Abstract A039: Neoadjuvant combined anti-PD-1 and anti-CTLA-4 inhibitor therapy for locally-advanced resectable head and neck squamous cell carcinoma: systematic review and meta-analysis

Abstract Introduction: For locally advanced head and neck squamous cell carcinoma (HNSCC), definitive chemoradiation therapy, or surgery followed by radiation with or without chemotherapy, are the standard of care treatment options. However, recurrence rates remain high. Neoadjuvant immunotherapy is currently being explored with promising results, including a 2.9% pathological complete response rate (pCR) and a 70-90% disease-free survival (DFS) rate at 1 year with anti-PD-(L)1 therapy. Combining the anti-CTLA-4 to anti-PD-(L)1 could further improve outcomes. Here we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of combined neoadjuvant immunotherapy with anti-CTLA-4 and anti-PD-(L)1. Methods: A literature search was performed on PubMed, Embase, ASCO, ESMO and ClinicalTrials.gov from the date of inception through 07/22/2024. We used MeSH terms and keywords for HNSCC and neoadjuvant immunotherapy. No filters were applied for the search. Data were extracted following the PRISMA guidelines. Only prospective trials were included. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions and risk ratios (RR) with 95% confidence intervals (CI) were computed. Results: A total of 99 HNSCC patients (oral cavity: 62.9%, oropharynx: 23.5%, larynx: 6.8%, hypopharynx: 6.8%) treated with combined neoadjuvant anti-PD-(L)1 and anti-CTLA-4 therapies from five studies were included in this meta-analysis. The median age was 63 years (range, 22-85), and the number of neoadjuvant therapy cycles (range, 1-2) were similar across the studies.. The tumor stages distribution were as follows: 30% stage II, 21% stage III, 40% stage IV, and 9% had recurrent disease . HPV was positive in 33.4% of patients and 72.2% were current/former smokers. The rates of pCR, major pathological response (MPR), and objective response rate (ORR) were 2.83% (95% CI, 1.63-4.90), 7.55% (95% CI, 3.03-18.83), and 10.61% (95% CI, 3.17-35.5), respectively. The 1-year DFS (82.6%) was reported in only 1 study. The 1-year overall survival (OS) ranged from 87% to 95.7%. No surgical delays were reported and all the patient received the surgery. The rate of grade >3 treatment-related adverse events was 7.29%. (95% CI, 2.30-23.48). The most frequently reported grade 3 adverse events included ALT increase (n=5), followed by diarrhea/colitis (n=4), GGT increase (n=4), and infusion/allergic reaction (n=2). Conclusions: The findings suggest that combining anti-CTLA-4 to anti-PD-(L)1 in the neoadjuvant setting do not deepen the pathological responses seen with single agent anti-PD-(L)1 when compared to the historical controls. Moreover, longer follow-up is necessary to assess potential differences in DFS and OS. Citation Format: Donghoon Shin, Robin Park, Sunggon Lee, Woo Joo Lee, James Yu, Moazzam Shahzad, Guilherme Rabinowits. Neoadjuvant combined anti-PD-1 and anti-CTLA-4 inhibitor therapy for locally-advanced resectable head and neck squamous cell carcinoma: systematic review and meta-analysis [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A039.