In the Phase III LHN1 trial, second-line afatinib (A) significantly improved PFS (primary endpoint) vs methotrexate (MTX) in pts with R/M HNSCC. Tumour biomarker analyses have shown that survival benefit with A vs MTX was more pronounced in pts with p16/ErbB3-negative, EGFR-amplified, PTEN-positive disease. We present post-hoc analyses of A long-term responders (LTRs).
Pts with incurable R/M HNSCC who had received first-line platinum-based therapy were randomised to A (40mg/day) or MTX (40mg/m2/week) and treated until progression/intolerable AE. LTRs were defined as pts treated with A ≥ 12 mos. Tumour biomarkers were assessed by IHC (p16, ErbB3, PTEN, cMET) and FISH (EGFR amplification); pre-treatment (tx) serum samples were analysed with the VeriStrat® (VS) test and classified as VS-Good/Poor.
11/322 (3%) pts treated with A were LTRs with a median (range) tx-duration of 16 (12–39) mos. All pts had stopped tx at analysis. Baseline characteristics in LTRs were similar to the overall dataset, except (LTRs/overall): oral cavity primary tumour site (45%/29%); M1 disease (45%/66%); previous therapy with EGFR-antibodies (18%/59%). Median OS was 18.1 mos; median PFS (central independent review) was 14.9 mos. ORR was 45% (CR: 18%; n = 2). The frequency of pts who received ≥1 subsequent therapy was similar to the overall dataset (LTRs, 45%; overall, 51%). In LTRs with available biomarker data, 3/3 (100%) pts were p16-negative, 4/4 (100%) pts were ErbB3-negative, 2/4 (50%) pts were PTEN-positive, 3/3 (100%) pts were cMET-positive, 2/3 (67%) pts had EGFR-amplification, and 5/5 (100%) pts were VS-Good. Tolerability-guided dose reductions were more frequent among LTRs (55% vs 32% overall).
In the LHN1 study, some platinum-pre-treated pts with R/M HNSCC derived a long-term survival benefit from A; median OS was ∼1.5 yrs and >11 mos longer than in the overall dataset. Limited biomarker data available in these LTRs suggests that p16/ErbB3-negativity and EGFR-amplification might be potential predictive biomarkers for long-term benefit from A; however, results were not conclusive due to small sample size.
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J-P. Machiels: Reports taking part in advisory boards for Debio, Innate, Nanobiotix, MSD, AstraZeneca, and grants from Janssen, Bayer, and Novartis outside the submitted work. K. Okami: Honoraria: Merck Serono Co., Ltd C. Le Tourneau: Advisory board: MSD, Amgen, BMS. Honoraria: MSD, BMS, Merck Serono, Novartis. E. Zografos: Employment Boehringer Ingelheim L. de Souza Viana: Research funding from Boehringer Ingelheim. L. Licitra: Participated in advisory boards for Eisai, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Merck Serono, Amgen, Boehringer Ingelheim, Debiopharm, VentiRX, SOBI, Novartis, AstraZeneca and Bayer. E. Cohen: Participated in a consulting or advisory role for AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Merck, and Novartis, and has participated in speakers’ bureaus for Bayer and Eisai. N. Dupuis: Owns stock in Biodesix. J. Love, E. Ehrnrooth: Employee of Boehringer Ingelheim. J. Fayette: Received honoraria from Bristol-Myers Squibb and AstraZeneca. R. Galiulin, M. Tahara, K. Hoermann: COI to follow All other authors have declared no conflicts of interest.