Efficacy of trastuzumab beyond progression as second-line chemotherapy for HER2-positive advanced gastric cancer

Abstract

Efficacy of trastuzumab beyond progression as second-line chemotherapy for HER2-positive advanced gastric cancer Yasuyoshi Sato, Hiroharu Yamashita, Koichi Yagi, Susumu Aikou, Masato Nishida, Yoshiharu Takenaka, Sachiyo Nomura, Yasuyuki Seto Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Background: Trastuzumab plus fluoropyrimidine and cisplatin have been established as the standard first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). While a survival benefit of continuing trastuzumab beyond progression (TBP) has been shown for HER2-positive breast cancer, efficacy for HER2-positive AGC has yet to be demonstrated. We examined the efficacy of TBP as the second-line chemotherapy for HER2-positive AGC. Patients and methods: We retrospectively reviewed the medical records of 21 patients with HER2-positive AGC treated with trastuzumab plus fluoropyrimidine and cisplatin as the first-line therapy during the period from June 2011 to May 2015 in our department. A total of 13 patients received TBP with chemotherapy as the second-line therapy. The Kaplan–Meier method with a log-rank test was applied to evaluate overall survival (OS) and progression-free survival (PFS). Results: The median OS and PFS with TBP after administration of the second-line therapy were 9.2 months (95% CI, 4.3–11.9 months) and 3.6 months (95% CI, 1.5–3.9), respectively. The median OS after the first-line therapy was 13.3 months (95% CI, ­8.2–19.5 months) in this population, significantly shorter than those in the remaining 10 patients not given TBP as the second-line therapy (not reached; 95% CI, 11.5 months–not available [NA]; p=0.025). Four patients with good tumor shrinkage after the first-line therapy received conversion surgery and had a good survival rate, which was markedly superior to those of patients without surgery, including the TBP population. Conclusion: TBP for HER2-positive AGC seems unlikely to provide a survival benefit in patients with tumors refractory to trastuzumab-containing first-line therapies. Keywords: gastric cancer, HER2, trastuzumab, beyond progression, second-line treatment