Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head&Neck 3): an open-label, randomised phase III trial
Mené sur 340 patients asiatiques atteints d'un carcinome épidermoïde de la tête et du cou de stade métastatique ou récidivant, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'afatinib et du méthotrexate en traitement de deuxième ligne, après l'échec d'un traitement à base de sels de platine (durée médiane de suivi : 6,4 mois)
Background : Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. Patients and methods : In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an ECOG performance status of 0/1. Patients were randomised (2:1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary endpoint was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. Results : 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48–0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). Conclusions : Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.