Background: Although trastuzumab in combination with chemotherapy is the standard first-line (1L) treatment for human epidermal growth factor receptor 2 positive metastatic gastric cancer (HER2+ mGC), effective HER2 targeted therapeutic options beyond 1L are limited. This study aims to examine subsequent treatments in HER2+ mGC patients who had used trastuzumab-based regimen (TBR) as 1L or second-line (2L) treatment in real-world. Methods: A retrospective study was conducted using the IQVIA PharMetrics® Plus Database. Adult patients were included if they had a gastric cancer diagnosis (ICD-9: 151.0-151.9; ICD-10: C16.0-C16.9) followed by a secondary malignancy diagnosis (as indicator of mGC) from 07/01/2014 to 06/30/2019, were continuously enrolled for ≥ 6 months before mGC diagnosis, and subsequently received any anti-HER2 drugs. Treatment patterns were summarized for patients who received subsequent line of therapy after discontinuation of TBR. Discontinuation was defined as a treatment gap ≥ 60 days or initiation of a medication not included in the previous regimen. Results: Among 364 HER2+ mGC patients identified, 344 patients used TBR as either 1L or 2L treatment, 264 of whom used TBR as 1L and 80 used TBR in 2L but not 1L. Of 264 patients who used TBR as 1L, 130 initiated 2L treatment and trastuzumab was used again as 2L in 72 patients. The most common regimens used in 2L post 1L TBR were paclitaxel + ramucirumab (15.4%), FOLFOX + trastuzumab (11.5%), and capecitabine + trastuzumab (11.5%). The median (95% confidence interval [CI]) time to treatment discontinuation of 2L was 2.1 (1.9, 2.8) months. Of 344 patients who used TBR as either 1L or 2L treatment, 98 patients initiated third-line (3L) treatment. Trastuzumab was re-used in 45 (45.9%) patients as 3L treatment. The most common regimens used in 3L post TBR were paclitaxel + ramucirumab (13.3%), pembrolizumab (9.2%), fluorouracil + irinotecan (8.2%), and FOLFIRI + trastuzumab (8.2%). The median (95% CI) time to treatment discontinuation of 3L treatment was 3.3 (2.4, 5.0) months. Conclusion: Despite the lack of evidence for trastuzumab continuation beyond 1L, it was commonly used in later lines of therapy for patients with mGC. Treatment duration of 2L and 3L therapy were short. These findings highlight the need for new effective targeted treatment for HER2+ mGC patients who progressed after trastuzumab.
Summary of treatments after TBR in patients with HER2+mGC

