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
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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