A phase II open-label trial of dacomitinib monotherapy in patients with HER2-positive advanced gastric cancer after failure of at least one prior chemotherapy regimen.

Abstract

54 Background: HER2 is a clinically relevant therapeutic target in gastric cancer. Trastuzumab plus chemotherapy has improved patients’ survival in HER2 (+) advanced gastric cancer (AGC). Pan-HER inhibitor shows significant antitumor effects in in vitro and xenograft model of HER2 (+) gastric cancer. The aim of this study was to find the efficacy/safety of dacomitinib, a irreversible pan-HER tyrosine kinase inhibitor by Pfizer, in HER2 (+) AGC patients. Methods: We enrolled AGC patients with HER2 FISH (+) or HER2 IHC 3+ who were treated with at least one prior palliative chemotherapy regimen and with ECOG PS 0-2, normal cardiac ejection fraction. Patients were treated with dacomitinib 45 mg once daily continuously every 4 weeks. Response was evaluated every 8 weeks using RECIST v1.1 and safety was assessed with CTCAE v4.0. The primary endpoint was 4 month-progression free survival rate (4m-PFS). PK and PD study were also conducted. Results: A total of 27 patients were enrolled. The median age was 61 (range: 43-80). Twenty two patients were male. The ECOG PS was 0 in 9 patients, 1 in 16, and 2 in 2. The number of prior palliative chemotherapy regimen was 1 in 7 patients (25.9%), 2 in 9 (33.3%), more than 3 in 11 (40.7%). Six patients received prior anti-HER2 therapy (trastuzumab 2, lapatinib 2, lapatinib or placebo in clinical trial 2) A total of 80 cycles were delivered (median 2 cycles per patient, range: 1-6). The 4m-PFS was 22.2 % and median progression-free survival was 2.1 months (95% CI: 2.3-3.4) There was 2 PR, 9 SD and 16 PD, resulting in 7.4 % response rate (95% CI: 0-17.5%) and 40.7 % disease control rate (95% CI: 21.9-59.6%). Median overall survival was 7.1 months (95% CI: 4.4-9.8). The most common toxicities were skin rash, diarrhea, and fatigue, but most of them were grade ½. Grade 3 skin rash was observed in 3 patients. There was no treatment-related death. Conclusions: Considering the heavily pretreated nature of enrolled patients, the dacomitinib is active and safe treatment option in HER2 (+) AGC patients. The results of PK and PD studies will be also presented at the meeting. (ClinicalTrials.gov: NCT01152853 )