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.
Year: 2025
Type: conference-abstract
Abstract: 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 .
Source: Journal of Clinical Oncology
Authors: Ilya Pokataev, Olesia Stativko, Sergey Kravtsov, Marina Lyadova, Sergey Parts, Evgenia Kuzmina, Daniil Stroyakovskiy, Lyudmila Zhukova, Polina Sergeevna Feoktistova, Margarita Nosova, Tatyana Strelnikova, Rosanna Sydykova, Kristina Lisitsyna, Magomed Dolov, Anna Tedeeva, Ann Semenova, Tatiana Antonova, Sergei Iugai, Vsevolod Galkin
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410804971