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Phase II study evaluating the association of gemcitabine, trastuzumab and erlotinib as first‐line treatment in patients with metastatic pancreatic adenocarcinoma ( GATE 1)
Author(s) -
Assenat Eric,
Mineur Laurent,
Mollevi Caroline,
LopezCrapez Evelyne,
LombardBohas Catherine,
Samalin Emmanuelle,
Portales Fabienne,
Walter Thomas,
Forges Hélène,
Dupuy Marie,
BoissièreMichot Florence,
HoPunCheung Alexandre,
Ychou Marc,
Mazard Thibaut
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33225
Subject(s) - medicine , gemcitabine , erlotinib , trastuzumab , clinical endpoint , gastroenterology , oncology , rash , neutropenia , phases of clinical research , response evaluation criteria in solid tumors , progressive disease , pancreatic cancer , hazard ratio , toxicity , cancer , chemotherapy , epidermal growth factor receptor , breast cancer , clinical trial , confidence interval
In a previous phase II study (THERAPY), cetuximab and trastuzumab combination, as second‐line after progression with gemcitabine, showed disease stabilization in 27% of 33 patients with pancreatic carcinoma. In the present phase II multicenter study, we assessed the efficacy and tolerance of gemcitabine, trastuzumab plus erlotinib as first‐line treatment of metastatic pancreatic cancer. The primary endpoint was disease control rate (DCR, RECIST v.1); secondary endpoints were progression‐free (PFS), overall (OS) survival and toxicity (NCI‐CTCAE v3.0). Ancillary study addressed the predictive value of both EGFR/HER2 expression and KRAS mutational status. Sixty‐three patients from four centers were included (62 evaluable for toxicity, 59 for efficacy), median age was 62 years (35‐77), 59.7% men. The median treatment duration was 16.1 weeks (2.1‐61). Eleven patients (19%) reported a partial tumor response, and 33 (56%) disease stabilization. DCR was 74.6% (95%CI: 61.8‐85.0; 44/59 patients). After a median follow‐up of 23.3 months (0.6‐23.6), median PFS was 3.5 months (95%CI: 2.4‐3.8) and median OS 7.9 months (95%CI: 5.1‐10.2). PFS was significantly longer in patients with grade ≥ 2 cutaneous toxicities vs patients with grade 0‐1 toxicities (HR = 0.55, 95%CI: 0.33‐0.92, P = .020). Expression of EGFR and HER2 was correlated with PFS and OS in multivariate analysis; HER2 expression was correlated with the tumor response. Main severe toxicities were neutropenia (32%), cutaneous rash (37%) and thrombosis/embolisms (35.5%). This triplet combination is effective in terms of disease control, PFS and OS, and acceptable for safety. A larger study to investigate this combination compared to the standard regimen should be discussed.