1447P - Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study

Background

Metastatic esophageal squamous cell carcinoma (mESCC) patients with disease progression after platinum-based first-line chemotherapy (CT) +/- radiation +/- immune checkpoint inhibitors (ICI) may benefit from a second-line CT mostly based on paclitaxel and irinotecan but no randomized trial compared these regimens.

Methods

OESIRI-PRODIGE 62 is a multicenter, open-label, randomized phase II trial evaluating efficacy and safety of nanoliposomal irinotecan (Nal-IRI) + 5FU versus paclitaxel as second-line CT in mESCC. The primary endpoint was percentage of pts alive at 9 months (OS) (H0=40% and H1=60%). With α 5%, power 85% and 5% of pts lost to follow-up, 53 pts per arm (n=106) were required. Secondary endpoints were progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL).

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% ECOG PS 0/1/2. Most pts had lymph node (68.3%), lung (52.9%) and liver metastases (24.8%). As prior treatment, 48.6% had chemoradiation, 41.9% CT alone and 9.5% CT plus ICI. The OS rate at 9 months was 34.0% [90%CI: 22.9-46.5] and 39.2% [90%CI: 27.7-51.7] in 5FU Nal-IRI and paclitaxel arms, respectively. Primary endpoint was not met. Median PFS were 2.4 [95%CI: 2.1-3.6] and 2.1 [95%CI: 1.9-3.3] months, disease control rates 47.8% and 40.4%, and median OS 7.1 [95%CI: 5.2-8.3] and 6.6 [95%CI: 4.8-10.3] months, respectively. 51.0% and 38.5% of pts experienced at least one grade 3-4 adverse events related to the treatment (neuropathy: 2.0 vs 7.7%, leucopenia: 6.1 vs 15.4%, diarrhea: 16.3% vs 0% and vomiting: 10.2 vs 0%), in 5FU Nal-IRI and paclitaxel arms, respectively. Two toxic deaths were observed in 5FU Nal-IRI arm. Treatment stop and dose reduction for toxicity were observed in 10.4% versus 3.9%, and 77.8% versus 83.3% in 5FU Nal-IRI and paclitaxel arms, respectively. 63.0% and 48.3% had a deterioration in QoL (loss of more than 5 points of the EORTC-QLQC30).

Conclusions

OESIRI-PRODIGE 62 trial showed low efficacy of paclitaxel and 5FU Nal-IRI in 2nd line treatment for mESCC patients, though paclitaxel provided better safety profile.

Clinical trial identification

NCT03719924.

Editorial acknowledgement

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

Servier.

Disclosure

D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. C. Poisson Ligeza: Financial Interests, Personal, Invited Speaker: Servier. V. Bourgeois: Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Non financial benefits, Congress Invitation: Merck, Amgen, Viatris, Pierre Fabre, MSD. V. Jestin: Financial Interests, Personal, Other, invitation à une formation: Novartis, MSD, Merck; Financial Interests, Personal, Other, contribution organisation réunion scientifique: Leopharma; Financial Interests, Personal, Invited Speaker: Sanofi. O. Dubreuil: Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Sanofi, Pierre Fabre, Servier, MSD, AstraZeneca. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera, Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. A. Lievre: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, BMS, Esteve, Pierre Fabre Oncologie, Servier, Viatris; Financial Interests, Personal, Advisory Board: Astellas, BMS, Bayer, Servier; Financial Interests, Institutional, Research Grant, RePERSO trial: Bayer; Financial Interests, Institutional, Coordinating PI, SOCRATE trial (FFCD promotion): Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Bayer, Incyte, Lilly; Non-Financial Interests, Other, Travel and meeting registration: Bayer, Pierre Fabre, Servier, Viatris. F. Di Fiore: Financial Interests, Personal, Advisory Board: Amgen, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca, Sanofi, Bayer, Ipsen, Merck, Roche, Servier, MSD, Pierre Fabre, Takeda, Janssen. T. Lecomte: Financial Interests, Personal, Advisory Board: Sanofi, Merck Serono, Servier, Amgen, Ipsen, Pierre Fabre, AstraZeneca, Deciphera, Bayer. C. Lepage: Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Invited Speaker: Amgen, Pierre Fabre, Ipsen. V. Hautefeuille: Financial Interests, Personal, Invited Speaker: Novartis, Merck, Amgen; Financial Interests, Personal, Advisory Board: AAA, Ipsen, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Deciphera, Esteve. All other authors have declared no conflicts of interest.