The ideal sequencing of definitive chemoradiation and immunotherapy for HNSCC is still evolving. In KEYNOTE-412, concurrent and maintenance pembro did not significantly improve EFS compared to standard CRT. IMMUNEBOOST-HPV was a randomized, phase 2 trial that included 62 patients with high risk HPV+ oropharyngeal cancer (T4, N2/3, or >10 year smoking history). They were randomized to receive standard chemoradiation (70 Gy in 33-35 fractions with q3 week cisplatin) with or without 2 cycles of neoadjuvant nivolumab prior to starting CRT. In the induction arm, 6% had a partial response, 80% stable disease, and 14% had progression. The primary endpoint was whether induction nivo compromised delivery of CRT. The primary outcome was not met as 10% of patients in the induction arm received a total of <200 mg/m2 of cisplatin. There was no difference in the rate of PFS at 36 months with the addition of nivo (85.4% v 85%). At 2 years, the cumulative incidence of relapse was 15% with CRT and 7.3% with CRT + nivo. | Mirghani, J Clin Oncol 2026
