Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study.

Autor:	Powell SF; Sanford Cancer Center, Sanford Health, Sioux Falls, SD., Gold KA; Moores Cancer Center, University of California San Diego, La Jolla, CA., Gitau MM; Roger Maris Cancer Center, Sanford Health, Fargo, ND., Sumey CJ; Sanford Cancer Center, Sanford Health, Sioux Falls, SD., Lohr MM; Sanford Cancer Center, Sanford Health, Sioux Falls, SD., McGraw SC; Sanford Cancer Center, Sanford Health, Sioux Falls, SD., Nowak RK; Sanford Cancer Center, Sanford Health, Sioux Falls, SD., Jensen AW; Roger Maris Cancer Center, Sanford Health, Fargo, ND., Blanchard MJ; Roger Maris Cancer Center, Sanford Health, Fargo, ND., Fischer CD; Radiology, Sanford Health, Sioux Falls, SD., Bykowski J; Moores Cancer Center, University of California San Diego, La Jolla, CA., Ellison CA; Sanford Research, Sanford Health, Sioux Falls, SD., Black LJ; Sanford Research, Sanford Health, Sioux Falls, SD., Thompson PA; Sanford Research, Sanford Health, Sioux Falls, SD., Callejas-Valera JL; Sanford Research, Sanford Health, Sioux Falls, SD., Lee JH; ImmunityBio, Culver City, CA., Cohen EEW; Moores Cancer Center, University of California San Diego, La Jolla, CA., Spanos WC; Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2020 Jul 20; Vol. 38 (21), pp. 2427-2437. Date of Electronic Publication: 2020 Jun 01.
DOI:	10.1200/JCO.19.03156
Abstrakt:	Purpose: Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC. Patients and Methods: Eligible patients included those with oral cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. Pembrolizumab was administered concurrently with and after chemoradiotherapy with weekly cisplatin. Safety was the primary end point and was determined by incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy completion. Key secondary end points included overall (OS) and progression-free survival (PFS). Results: The study accrued 59 patients (human papillomavirus [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, all of which occurred during concurrent chemoradiotherapy; 98.3% of patients completed the full planned treatment dose (70 Gy) of radiotherapy without any delays ≥ 5 days; 88.1% of patients completed the goal cisplatin dose of ≥ 200 mg/m 2 . EOT CR rates were 85.3% and 78.3% for those with HPV-positive and -negative HNSCC, respectively. Conclusion: Pembrolizumab in combination with weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support further investigation of this approach.
Databáze:	MEDLINE
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