Liquid biopsy and multi-analyte testing guided treatment of HER2 positive periampullary adenocarcinoma with durable complete response after trastuzumab based therapy
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Rajnish Nagarkar1, Darshana Patil2, Sewanti Limaye3, Pradip Devhare2, Ashwini Ghaisas2, Navin Srivastava2, Sachin Apurwa2, Sanket Patil2, Jinumary John2, Zarrine Raazi2, Aditya Shreenivas4, Janani Sambath5,6, Ajay Srinivasan2, Prashant Kumar2,5,6, Dadasaheb Akolkar2 and Rajan Datar2
1 HCG Manavata Cancer Centre, Nasik, Maharashtra, India
2 Datar Cancer Genetics Limited, Nasik, Maharashtra, India
3 Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
4 Department of Medical Oncology, Medical College Wisconsin, WI, USA
5 Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India
6 Manipal Academy of Higher Education, Manipal, Karnataka, India
Keywords: periampullary adenocarcinoma; ETA; HER2; trastuzumab
Received: August 13, 2020 Accepted: October 10, 2020 Published: November 10, 2020
Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum. Surgical resection followed by adjuvant therapy is considered as the standard of care treatment for these carcinomas. Despite several advances in diagnostics and therapeutics, only 5% of these patients have an overall survival of five years or more. Currently, there is a dearth of viable therapeutic targets for this disease. The role of HER2 in cancer biology has been studied extensively in several tumour subtypes, and HER2 based targeted therapies have shown to have therapeutic benefits on different cancers. In this case report, we present a case of HER2 positive distal common bile duct carcinoma – a subtype of periampullary carcinoma with multiple relapses where multi-analyte testing with Encyclopedic Tumor Analysis (ETA) (Exacta®) identified amplification and over expression of HER2 gene which was used as a potential target to treat the patient with trastuzumab. Synchronous in vitro chemosensitivity profiling on Circulating Tumor Asscociated Cells (C-TACs) isolated from blood aided us to design the personalized chemotherapeutic regimen with cyclophosphamide and methotrexate. The combination of trastuzumab with cyclophosphamide and methotrexate yielded excellent treatment response with the patient remaining in complete response till the last follow-up. Our study suggests HER2 directed therapy as a potent pathway for treatment in the subset of HER-2 amplified distal common bile duct carcinomas.
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