A PHASE II OPEN LABEL TRIAL OF PF-00299804 MONOTHERAPY IN PATIENTS WITH HER-2 POSITIVE ADVANCED GASTRIC CANCER AFTER FAILURE OF AT LEAST ONE PRIOR CHEMOTHERAPY REGIMEN

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Abstract

Background

HER-2 is a clinically relevant therapeutic target in gastric cancer. Trastuzumab plus chemotherapy has improved patients' survival in HER-2 (+) advanced gastric cancer (AGC). Pan-HER inhibitor shows significant antitumor effects in in vitro

Background

and xenograft model of HER-2 (+) gastric cancer. The aim of this study was to find the efficacy/safety of Dacomitinib (PF-00299804), a pan-HER inhibitor, in HER-2 (+) AGC patients.

Methods

We enrolled AGC patients with HER-2 FISH (+) or HER-2 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 end point was 4 month-progression free survival rate (4m-PFS). PK and PD studies 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 toxic effects were skin rash, diarrhea, and fatigue, but most of them were grade ½ Grade 3 skin rash and diarrhea were observed in 2 and 1 patients, respectively. There was no treatment-related death.

Conclusions

Considering the heavily pretreated nature of enrolled patients, Dacomitinib is active and safe treatment option in HER-2 (+) AGC patients. The results of PK and PD studies will also be presented at the meeting.

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