In a single-center phase II trial (DEPEND) reported in JAMA Oncology, Rosenberg et al found that the combination of neoadjuvant nivolumab and chemotherapy followed by response-stratified chemoradiation (CRT) was active in human papillomavirus (HPV)-negative stage IVa/b head and neck squamous cell carcinoma (HNSCC).
Study Details
In the investigator-initiated trial, 36 patients enrolled at the University of Chicago between September 2019 and June 2022; they received three 21-day cycles of nivolumab at 360 mg on day 1; paclitaxel at 100 mg/m2 on days 1, 8, and 15; and carboplatin AUC = 5 on day 1. The primary outcome measure was deep response rate, defined as at least 50% shrinkage of tumor after neoadjuvant nivolumab plus chemotherapy; a rate of more than 40% would constitute an effective regimen for further testing. Patients with at least 50% reduction received de-escalated CRT to 66 Gy with elimination of elective nodal volumes; patients with less than 50% reduction received standard CRT to 70 to 75 Gy. Adjuvant nivolumab was administered for nine cycles.
Key Findings
Median follow-up was 20 months (range = 13–40 months). The deep response rate was 53% (95% confidence interval [CI] = 35%–70%), meeting the study endpoint. The objective response rate was 86% (95% CI = 71%–95%).
Among 19 patients receiving de-escalated CRT, the estimated 24-month progression-free survival rate was 69% (95% CI = 39%–87%), and the estimated 2-year overall survival rate was 74% (95% CI = 41%–90%). Among 16 patients receiving standard CRT, the estimated 24-month progression-free and overall survival rates were 69% (95% CI = 40%–86) and 79% (95% CI = 47%–93%).
The most common adverse events of any grade observed during CRT in both the de-escalated group and the standard group were mucositis (74% vs 94%), radiation dermatitis (68% vs 88%), and dry mouth (37% vs 63%).
The investigators concluded: “In this phase II nonrandomized clinical trial, neoadjuvant nivolumab/chemotherapy led to deep responses in 53% of patients with HPV-negative … stage IVa/b HNSCC, and response-adapted de-escalated CRT led to favorable survival with lower acute toxic effects among deep responders.”
Ari J. Rosenberg, MD, of the Section of Hematology and Oncology, University of Chicago, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb and Celgene. For full disclosures of the study authors, visit jamanetwork.com.
