A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer.

Objectives: Cisplatin-based chemoradiation is an established organ-preserving strategy for locally advanced laryngeal cancer, but long-term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods: This trial was an open-label, single-arm, multi-institutional study with a Phase I run-in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2-3; N0-3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2-3 weeks prior to chemoradiation and then, q21 days concurrently with high-dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ-preservation rate (OPR) at 18 months. Results: A total of nine patients were enrolled with a median follow-up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12-month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 ( Conclusion: UCCI-HN-15-02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long-term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow-up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575.Level of evidence: 2b.