Phase i open-label study of afatinib plus vinorelbine in patients with solid tumours overexpressing EGFR and/or HER2

Rastislav Bahleda, Andrea Varga, Yann Bergé, Jean Charles Soria, David Schnell, Inga Tschoepe, Martina Uttenreuther-Fischer, Jean Pierre Delord

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    8 Citations (Scopus)

    Résumé

    Background:This phase Ib study evaluated afatinib plus vinorelbine in patients with advanced solid tumours overexpressing epidermal growth factor receptor (EGFR) and/or human EGFR 2 (HER2).Methods:Maximum tolerated doses (MTDs) were determined for afatinib (20, 40 or 50 mg, once daily) combined with standard intravenous vinorelbine (part A; 25 mg m '2 per week) or oral vinorelbine (part B; 60 mg m '2 per week, increased to 80 mg m '2 per week at week 3). Secondary end points for expanded MTD cohorts included assessments of safety, pharmacokinetics, tumour response and progression-free survival (PFS).Results:The afatinib MTD was 40 mg with intravenous (MTD A) and oral (MTD B) vinorelbine. The most frequent cycle 1 dose-limiting toxicities were febrile neutropenia and diarrhoea, consistent with individual safety profiles of vinorelbine and afatinib. Common treatment-related adverse events included: diarrhoea (92.7%), asthenia (76.4%), nausea (63.6%), neutropenia (56.4%) and vomiting (54.5%). No notable pharmacokinetic interactions were observed. Best overall tumour response was stable disease in part A (16 out of 28 patients), and partial response in part B (3 out of 27 patients). Median PFS was 14.6 and 15.9 weeks for patients treated at the MTD A and MTD B, including dose-escalation and expansion cohorts.Conclusions:Afatinib in combination with intravenous or oral vinorelbine demonstrated a manageable safety profile and antitumour activity at the MTD of 40 mg per day.

    langue originaleAnglais
    Pages (de - à)344-352
    Nombre de pages9
    journalBritish Journal of Cancer
    Volume118
    Numéro de publication3
    Les DOIs
    étatPublié - 6 févr. 2018

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