Phase II study evaluating the association of gemcitabine, trastuzumab, and erlotinib as first-line treatment in patients with metastatic pancreatic adenocarcinoma (GATE 1).

Abstract

379 Background: This study aimed to assess the efficacy and tolerance of the combinationof chemotherapy and two targeted therapies as a first-line treatment in metastatic pancreatic cancer patients. Methods: We designed a phase 2 open-label, non-comparative, multicenter study (NCT01204372). Patients received weekly 1000 mg/m² gemcitabine (3 weeks out of 4), weekly trastuzumab (4 mg/kg the first week, 2 mg/kg afterwards) and erlotinib 100 mg/day per os. The primary endpoint was the disease control rate (DCR) according to RECIST. Using a Fleming’s single-stage procedure, the trial was considered positive if 29 patients had a controlled disease (out of 57 evaluable patients). Secondary endpoints included the safety, the progression-free survival (PFS) and the overall survival (OS). An ancillary study addressed the EGFR, HER2 and KRAS status of the patients. Results: Between June 2010 and July 2013, 62 patients were recruited (37 men). The median age was 62 years (range 35-77). Performance status was 0 (n=27) and 1 (n=35). 10 patients had had a surgery of the primary tumor (PT), of whom 6 had been treated with a gemcitabine-based adjuvant chemotherapy (> 6-month delay). PT were localized in the head (n=25), corpus (n=22) and tail (n=15) of pancreas. The number of metastatic sites varied from 1 (n=25) to ≥ 3 (n=15). The baseline median left ventricular ejection fraction was 65% (range 51-86%). All patients were evaluable for safety and 59 patients for efficacy. Main first cycle treatment-related toxicities included: grade 3 anorexia (27%), asthenia (13%), diarrhea (10%), anemia (6%), and thrombocytopenia (3%); grade 3-4 neutropenia (24%), and mucositis (6%); grade 2-3 cutaneous events (35%). No complete responses were observed. 11 patients had a partial response, 33 a stable disease and 15 a disease progression. Therefore, the DCR was 74.6% (95%CI: 61.6-85.0%). Definitive results for the secondary endpoints will be presented at the meeting. Conclusions: Our results showed that combining gemcitabine, trastuzumab and erlotinib is efficient in terms of DCR. A further study is necessary to investigate this promising association. Funding (Roche SAS). Clinical trial information: NCT01204372.