Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND

A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC.

METHODS

This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m

FINDINGS

Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%).

INTERPRETATION

The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE.

FUNDING

French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC.

TRANSLATION

For the French translation of the abstract see Supplementary Materials section.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests JG has been an advisory board member for BMS, Hookipa, MSD, Merck, Nanobiotix, and Roche, outside the submitted work; reports personal fees from MSD, outside the submitted work; and has received grant support during the study, paid to his institution, from the GEMLUC and GEFLUC, and the French National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer, through the French programme PAIR-VADS 2011. F-RF reports travel support for congress from Merck Serono, outside the submitted work. ES-B reports personal fees from MSD and Merck Serono, and support for attending meetings or travel, or both, from MSD and Merck Serono, outside the submitted work. JF reports personal fees and non-financial support from MSD and Merck, and personal fees from AstraZeneca, BMS, Roche, Rakuten, Elevar, Hookipa, Sanofi, and Seagen, during the conduct of the study; and has been an advisory board member for Roche, Seagen, and Elevar, outside the submitted work. FR reports personal fees and non-financial support from Merck, outside the submitted work. CF reports personal fees from Astellas Pharma, AstraZeneca, Biogaran, BMS, Chugai Pharma France, Clovis Oncology, Eisai, GSK, Leo Pharma, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Seagen, and Viatris, and non-financial support from AstraZeneca, Janssen Oncology, Leo Pharma, and Pierre Fabre, outside the submitted work. TC reports personal fees from Merck and has been an advisory board member for MSD outside the submitted work. PDa reports personal fees from Lilly and has been advisory board member for Pfizer and MSD, outside the submitted work. SL has participated on advisory boards of Merck and BMS, outside the submitted work. AA reports grants from the French programme PAIR-VADS 2011 funded by the French National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer, and grants from Sandoz, during the conduct of the study, and other from MSD, outside the submitted work; all paid to her institution. All other authors declare no competing interests.