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Poster display session

137P - Significant benefit of pyrotinib combined with SHR6390 in patients with multiline-resistant HER2-positive advanced gastric cancer


23 Nov 2019


Poster display session


Tumour Site

Gastric Cancer


Zuhua Chen


Annals of Oncology (2019) 30 (suppl_9): ix42-ix67. 10.1093/annonc/mdz422


Z. Chen, Y. Xu, J. Gong, M. Zhang, T. Tian, X. Zhang, C. Zhang, J. Gao, L. Shen

Author affiliations

  • Department Of Gastrointestinal Oncology, Peking University Cancer Hospital-Beijing Cancer Hospital, 100142 - Beijing/CN


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Abstract 137P


The aim of the present study was to explore the mechanism underlying the poor efficacy of pyrotinib, propose and validate a strategy for pyrotinib-combined therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC).


Human GC cell lines and patient-derived xenograft (PDX) models were used to evaluate the antitumor activity and mechanisms of pyrotinib. One pyrotinib-refractory PDX model was established to explore the potential mechanisms underlying drug resistance, propose an optimal therapeutic strategy, and further validate in a phase I clinical trial (NCT03480256).


Pyrotinib exerted strong antitumor activity in HER2-positive GC cells and PDX models via suppressing the activation of the AKT/S6 signaling pathway. In addition, dysregulation of the cell cycle, represented by aberrant activation of the CCND1-CDK4/6-Rb axis, was found in the pyrotinib-refractory PDX model compared with the parental model. Then, combination therapy of pyrotinib with a CDK4/6 inhibitor (SHR6390) was proposed and its strong tumor growth inhibition was observed in the pyrotinib refractory-PDX model. Three HER2-positive GC patients after multiline therapies were subsequently enrolled in our clinical trial treatment with pyrotinib (400 mg/d for 28 days per cycle) combined with SHR6390 (100 mg/d for 21 days per cycle). After two cycles of therapy, two patients achieved a partial response (PR) and one patient achieved decreased stable disease (SD) with a progression-free survival of 120, 199, and 110 d, respectively. The common adverse events included leucopenia (grade 2 to 3), neutropenia (grade 2 to 4), anemia (grade 1 to 3), and thrombocytopenia (grade 1).


This representative translational study suggests that a combination treatment of pyrotinib with SHR6390 may serve as a promising strategy for patients with HER2-positive GC after systematic treatment failure. The optimal drug doses and tolerability of this combination treatment will be explored in future studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Zuhua Chen.


The National Key Research and Development Program of China (No. 2017YFC1308900, 2017YFC0908400).


All authors have declared no conflicts of interest.

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