1. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
- Author
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Cohen, EEW, Licitra, LF, Burtness, B, Fayette, J, Gauler, T, Clement, PM, Grau, JJ, del Campo, JM, Mailliez, A, Haddad, RI, Vermorken, JB, Tahara, M, Guigay, J, Geoffrois, L, Merlano, MC, Dupuis, N, Krämer, N, Cong, XJ, Gibson, N, Solca, F, Ehrnrooth, E, and Machiels, J-PH
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Dental/Oral and Craniofacial Disease ,Rare Diseases ,Cancer ,Clinical Research ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Administration ,Intravenous ,Administration ,Oral ,Afatinib ,Antimetabolites ,Antineoplastic ,Biomarkers ,Tumor ,Biopsy ,Carcinoma ,Squamous Cell ,Disease-Free Survival ,Head and Neck Neoplasms ,Humans ,Methotrexate ,Neoplasm Metastasis ,Neoplasm Recurrence ,Local ,Predictive Value of Tests ,Quinazolines ,Squamous Cell Carcinoma of Head and Neck ,afatinib ,methotrexate ,HNSCC ,biomarker ,phase III ,EGFR ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
BackgroundIn 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.Patients and methodsRandomized 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.ResultsOf 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 and EGFR-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).ConclusionsSubgroups 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.Clinical trial registrationNCT01345682.
- Published
- 2017