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

Y Guo, M-J Ahn, A Chan, C-H Wang, J-H Kang, S-B Kim, M Bello, R S Arora, Q Zhang, X He, P Li, A Dechaphunkul, V Kumar, K Kamble, W Li, A Kandil, E E W Cohen, Y Geng, E Zografos, P Z Tang, Y Guo, M-J Ahn, A Chan, C-H Wang, J-H Kang, S-B Kim, M Bello, R S Arora, Q Zhang, X He, P Li, A Dechaphunkul, V Kumar, K Kamble, W Li, A Kandil, E E W Cohen, Y Geng, E Zografos, P Z Tang

Abstract

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 Eastern Cooperative Oncology Group (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 end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.

Results: A total of 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.

Clinical trial registration: ClinicalTrials.gov identifier: NCT01856478.

Keywords: Asian; HNSCC; afatinib; methotrexate.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.
Figure 1.
Survival outcomes. (A) Kaplan–Meier estimates of progression-free survival assessed by independent review. (B) Pre-specified subgroup analysis of progression-free survival (independent review). CI, confidence interval; CR, complete response; ECOG PS, Eastern Cooperative Group Performance Status; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; PD, progressive disease; PFS, progression-free survival; PR, partial response; R/M, recurrent or metastatic; SD, stable disease. *Cisplatin alone, cisplatin+carboplatin, nedaplatin alone and other.
Figure 2.
Figure 2.
Disease control and tumour shrinkage. (A) Objective response rate and disease control rate with afatinib and methotrexate, assessed by independent review. (B) Prespecified subgroup analyses of objective response rate (independent review). (C) Maximum percentage tumour shrinkage in individual patients. (D) Duration of response for individual patients. CI, confidence interval; CR, complete response; ECOG PS, Eastern Cooperative Group Performance Status; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; PD, progressive disease; PR, partial response; R/M, recurrent or metastatic; SD, stable disease. *Cisplatin alone, cisplatin+carboplatin, nedaplatin alone and other.
Figure 2.
Figure 2.
Disease control and tumour shrinkage. (A) Objective response rate and disease control rate with afatinib and methotrexate, assessed by independent review. (B) Prespecified subgroup analyses of objective response rate (independent review). (C) Maximum percentage tumour shrinkage in individual patients. (D) Duration of response for individual patients. CI, confidence interval; CR, complete response; ECOG PS, Eastern Cooperative Group Performance Status; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; PD, progressive disease; PR, partial response; R/M, recurrent or metastatic; SD, stable disease. *Cisplatin alone, cisplatin+carboplatin, nedaplatin alone and other.

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Source: PubMed

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