A phase II trial of reirradiation combined with pembrolizumab in patients with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck (HNSCC).
Authors: Dan Paul Zandberg, Jessica R Bauman, Ranee Mehra, Jason K. Molitoris, Mark Jelinek, Hong Wang, David Anthony Clump, Heath Devin Skinner, Robert L. Ferris, Moon Jung Fenton, Kevin J. Cullen, Mohan Suntharalingam, Soren Bentzen, Anshu Giri, Jeffrey C Liu, Thomas James Galloway
Journal: Journal of Clinical Oncology (2024)

6049 Background: Better outcomes are needed for patients (pts) with locoregional inoperable recurrence or second primary HNSCC after prior radiation therapy. Methods: We conducted a phase II single arm trial of hyperfractionated reirradiation (ReRT, 1.2 Gy BID for total 60Gy to gross disease + margin without elective nodal radiation) plus pembrolizumab (P) (200mg q3 weeks starting day 1 of ReRT). P was continued until confirmed CR or if no CR, until disease progression or up to 24 months. All pts underwent a 3 month post ReRT PET/CT and subsequently CT neck/chest after every 3 rd cycle of P. Pts included had: Locoregional recurrence or second primary HNSCC (excluding skin or salivary), were unresectable or not willing to undergo resection, one RT course completed at least 6 months prior, with &gt;50% tumor volume treated at doses &gt;45Gy, ECOG PS 0-1, a target lesion by RECIST, no distant metastasis, and no prior anti-PD-1/PD-L1. Primary endpoint was PFS, and the hypothesis was that the median PFS would increase from the historical control of 8 months (mo) to 12 mo, α=0.05, power 78%, n=48. Secondary endpoints: ORR by RECIST, OS, toxicity, QOL (EORTC). The Kaplan-Meier method was used to estimate PFS and OS. Results: In the 48 evaluable pts, median age was 65.5 (range 44-79), 62.5% male. Primary site: hypopharynx (8.3%), larynx (6.3%), nasopharynx (10.4%), oral cavity (43.7%), oropharynx (31.3%, one HPV+ pt). Median doses of P was 8, median RT dose was 60 Gy and 20.8% received proton RT, remainder IMRT. Median follow up was 49.1 months. The median PFS was 8.3 mo (95%CI 5.5-10.3), and median OS was 13.8 mo (95% CI 9.5-21.8). 1 and 3-year PFS were 28.9% and 22.3% respectively, and for OS 54.2% and 25.7%, respectively. 42 pts were evaluable for response and the ORR was 54.8% (33.3% CR, 21.4%PR), 21.4% SD, 23.8% PD. In an exploratory analysis, the median PFS was 13.8 mo (95% CI 9.1-NR) and the median OS was 57.8 mo (19.6-NR) in patients that had a response (CR/PR, n=23), with a 1 and 3-year PFS of 51.8% and 42.4%, respectively, and for OS 78.3% and 51.7%, respectively. All patients had at least one treatment related AE (TRAE), defined as possibly, probable, or definitely related to treatment. 39% of pts had a G3 TRAE and the most common ones were: aspiration, dehydration, anemia, dysphagia, dyspnea. 4 patients had a G5 TRAE (found down deceased, epistaxis, aspiration pneumonia, iRAE pneumonitis). Conclusions: Our prospective trial uniquely evaluated ReRT plus pembrolizumab in patients with locoregional recurrence/second primary HNSCC that did not undergo salvage surgery. The primary endpoint of PFS was not improved compared to historical control. PD-L1 biomarker analysis is ongoing and will be reported subsequently. Clinical trial information: NCT02289209 .