL reports receiving consulting or advisory board fees from Amgen, Novartis, Pierre Fabre, Ipsen, Abbvie, Deciphera. VH reports honoraria for consulting or advisory board for AdAcAp/Novartis, Deciphera, Esteve, Ipsen, Merck, MSD, Pierre Fabre, Servier All remaining authors have declared no conflicts of interest.

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