Trastuzumab Biosimilar Plus FOLFOX Shows Promise for HER2-Positive Biliary Tract Cancers

A trastuzumab biosimilar plus modified FOLFOX (oxaliplatin, leucovorin, fluorouracil) chemotherapy in the second- or third-line setting demonstrated promising activity and a manageable safety profile for patients with HER2-positive biliary tract cancer, according to results of a phase 2 trial.

In this open-label, single-arm, multi-institutional trial, 34 patients with HER2-positive biliary tract cancers (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer) who had progressed on chemotherapy were enrolled between June 26, 2020, and September 1, 2021. In the first cycle, patients received 6 mg/kg trastuzumab-pkrb intravenously on day 1, and FOLFOX on days 1 and 2. For all subsequent cycles, patients received 4 mg/kg trastuzumab-pkrb intravenously and FOLFOX every 2 weeks. Treatment continued until disease progression or unacceptable toxicity. 

The primary end point was objective response rate (ORR) in all participants who completed at least 1 cycle. Secondary end points included progression-free survival (PFS), disease control rate, overall survival (OS), and safety.

At the data cutoff date of May 1, 2022, the median follow-up duration was 13 months, with 3 patients remaining on treatment. The ORR was 29.4% (95% confidence interval [CI], 16.7 to 46.3), with 10 patients achieving partial response, and 17 with stable disease. The disease control rate was 79.4% (95% CI, 62.9 to 89.9). The median PFS was 5.1 months (95% CI, 3.6 to 6.7) and the median OS was 10.7 months (95% CI, 7.9 to not reached).

The most common grade 3 treatment-related adverse events were neutropenia (29%), anemia (15%), and peripheral sensory neuropathy (12%). The most common grade 4 treatment-related adverse event was neutropenia (26%). There were no reports of any treatment-related cardiac toxic effects, or deaths. 

The study authors concluded, “second- or third-line trastuzumab biosimilar plus FOLFOX exhibited promising activity with acceptable toxicity, warranting further investigation.”

Source:

Lee CK, Chon HJ, Cheon J, et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: A multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14). Lancet Gastroenterol Hepatol. Published online October 31, 2022. doi:10.1016/S2468-1253(22)00335-1