Real-world effectiveness of third- or later-line treatment in Japanese patients with HER2-positive, unresectable, recurrent or metastatic gastric cancer: a retrospective observational study

BACKGROUND: Real-world evidence on the preference for and effectiveness of third- or later-line (3L +) monotherapy for HER2-positive gastric cancer is limited in Japan. This study evaluated the utility of nivolumab, irinotecan, and trifluridine/tipiracil (FTD/TPI) monotherapy as 3L + treatment in Japanese patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer who were previously treated with trastuzumab. METHODS: In this multicenter, retrospective, observational study (20 centers), data of eligible patients were extracted from medical records (September 22, 2017–March 31, 2020), with follow-up until June 30, 2020. Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate (ORR; complete response [CR] + partial response [PR]), and disease control rate (DCR). RESULTS: Of 127 enrolled patients, the overall analysis population comprised 117 patients (median [range] age, 71 [38–89] years). The most commonly prescribed 3L + monotherapy was nivolumab (n = 100), followed by irinotecan (n = 12) and FTD/TPI (n = 5). The median (95% confidence interval [CI]) OS, rwPFS, and TTF were 6.2 (4.5–8.0), 1.9 (1.5–2.3), and 1.8 (1.5–2.2) months, respectively, at median (range) 150 (25–1007) days of follow-up. The ORR (CR + PR) and DCR were 9.0% (1% + 8%) and 32.0%, respectively. Factors such as higher neutrophil–lymphocyte ratio (≥ 2.54), Glasgow prognostic score (≥ 1), Eastern Cooperative Oncology Group performance status (ECOG PS; ≥ 2), and hepatic metastasis significantly impacted OS. CONCLUSIONS: The observed OS in this study for HER2-positive G/GEJ cancer was shorter than that reported previously, suggesting that the effectiveness of nivolumab, irinotecan, or FTD/TPI as 3L + therapy may be limited. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10147-022-02162-4.