Robert L. Ferris
CHICAGO — Nivolumab continued to confer a significant OS benefit compared with investigator’s choice of therapy among patients with recurrent or metastatic head and neck squamous cell carcinoma, according to long-term data from the phase 3 CheckMate 141 trial presented at American Association for Cancer Research Annual Meeting.
Nivolumab (Opdivo, Bristol-Myers Squibb), a PD-1 checkpoint inhibitor, also maintained a favorable safety profile.
“Long-term prognosis for patients with metastatic HNSCC has historically been poor,” Robert L. Ferris, MD, director of UPMC Hillman Cancer Center, professor of oncology, associate vice chancellor for cancer research and codirector of Tumor Microenvironment Center at University of Pittsburgh, said during a presentation. “Median OS is less than 6 months.”
The CheckMate 141 study included 361 patients with recurrent or metastatic HNSCC who progressed during or after platinum-based therapy.
Ferris and colleagues randomly assigned 240 patients to nivolumab 3 mg/kg every 2 weeks. The other 121 patients received investigator’s choice of therapy, which included methotrexate, docetaxel or the EGFR inhibitor cetuximab (Erbitux, Eli Lilly).
Ten patients assigned investigator’s choice received subsequent immunotherapy.
OS served as the primary endpoint. Secondary endpoints included PFS and safety.
Minimum follow-up was 24.2 months.
Nivolumab appeared associated with significantly improved median OS in the overall population (7.7 months vs. 5.1 months; HR = 0.68; 95% CI, 0.54-0.86) and a higher 2-year OS rate (16.9% vs. 6%).
Ferris and colleagues assessed outcomes based on PD-L1 expression and HPV status.
Results showed nivolumab significantly extended median OS compared with investigator’s choice among patients with PD-L1 expression of 1% or greater (8.2 months vs. 4.7 months; HR = 0.55; 95% CI, 0.39-0.78), those with HPV-positive disease (9.1 months vs. 4.4 months; HR = 0.6; 95% CI, 0.37-0.97) and those with HPV-negative disease (7.7 months vs. 6.5 months; HR = 0.59; 95% CI, 0.38-0.92).
In the subgroup of patients with PD-L1 expression less than 1%, nivolumab-treated patients demonstrated a 27% reduced risk for death at 2 years. Although not statistically significant, the HR trended lower over time as measured at 6 months follow-up (HR = 0.89; 95% CI, 0.54-1.45), 1 year (HR = 0.83; 95% CI, 0.54-1.29) and 2 years (HR = 0.73; 95% CI, 0.49-1.09).
Ferris and colleagues observed complete responses among patients in the higher and lower PD-L1 expression groups.
A higher percentage of patients assigned investigator’s choice of therapy experienced grade 3 or grade 4 treatment-related adverse events (36.9% vs. 15.3%). Researchers reported two (0.8%) toxicity-related deaths in the nivolumab group and one (0.9%) treatment-related death in the investigator’s choice group.
“Nivolumab is the only immunotherapy to significantly improve OS versus investigator’s choice in metastatic HNSCC [after] platinum therapy,” Ferris said. “We conclude that nivolumab is an established therapeutic option for recurrent metastatic head and neck cancer patients.” – by Mark Leiser
Ferris RL, et al. Abstract CT116. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.
Disclosures: Ferris reports clinical trial investigator roles or other relationships with Amgen, AstraZeneca, Benetic Biopharma, Bristol-Myers Squibb, Eli Lilly, EMD Serono, MedImmune, Merck, Pfizer and VentiRx Pharmaceuticals.