Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use

Abstract

Purpose: Cetuximab, which modulates immune responses, may affect the efficacy of subsequent immunotherapy. Here, we assessed outcomes with nivolumab, by prior cetuximab exposure, in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) who had experienced progression within 6 months of platinumcontaining chemotherapy. Patients and Methods: In the randomized, open-label, phase III CheckMate 141 trial, patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC) of single-agent chemotherapy, with stratification by prior cetuximab exposure. The primary endpoint was overall survival (OS); additional endpoints were progression-free survival, objective response rate, and safety. Results: In patients with prior cetuximab exposure, the median OS was 7.1 months with nivolumab versus 5.1 months with IC (HR, 0.84; 95% CI, 0.62-1.15); OS benefit with nivolumab was maintained across most demographic subgroups. In patients without prior cetuximab exposure, the median OS was 8.2 months with nivolumab versus 4.9 months with IC (HR, 0.52; 95% CI, 0.35-0.77); OS benefit with nivolumab was maintained across patient baseline subgroups including tumor programmed death ligand 1 (PD-L1) expression (<1% or !1%). Grade 3-4 treatment-related adverse event rates favored nivolumab versus IC in both subgroups. Conclusions: Nivolumab appeared to improve efficacy versus IC regardless of prior cetuximab use, supporting its use in patients with R/M SCCHN with or without prior cetuximab exposure. The reduction in risk of death with nivolumab compared with IC was greater in patients without prior cetuximab exposure versus with prior cetuximab exposure.

HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING

“…The viral epitopes were considered to be highly immunogenic. However, the clinical response of HPV + HNSCC to checkpoint immunotherapy is surprisingly low (8). In fact, HPV + HNSCC con-ysis performed.…”

“…A 2-year long-term follow-up of a randomized phase III trial (CheckMate 141) showed that HNSCC patients can benefit from anti-PD-1 therapy regardless of the HPV status. Notably, the hazard ratios (HRs) were almost identical between the HPVand HPV + groups, despite the generally more favorable response profiles to chemotherapy among patients with HPV + tumors (7,8). Similarly, pembrolizumab resulted in little survival improvement over standard of care in patients with p16 + tumors enrolled in another randomized phase III trial,…”

CD8 infiltration is associated with disease control and tobacco exposure in intermediate-risk oropharyngeal cancer

“…This effect was consistent across racial groups 35 , and matches long term results from both RTOG0129 and RTOG0522 11 . The introduction of immunomodulatory agents for OPSCC represents both an opportunity to improve clinical outcomes and a challenge in terms of stratifying patients to the appropriate treatment regimen and intensity [36][37][38][39][40] . Several clinical trials, including CheckMate 141 have now demonstrated substantial effectiveness of immunomodulatory agents both in the single agent setting and when combined with chemotherapy with a potentially more pronounced effect in p16+ tumors 36,38 .…”

Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1intTim-3–CD8+ T cells

“…Erb-IL21 synergizes with checkpoint blockade to control advanced tumors. In recent decades, antibodies targeting PD-1, Tim-3, and CTLA-4 inhibitory receptors have led to new effective immunotherapies for patients with advanced cancer (64)(65)(66)(67)(68)(69). Although such therapies have shown additive effects in the clinic, 70%-80% of clinical patients are initially resistant to anti-PD-1 treatment, and more than half of the responsive patients eventually relapse (70).…”