Afatinib treatment for her-2 amplified metastatic colorectal cancer based on patient-derived xenograft models and next generation sequencing

ABSTRACT

Background: Substantial progress has been made in metastatic colorectal cancer (mCRC) treatment, but there is still a fraction of patients cannot find any effective therapeutic strategy after guideline-recommended standard chemotherapy and molecular targeted therapy.

Case presentation: Here we present a KRAS/NRAS/BRAF wild-type mCRC patient who has been previously treated with FOLFIRI (fluorouracil, leucovorin, and irinotecan), XELOX (capecitabine and oxaliplatin), cetuximab and bevacizumab, and then received the next generation sequencing (NGS) and whose metastatic subcutaneous nodule was resected to generate patient-derived xenograft (PDX) models. The NGS revealed HER-2 amplification as well as an activating mutation S310F and PDX models tested several drugs finding that afatinib was the optimal agent with notable efficacy and well tolerance among 6 regimens. Therefore, this patient started to take afatinib orally and achieved 3 months progression-free survival (PFS) and relief of clinical symptoms without severe adverse effects.

Conclusions: NGS and PDX models have great significance for precision and individualized medicine in the mCRC treatment, especially for patients whose diseases have been progressed after multiline standard therapies.

Keywords:

• Patient-derived xenograft models
• next generation sequencing
• afatinib
• colorectal cancer
• individual therapy
• case report

Disclosure statement

Disclosure of potential conflicts of interest: No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported by National Key R&D Program of China under Grant 2017YFC0908200; Natural Science Foundation of China under Grant 81101580; and Zhejiang Provincial Natural ScienceFoundation of China under Grant No. LY16H160027.