Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742)

Abstract

Purpose This multinational study evaluated the antitumor activity of nivolumab in nasopharyngeal carcinoma (NPC). Tumor and plasma-based biomarkers were investigated in an exploratory analysis. Patients and Methods Patients with multiply pretreated recurrent or metastatic NPC were treated with nivolumab until disease progression. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity. The expression of programmed death-ligand 1 (PD-L1) and human leukocyte antigens A and B in archived tumors and plasma clearance of Epstein-Barr virus DNA were correlated with ORR and survival. Results A total of 44 patients were evaluated and the overall ORR was 20.5% (complete response, n = 1; partial response, n = 8). Nine patients received nivolumab for > 12 months (20%). The 1-year overall survival rate was 59% (95% CI, 44.3% to 78.5%) and 1-year progression-free survival (PFS) rate was 19.3% (95% CI, 10.1% to 37.2%). There was no statistical correlation between ORR and the biomarkers; however, a descriptive analysis showed that the proportion of patients who responded was higher among those with PD-L1 positive tumors (> 1% expression) than those with PD-L1-negative tumors. The loss of expression of one or both human leukocyte antigen class 1 proteins was associated with better PFS than when both proteins were expressed (1-year PFS, 30.9% v 5.6%; log-rank P = .01). There was no association between survival and PD-L1 expression or plasma Epstein-Barr virus DNA clearance. There was no unexpected toxicity to nivolumab. Conclusion Nivolumab has promising activity in NPC and the 1-year overall survival rate compares favorably with historic data in similar populations. Additional evaluation in a randomized setting is warranted. The biomarker results were hypothesis generating and validation in larger cohorts is needed.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

“…The study authors suggested a higher proportion of patients received three or more prior chemotherapy regimens than equivalent trials investigating R/M NPC. As per Table , their proportion is comparable to the nivolumab NCI‐9742 trial, but slightly higher than the camrelizumab monotherapy trial …”

“…( a ) Overall progression‐free survival (PFS) analysis for all four studies. Fang Combination Camrelizumab (Top L), Fang Monotherapy Camrelizumab (Top R), Ma Nivolumab (Bottom L), Hsu Pembrolizumab (Bottom R) . ( b ) Overall PFS based on the two studies with similar inclusion criteria and study characteristics.…”

“…( b ) Overall PFS based on the two studies with similar inclusion criteria and study characteristics. Pembrolizumab (KEYNOTE‐028) trial RED (bottom) line; Nivolumab trial (NCI‐9742) BLUE (middle) line (HLA expressing), YELLOW (top) line (loss of HLA‐A or HLA‐B). [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Endemic NPC cases (WHO class 2/3) are associated with EBV and subsequently demonstrate a low tumour mutation burden . Given the information above, this observation may suggest a reason to be cautious regarding early anti‐PD1 clinical outcomes for the published NPC trials . Somewhat paradoxically, two recent studies, for HPV and polyomavirus associated cancers, respectively, report superior overall survival in patients undergoing anti‐PD1 treatment despite having low tumour mutation rates.…”

“…To illustrate this, Figure shows a marked improvement in PFS for the nivolumab NCI‐9742 trial when stratified by loss of HLA expression (1 year PFS 76% [yellow line] vs . 30% [blue line]) . However, the latter observation may be counter‐intuitive, as loss of MHC class I (HLA A + B) expression should lead to failure of CD8 + T cell attack.…”