Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
Autor: | Barbara Burtness, Ezra E.W. Cohen, Jérôme Fayette, Makoto Tahara, Jean-Pascal Machiels, Robert I. Haddad, Flavio Solca, Joël Guigay, Thomas Gauler, Nicholas F. Dupuis, Marco Merlano, X.J. Cong, Audrey Mailliez, Nicole C. Krämer, Lionnel Geoffrois, Juan J. Grau, E. Ehrnrooth, Lisa Licitra, Neil W. Gibson, Paul Clement, J. M. Del Campo, Jan B. Vermorken |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oncology Antimetabolites Afatinib Biopsy Medizin afatinib Administration Oral HNSCC 0302 clinical medicine Neoplasm Metastasis Tissue microarray Tumor Hematology Antineoplastic Head and Neck Tumors Local Head and Neck Neoplasms 030220 oncology & carcinogenesis Administration Carcinoma Squamous Cell Biomarker (medicine) biomarker Administration Intravenous Veristrat Intravenous medicine.drug Oral medicine.medical_specialty Antimetabolites Antineoplastic EGFR Oncology and Carcinogenesis Disease-Free Survival methotrexate 03 medical and health sciences Predictive Value of Tests Internal medicine medicine Biomarkers Tumor Humans Progression-free survival Oncology & Carcinogenesis business.industry Squamous Cell Carcinoma of Head and Neck Head and neck cancer Carcinoma Original Articles medicine.disease Head and neck squamous-cell carcinoma phase III 030104 developmental biology Neoplasm Recurrence Squamous Cell Quinazolines Methotrexate Human medicine Neoplasm Recurrence Local business Biomarkers |
Zdroj: | Annals of Oncology Annals of oncology : official journal of the European Society for Medical Oncology, vol 28, iss 10 Annals of oncology |
ISSN: | 0923-7534 |
Popis: | Background 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. Patients and methods 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. Results 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 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). Conclusions 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. Clinical trial registration NCT01345682. |
Databáze: | OpenAIRE |
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