Neratinib continues to be a potential treatment option for HER2+ive biliary tract cancers

Targeting HER2 mutation-positive advanced biliary tract cancers with neratinib: Final results from the phase II SUMMIT basket trial.  (Abstract # 4079)

On February 2020, the company received Neratinib FDA approval in combination with capecitabine for adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. Neratinib is an irreversible, pan-HER, oral tyrosine kinase inhibitor. The Phase II SUMMIT trial is an open-label, single-arm, multi-cohort, ‘basket’ trial of neratinib breast cancer in patients with solid tumors that harbor oncogenic somatic HER2 mutations. Efficacy results from the BTC cohort of 25 patients (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers) demonstrated an overall response rate (ORR) of 16%, clinical benefit rate of 28%, median progression-free survival (PFS) of 2.8 months and overall survival (OS) of 5.4 months. Median PFS for the gallbladder, cholangiocarcinoma, and ampulla cohorts was 3.7, 1.4, and 1.1 months, respectively. These cohorts' corresponding median OS values were 9.8, 5.4, and 5.0 months, respectively.

The most common HER2 mutations were S310F (n = 11; 48%) and V777L (n = 4; 17%). Exploratory analyses suggested worse outcomes for HER2-mutant tumors with co-occurring oncogenic TP53 and CDKN2A alterations. The most frequently observed toxicity was diarrhea (56% any grade).

KOL insights

 “Previous findings indicate that neratinib has a promising role as a treatment option for rare cancers. With the results from this cohort and others in the SUMMIT trial, we can continue to identify new groups of patients who can benefit from neratinib.” –Expert Opinion.


As Neratinib is tolerable with modest antitumor activity in patients with BTC harboring HER2 mutations. Although the primary endpoint was met, additional studies are needed to determine if combining neratinib with other cancer therapies could significantly extend patients' survival and improve their quality of life.