Toripalimab combined with chemotherapy in the treatment of primary tracheal squamous cell carcinoma: a phase II proof-of-concept study.

Background: Despite immunotherapy advancements for many solid cancers, role of first-line immunotherapy for tracheal malignancies is uncertain. This study aimed to evaluate the efficacy and safety of toripalimab with chemotherapy for initially-unresectable locally-advanced tracheal squamous cell carcinoma (SCC). Methods: Six eligible patients (5 males and 1 female) with tracheal SCC who were initially considered unresectable were enrolled from February 2021 to April 2023. Patients received toripalimab (240 mg) and platinum-based chemotherapy for 4 cycles. After 2 cycles of treatment, tumor was revaluated to decide further treatment, including either tracheal resection or continued immunochemotherapy and consolidation radiotherapy. Results: The median length of tumor along the trachea was 48.8 (42.5-53.3) mm. Three patients were staged as T4 and 4 patients had N1 diseases. Treatment-related adverse events (TRAEs) occurred in all patients, most were grade 1, including fatigue (100%), leukopenia (16.7%), hypokalemia (16.7%), and pruritus (16.7%), without serious TRAEs. Clinical down-staging was observed in all 6 patients, with a radiologic complete response rate of 33.3%. Two (33.3%) patients received operation: 1 had pathologic complete response and remained disease-free over 22 months postoperatively, while the other patient had R1 resection and died due to tumor relapse 10 months after diagnosis. The remaining 4 non-surgical patients remained progression-free after a median follow-up of 38.0 months. Conclusions: First-line toripalimab with chemotherapy for locally-advanced tracheal SCC showed a potential efficacy with a tolerable safety profile. Surgical conversion was possible, and further studies are needed to verify these findings, particularly in the neoadjuvant setting.