Phase III study of afatinib vs methotrexate (MTX) for second-line recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients after platinum-based chemotherapy (CT) in Asia/Middle East/North Africa: LUX-Head & Neck 3 (LUX-H&N3)

Background

HNSCC patients who progress after first-line platinum-based CT for R/M disease have few treatment options. In the Phase III LUX-H&N1 trial, afatinib, an irreversible ErbB family blocker, significantly improved progression-free survival (PFS) and health-related quality of life (HRQoL) compared with MTX in this patient population (Machiels et al, Lancet Oncol 2015). The LUX-H&N3 trial, sharing a similar study design, evaluates afatinib vs MTX in the same treatment setting in patients in Asia/Middle East/North Africa.

Trial design

LUX-H&N3 is a Phase III, open-label, randomized trial evaluating efficacy and safety of afatinib vs MTX in R/M HNSCC patients progressing on/after first-line platinum-based CT (NCT01856478). Key eligibility criteria: age ≥18 years; ECOG PS 0 or 1; histologically or cytologically confirmed R/M HNSCC not amenable for salvage surgery or radiotherapy; documented progressive disease (PD) after ≥2 cycles of cisplatin/carboplatin for R/M disease (>1 systemic therapy not allowed). Prior treatment with EGFR-targeted antibody therapy but not EGFR-targeted small molecules is allowed. Patients are randomized 2:1 to afatinib (40 mg/day orally) or MTX (40 mg/m² IV weekly), stratified by ECOG PS (0/1) and prior EGFR-targeted antibody therapy in the R/M setting (Yes/No). The initial afatinib dose must be escalated to 50 mg after ≥4 weeks with minimal drug-related adverse events (AEs), or reduced by 10 mg decrements to a minimum of 20 mg in case of drug-related grade ≥3 or selected grade 1/2 AEs. The MTX dose can be escalated to 50 mg/m², or reduced by 10 mg/m² decrements to a minimum of 20 mg/m² in case of drug-related grade ≥2 or selected grade >1 AEs. Treatment will continue until PD or intolerable AEs. Treatment may continue beyond PD in case of clinical benefit as judged by the investigator. The primary endpoint is PFS; secondary endpoints include overall survival, objective response, HRQoL, and safety. Target enrollment is 300 patients; recruitment is ongoing.

Clinical trial identification

NCT01856478

Disclosure

M.-J. Ahn: involvement with an advisory board for BMS, ARIAD and Lilly.

A. Chan: advisory board involvement with Merck and Pfizer and research funding from Merck, Eli Lilly, Boehringer Ingelheim and Amgen. J.H. Kang: advisory board involvement with Boehringer Ingelheim, Eli Lilly, Pfizer and ONO Pharmaceutical Co.; corporate-sponsored research for Eli Lilly; and honoraria from Pfizer, Novartis and Boehringer Ingelheim. E. Cohen: involvement with an advisory board for Merck and Pfizer and honoraria from Eisai and Bayer. G.-Q. Hu, Y. Geng, E. Ehrnrooth: employment with Boehringer Ingelheim.

All other authors have declared no conflicts of interest.