Citations 1
Targeting HER2 mutant advanced biliary tract cancers with neratinib: results from the SUMMIT ‘basket’ trial
Harding, James J. , Shah, Ronak , Murphy, Jessica, Cleary, James M. , Shapiro, Geoffrey I. , Moreno, Víctor , Loi, Sherene , Spanggaard, Iben , Park, Haeseong , Stemmer, Salomon M. , DiPrimeo, Daniel, Savin, Casey , Selçuklu, S. Duygu , Berger, Michael , Moreno, Victor , Loi, Sherene , Shapiro, Geoffrey I , Harding, James J , Piha‐Paul, Sarina A. , Quinn, David I , Braña, Irene , Borad, Mitesh J. , Ford, James M. , Arnedos, Mónica , Fouchardière, Christelle de la , Fountzilas, Christos , Zhang, Jie , Eli, Lisa D. , Meric‐Bernstam, Funda , Jhaveri, Komal , Solit, David B. , Abou‐Alfa, Ghassan K.
No container title available | May 11, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has activity in HER2-mutant tumours. SUMMIT is an open-label, single-arm, multi-cohort, phase 2, ‘basket’ trial of neratinib in patients with solid tumours harbouring oncogenic HER2 somatic mutations (NCT01953926). The primary objective of the BTC cohort was objective response rate (ORR). Among 25 treatment-refractory patients (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers), the ORR was 16%. The most common HER2 mutations were S310F (n = 11; 48%) and V777L (n = 4; 17%). Outcomes appeared worse for ampullary tumours or those with co-occurring oncogenic TP53 and CDKN2A alterations. Loss of amplified HER2 S310F and acquisition of multiple previously undetected oncogenic co-mutations were identified at progression in one responder. Neratinib demonstrated anti-tumour activity in patients with refractory BTC harbouring HER2 mutations. Future studies of rational combinations are warranted.