Nivolumab Plus Ipilimumab Promising For Some Biliary Tract Cancers

Author: By Shreeya Nanda, Senior medwireNews Reporter

medwireNews: Patients with advanced gallbladder carcinoma or intrahepatic cholangiocarcinoma could benefit from combination treatment with nivolumab and ipilimumab, suggest phase II trial findings.

“The promising activity suggests that this combination may be the preferred immunotherapy regimen for further study in biliary tract cancers”, write Oliver Klein, from the Olivia Newton-John Cancer Centre in Heidelberg, Victoria, Australia, and co-investigators.

They report on the subgroup of patients with advanced biliary tract cancers enrolled in the Australian CA209-538 trial aiming to identify treatment options for rare cancers. Participants received four doses of nivolumab 3 mg/kg alongside ipilimumab 1 mg/kg every 3 weeks, followed by nivolumab alone at a dose of 3 mg/kg every 2 weeks for up to 2 years.

In all, 23% of the 39 patients achieved an objective response; all responses were partial and the median duration of response was unreached at the time of analysis. A further 21% had stable disease, giving a disease control rate of 44%.

The median progression-free and overall survival durations were 2.9 and 5.7 months, respectively.

“The response rate in the present study trial compares favorably with the modest activity that has been observed with single-agent anti–PD-1 therapy in patients with advanced [biliary tract cancer] in early clinical trials”, say the researchers, but add that “further investigation will be required in a larger patient population.”

Of note, responses were observed only among patients with gallbladder carcinoma (n=13) and those with intrahepatic cholangiocarcinoma (n=16), with an objective response rate of 31% in each subgroup. None of the 10 patients with extrahepatic cholangiocarcinoma had a response to the combination.

Similarly, there were no responses among the six patients who had not received prior systemic therapy for advanced disease.

Oliver Klein and colleagues highlight that around a fifth of participants experienced disease progression during induction therapy and received just one or two doses of the combination, “which may reflect the aggressive biology and poor prognosis of patients with advanced [biliary tract cancer] at later stages of their disease and the delayed response kinetics of immunotherapy.”

But they acknowledge that “a negative impact of checkpoint inhibition leading to accelerated tumor growth in this patient population, as has been recognized in other cancers, cannot be excluded.”

As reported in JAMA Oncology, immune-related adverse events of any grade occurred in 49% of all patients, while 15% experienced events of grade 3 or worse.

This latter rate “is slightly lower than that seen in other clinical trials using the same dosing regimen, which may be due to the limited drug exposure of the subgroup of patients who experienced rapid disease progression”, comment the study authors.

Reference

Klein O, Kee D, Nagrial A, et al. Evaluation of combination nivolumab and ipilimumab immunotherapy in patients with advanced biliary tract cancers. Subgroup analysis of a phase 2 nonrandomized clinical trial. JAMA Oncol; Advance online publication 30 July 2020. doi: 10.1001/jamaoncol.2020.2814