Abstract 4067
Background
Inoperable gastric and GEJ cancer is usually treated with platinum- and fluoropyrimidine-based combination chemotherapy. Targeting of the epidermal growth factor family of receptors has been unsuccessful except in the case of HER2 targeting with trastuzumab. Afatinib, has shown activity in preclinical models of gastric cancer and has been combined with cisplatin and 5-FU in phase I studies.
Methods
Patients (pts) were treated with the combination of cisplatin (75 mg/m2 ; day 1), 5-FU (750 mg/m2; continuous infusion days 1-4) and afatinib (40 mg/day; week1: days 3-5, weeks 2, 3: days 1-5), in an effort to optimize therapy efficacy and tolerability. Primary endpoint was the objective response rate (ORR) in the intention to treat (ITT) and the per-protocol (PP) population. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile.
Results
Among the 55 pts (median age 64; range 20-77) enrolled (ITT), the ORR was 34.5% (44.2% in PP pts; N = 43). After a median follow-up of 33.3 months, median PFS and OS were 5 (95% CI 4-6; 49 relapses) and 9.3 (95% CI 6.7-11.5; 43 deaths) months, respectively. Median relative dose intensities administered were 0.97 for 5-FU, 0.96 for cisplatin and 0.94 for afatinib. Grade 3/4 adverse events (AEs) occurred in 34 pts (61.8%) and 9 pts (16.4%), respectively. Most common grade 3/4 AEs were neutropenia (27.3%), anemia (12.7%), hypokalemia (10.9%), diarrhea (5.4%), infections (5.4%). Acneiform rash grade 1/2 was noted in 20% of pts, while there were 4 (7.3%) thromboembolic events (grade 1-3). There were no treatment related deaths. Pts with GEJ cancers had worse OS than pts with gastric cancer (p = 0.03).
Conclusions
The combination of afatinib with cisplatin / 5-FU in pts with inoperable gastric / GEJ cancer has modest activity, however afatinib weekend breaks optimized the compliance and tolerability of the combination. Identification of predictive biomarkers could potentially help in further evaluation of the role of afatinib in gastric / GEJ cancer.
Clinical trial identification
NCT01743365 (December 6, 2012).
Legal entity responsible for the study
Hellenic Cooperative Oncology Group.
Funding
Hellenic Cooperative Oncology Group.
Editorial Acknowledgement
NA
Disclosure
All authors have declared no conflicts of interest.