Antitumour activity was observed when nivolumab was continued post-progression in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed on nivolumab after experiencing prior recurrence within 6 months of platinum-based chemotherapy, according to findings presented during ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.
Robert Haddad of the Department of Medical Oncology, Dana-Farber/Harvard Cancer Center, in Boston, USA, and colleagues quantitated the treatment responses to nivolumab after initial radiologic evidence of progression per RECIST v1.1. was observed among participants in the CheckMate 141 (NCT02105636) trial.
The investigators conducted a biomarker analysis and updated the clinical outcomes in patients in the CheckMate 141 nivolumab arm who met protocol defined criteria, which excluded patients without progression or tumour assessment. Immune cell phenotyping was conducted by flow cytometry and it was associated to clinical response in patients having samples available for both treatment days 1 and 43.
Nivolumab prolonged overall survival compared to standard single-agent therapy
CheckMate 141 was a randomised phase III study in patients with R/M HNSCC that compared nivolumab to investigator’s choice of single-agent systemic therapy in 361 patients with progressive disease occurring within 6 months after platinum-based chemotherapy. Nivolumab was administered at a dose of 3 mg per kilogram every 2 weeks. Overall survival (OS) was determined significantly longer with nivolumab compared to standard single-agent therapy (hazard ratio [HR] 0.70 (97.73% confidence interval [CI] 0.51, 0.96).
At ESMO 2017, findings from an analysis based upon a September, 2016 database lock with a minimum follow-up of 11.4 months were presented. Disease progression was detected in 146 (61%) of 240 patients randomised to nivolumab in CheckMate 141. One or more doses of nivolumab was delivered to 62 (42%) of these patients following progression (TBP group), and 84 (58%) patients were not treated beyond progression (NTBP group).
Updated findings show antitumour activity with nivolumab post-progression in recurrent/metastatic HNSCC
Updated findings showed that median OS was 12.7 months (95% CI 9.7, 14.6) with nivolumab in the TBP group.
After the initial progression, 15 (24%) TBP patients had a reduction in the target lesion size, and 3 patients had a greater than 30% reduction. Of the 15 responding patients, 8 were human papilloma virus (HPV)-positive, 5 had PD-L1 tumour expression ≥1%, and 5 patients had shown a greater than 20% increase in target lesion at the first progression.
Nivolumab showed a safety profile that was in accord with previous reports. The rates of grade 3/4 treatment-related adverse events (TRAEs) were similar in the TBP and NTBP groups.
At day 1, the percentage of PD-1-positive CD8-positive effector T cells was lower in responders and TBP patients . Additionally, on day 1 a lower percentage of PD-1-positive T-regulatory cells was detected in TBP patients, that was similar to the percentage detected in responders.
Nivolumab-treated patients who experienced tumor reduction with treatment beyond progression had some circulating cellular immune profiles that were similar to conventional responders. Nivolumab treatment beyond progression was sooiciated with tumor size reductions, is well tolerated and can be considered in some patients with R/M HNSCC, according to the CheckMate 141 investigators .
The study was supported by Bristol-Myers Squibb.
1043O – Haddad R, et al. Treatment Beyond Progression With Nivolumab in Patients With Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (SCCHN) in the Phase 3 Checkmate 141 Study: A Biomarker Analysis and Updated Clinical Outcomes.