Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer

• Published in: Annals of oncology Vol. 28; no. 10; pp. 2526 - 2532
• Main Authors: Cohen, E.E.W., Licitra, L.F., Burtness, B., Fayette, J., Gauler, T., Clement, P.M., Grau, J.J., del Campo, J.M., Mailliez, A., Haddad, R.I., Vermorken, J.B., Tahara, M., Guigay, J., Geoffrois, L., Merlano, M.C., Dupuis, N., Krämer, N., Cong, X.J., Gibson, N., Solca, F., Ehrnrooth, E., Machiels, J.-P.H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2017; Oxford University Press
• Subjects: Administration, Intravenous; Administration, Oral; Afatinib; Antimetabolites, Antineoplastic - administration & dosage; biomarker; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Biopsy; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Disease-Free Survival; EGFR; Head and Neck Neoplasms - blood; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; HNSCC; Humans; methotrexate; Methotrexate - administration & dosage; Neoplasm Metastasis; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Original; phase III; Predictive Value of Tests; Quinazolines - administration & dosage; Squamous Cell Carcinoma of Head and Neck; afatinib; methotrexate; biomarker; HNSCC; EGFR; phase III
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdx344

In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50–0.97)],EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33–0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37–0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29–1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative andEGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28–0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31–0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat ‘Good’ versus ‘Poor’ [2.7 versus 1.5 months; HR 0.71 (0.49–0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative,EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. NCT01345682.