Abstract Background: In locally-advanced resectable squamous cell carcinoma of the head and neck (SCCHN), patients treated with neoadjuvant chemotherapy with major pathologic response (MPR) or pathologic complete response (pCR) have overall survival (OS) rates superior to those of patients with poorer pathologic responses. To improve efficacy, we added the PD-1 inhibitor, nivolumab, to neoadjuvant chemotherapy and evaluated the combination. Methods: In this single-arm, open-label phase II trial, patients with newly-diagnosed stage III–IV HPV-negative SCCHN in the oral cavity, oropharynx, hypopharynx, and larynx or stage II–III HPV-positive oropharyngeal SCCHN received neoadjuvant carboplatin and paclitaxel (6 weeks) plus nivolumab (every other week) followed by surgery and adjuvant radiotherapy+/-chemotherapy. Primary endpoint was pCR at the primary site. Results: Thirty-four patients were enrolled and received neoadjuvant therapy. Thirty-three patients received surgery (R0 resection=100%). Disease sites included the oral cavity (79%), oropharynx (12%), hypopharynx (6%), and larynx (3%). Twenty-eight (85%) patients had stage IVA disease. Median postsurgical follow-up was 35.3 months. Fourteen (41%) patients experienced Grade 3/ 4 treatment-related adverse events. Twenty-seven (82%) patients completed all cycles of neoadjuvant therapy. Twenty-four (73%) patients had at least an MPR at the primary site, and 15(45%) had a pCR. In an unplanned analysis at 3-years, recurrence-free survival and OS were 74% and 83%, respectively. Conclusions: This phase II trial of neoadjuvant nivolumab plus carboplatin and paclitaxel in previously untreated, locally-advanced, resectable SCCHN was well tolerated and reached its primary endpoint of pCR at the primary site. A phase III confirmatory study is warranted in advanced-stage, resectable HPV-negative SCCHN.
Zinner et al. (2025) studied this question.