Publication

Abstract : Background: Prognosis of Gallbladder cancer (GBC) remains unchanged over the last 20 years. Her2neu amplification is present in 17% of cases of advanced GBC. We present our experience of anti Her2 targeted therapy. Methods: This is a multicenter, prospective, observational study conducted in northern India from Sept2017-Sept2019. All consecutive patients were tested for Her2neu by standard techniques or next-generation sequencing (NGS). Trastuzumab or Lapatinib was used as the anti Her2 therapy along with chemotherapy. Outcome measures were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) and compared to historical controls. Data were censored on 31Dec2019. Results: A total of 181 patients were screened; 38 (20.9%) patients were positive for Her2neu or Her3neu. Demographic details are depicted in the table. Her2 was detected by IHC 18 (47%), FISH 6(15.7%) or NGS 14(36.8%). Five patients were positive for Her3 mutation and/or amplification. Twenty-one patients received anti Her2 therapy upfront with chemotherapy. At a median follow-up of 6.8 months, median PFS was 4.1 months for chemotherapy only (n = 85) and 9.7 months for trastuzumab with chemotherapy (n = 21) (HR 0.22; P < 0.05). The median OS was 14 and 6 months in patients with or without trastuzumab-based therapy (HR 0.08 P = 0.001), respectively. Trastuzumab with chemotherapy was well tolerated. Conclusions: Her2neu directed therapy significantly improve ORR, PFS, and OS in GBC with no added toxicities in the first line. It must be evaluated in a randomized phase 3 clinical trials.