TY - JOUR
T1 - Phase i open-label study of afatinib plus vinorelbine in patients with solid tumours overexpressing EGFR and/or HER2
AU - Bahleda, Rastislav
AU - Varga, Andrea
AU - Bergé, Yann
AU - Soria, Jean Charles
AU - Schnell, David
AU - Tschoepe, Inga
AU - Uttenreuther-Fischer, Martina
AU - Delord, Jean Pierre
PY - 2018/2/6
Y1 - 2018/2/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041686298&partnerID=8YFLogxK
U2 - 10.1038/bjc.2017.436
DO - 10.1038/bjc.2017.436
M3 - Article
C2 - 29337963
AN - SCOPUS:85041686298
SN - 0007-0920
VL - 118
SP - 344
EP - 352
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -