Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient

Abstract

Background: Trastuzumab plus chemotherapy remains the standard first-line treatment strategy for HER2-positive gastric cancer (GC). Trastuzumab resistance, on the other hand, remains a significant issue. There are a few effective anti-HER2 agents for patients who develop resistance to trastuzumab.

Case presentation: A 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg). After treatment for 6 months, the patient achieved complete response (CR) with PFS up to 21 months. After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment. She started to receive third-line treatment of irinotecan (200 mg d1) and capecitabine (60 mg bid) plus pyrotinib (400 mg/day). After 2 months of treatment, the tumor is evaluated as partial response with PFS of 12 months.

Conclusions: We presented a patient with HER2-positive GC who benefited from the pyrotinib-based treatment after two lines of trastuzumab-based therapies failed. Further research is required to validate such conclusions.

Keywords: HER2; gastric cancer; pyrotinib; resistance; trastuzumab.

Figure 1

(A) The treatment procedure of the 49-year-old female with stage IV GC. GC, gastric cancer; PFS, progression-free survival; PD, progressive disease. (B) The results of chest computed tomography (CT) scans suggested that liver and lung lesions were reduced in size after first-line treatment. (C) CT results at first relapse in March 2019 and after surgical operation (R0 resection) in September 2019. (D) Fluorescence in situ hybridization (FISH) images demonstrated HER2 amplification. (E) NGS analysis of tumor tissue at diagnosis (pre-resistance) and first relapse (post-resistance). (F) The CT results following second relapse suggested the tumor shrank with third-line treatment. March 2020, Baseline; June and August 2020, during tumor remission; March 2021, tumor progression. (G) The ctDNA status during tumor remission and disease progression.