Induction pembrolizumab plus cisplatin and 5-FU chemotherapy followed by chemoradiotherapy in locally advanced squamous cell cancer of oropharynx, hypopharynx or larynx: Results of multicenter prospective phase II study.

6070 Background: Chemoradiation with cisplatin or induction chemotherapy with docetaxel, platinum agent and 5-FU are associated with high toxicity. We hypothesized that immunochemotherapy with pembrolizumab and platinum-based chemotherapy followed by chemoradiotherapy (CRT) might be associated with higher clinical efficacy along with a lower likelihood of adverse effects (AE). Methods: We conducted the multicenter single-arm phase II study (NCT05551767), including patients (pts) with stage III-IV, PD-L1 positive (CPS≥1), squamous cell carcinoma of larynx, oropharynx or hypopharynx. Pts with ECOG > 2 were excluded. All enrolled pts received 3 cycles of induction therapy with pembrolizumab 200 mg on day (d) 1, cisplatin 100 mg/m 2 on d1 and 96-hour infusion of 5-FU 1000 mg/m 2 /d followed by CRT. We aimed to evaluate response rate, survival, safety and incomplete CRT rate after induction therapy. Results: Since 2022 to August 2024 120 pts were enrolled, including 82 (72.5%) with oropharyngeal, 21 (17.5%) hypopharyngeal and 12 (10%) laryngeal cancer. The median age was 60 (range 35 - 75), most patients were male (87.5%) and 108 (90%) had ECOG 0-1. Objective response rate (ORR) by RECIST 1.1 was assessed after induction therapy in 116 of 120 pts: 73 (62.9%) pts had response including 19 pts (16.4%) with complete responses (CR). The median change of target lesions was -55% (from -100% to 65%). ORR after CRT was assessed in 102 pts: 84 (82.4%) responders were identified with a 71.6% CR rate. Only 8 (6.7%) pts did not start CRT after induction therapy. Among other 112 pts 92.9% received radiation dose ≥66Gy. With a median follow-up 16.6 months 1-year progression-free survival was 73.5% and 1-year overall survival was 80%. There were no treatment-related deaths on induction therapy although 6 (5%) pts required hospital readmission due to adverse events (AE). The incidence of grade 3-4 AE by CTC AE v.5.0 was 30.8% with asymptomatic neutropenia grade 3-4 being the most frequent AE (23.3%). Conclusions: The study demonstrated promising ORR, progression-free survival rate and acceptable safety profile of induction therapy with pembrolizumab, cisplatin and 5-FU in head and neck cancer. High response rate to induction therapy was associated with a high number of CRT completion. Clinical trial information: NCT05551767 .