Immune checkpoint inhibitors for invasive mucinous adenocarcinoma: A case series

Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma that frequently harbors KRAS mutations and exhibits low programmed death-ligand 1 (PD-L1) expression. As evidence on the use of immune checkpoint inhibitors (ICIs) for IMA is limited, the present study aimed to describe the clinical features, treatment patterns and outcomes to evaluate the effectiveness of ICIs for IMA. The present retrospective study included 15 patients with advanced or recurrent IMA who were treated at Toranomon Hospital (Tokyo, Japan) between April 2014 and March 2025. The present report focuses on 7 patients who received first-line ICI-based therapy. Patient characteristics, molecular and pathological features, treatments administered, and outcomes were summarized, and responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Among the 15 patients, KRAS mutations were identified in 6 patients (40%), PD-L1 expression was positive in 2 patients (13%), negative in 7 patients (47%) and unknown in 6 patients (40%). Of the 7 patients receiving first-line ICI-based therapy, 4 received dual ICIs and 3 received a single-agent ICI. The best overall response among these patients was partial response (PR) in 1 patient (14%), stable disease in 5 patients (71%) and progressive disease in 1 patient (14%). A total of 5 patients (71%) experienced immune-related adverse events leading to treatment discontinuation. In conclusion, first-line ICI-based therapies showed limited effectiveness overall. However, 3 patients treated with dual ICIs and chemotherapy achieved a 100% disease control rate, with 1 patient achieving a PR. Therefore, specific ICI-based combination therapies may be a viable option for the treatment of IMA.