Immune Checkpoint Inhibitor Monotherapy Demonstrates Antitumor Activity in Advanced Biliary Tract Cancer

For patients with advanced biliary tract carcinoma, immune checkpoint inhibitors (ICIs) are well-tolerated and demonstrate modest antitumor activity. Biliary tract cancers have poor prognosis, and the role of immunotherapy treatment in this population is currently undefined.

This single-institution study included 47 patients with advanced biliary tract cancer who received ≥1 dose of an ICI, either a programmed death 1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor, between May 1, 2015, and October 31, 2020. Patients being treated with a combination of ICI and chemotherapy were not included.

The primary end point of the analysis was progression-free survival (PFS) and secondary end points included overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events.

Of the 47 patients in the study, 37 patients had intrahepatic cholangiocarcinoma, 8 had gallbladder carcinoma, and 2 had hilar cholangiocarcinoma. Of the ICIs used, 24 patients received pembrolizumab, 12 received toripalimab, 9 received nivolumab, and 2 received atezolizumab.

The median follow-up duration was 15.9 (95% confidence interval [CI], 6.2 to not evaluable [NE]) months for PFS and 17.2 (95% CI, 8.7 to 27.8) months for OS. The median PFS was 3.7 (95% CI, 2.3 to 6.2) months and the 6-month PFS rate was 34.1% (95% CI, 22.7 to 51.4). The median OS was 6.9 (95% CI, 4.8 to 27.7) months, the 6-month OS rate was 53.2% (95% CI, 40.4 to 70.1) and the 12-month OS rate was 42.5% (95% CI, 29.8 to 60.6). The ORR was 11%, with 1 complete response and 4 partial responses, and the DCR was 53.2%.

For those patients who received an ICI in the first-line setting (n = 11), the ORR was 27% (1 complete response, 2 partial responses) with a median PFS of 6.34 (95% CI, 5.26 to NE) months. The median PFS of those patients who received an ICI at the second- or later-line therapy (n = 36) was 3 (95% CI, 2.1 to 4.1) months, in comparison.

There were tumor mutational burden (TMB) values available for 32 of the patients. While having a TMB ≥5 mut/Mb was associated with a statistically significant increase in PFS when compared to a TMB ≤5 mut/Mb (6.4 vs 2.2 months; P = .0027), there was not a statistically significant increase in OS for the same comparison. Of 8 patients with a TMB > 10 mut/Mb, 2 had a partial response and 6 had stable disease. The PFS was 11.89 (95% CI, 3.52 to NE) months and the OS was 21.2 (95% CI, 7.52 to NE).

There were treatment-related adverse events reported in 81% of patients, largely fatigue (68.1%), nausea (34%), or diarrhea (21.3%). Most adverse events were grade 1/2, with 1 instance of grade 4 myositis, and 1 death due to pneumonitis.

The study authors noted that the phase 3 TOPAZ-1 study, evaluating the PD-L1 inhibitor durvalumab in combination with standard chemotherapy for treatment-naïve patients with advanced biliary tract cancer, “will likely establish chemoimmunotherapy as a first-line treatment option for patients with advanced [biliary tract cancer]. This begs the question if monotherapy with an ICI has a place in the treatment continuum of advanced [biliary tract cancer].”

The authors concluded that their study both “reiterates that ICI monotherapy has modest antitumor activity in patients with advanced [biliary tract cancer]” and “showed an association between improved PFS and higher TMB.”

Source:

Liddel SS, Chakrabarti S, Wintheiser GA, et al. Tumor mutational burden is a potential predictive biomarker for response to immune checkpoint inhibitors in patients with advanced biliary tract cancer. JCO Precis Oncol. Published online June 30, 2022. doi:10.1200.PO.22.00003