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Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer.
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 Oct 01; Vol. 28 (10), pp. 2526-2532. - Publication Year :
- 2017
-
Abstract
- 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.<br />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.<br />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).<br />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.<br />Clinical Trial Registration: NCT01345682.<br /> (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)
- Subjects :
- Administration, Intravenous
Administration, Oral
Afatinib
Antimetabolites, Antineoplastic administration & dosage
Biomarkers, Tumor blood
Biopsy
Carcinoma, Squamous Cell blood
Carcinoma, Squamous Cell pathology
Disease-Free Survival
Head and Neck Neoplasms blood
Head and Neck Neoplasms pathology
Humans
Neoplasm Metastasis
Neoplasm Recurrence, Local blood
Neoplasm Recurrence, Local pathology
Predictive Value of Tests
Squamous Cell Carcinoma of Head and Neck
Biomarkers, Tumor metabolism
Carcinoma, Squamous Cell drug therapy
Carcinoma, Squamous Cell metabolism
Head and Neck Neoplasms drug therapy
Head and Neck Neoplasms metabolism
Methotrexate administration & dosage
Neoplasm Recurrence, Local drug therapy
Neoplasm Recurrence, Local metabolism
Quinazolines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1569-8041
- Volume :
- 28
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 28961833
- Full Text :
- https://doi.org/10.1093/annonc/mdx344