Although immunotherapy did not beat chemotherapy but was non inferior and with more favorable safety.
CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations.
Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME.
CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.
Based on these findings, Carbo/Taxol+Pembro is an active regimen in met-HNC and an option for those patients who are not good candidates for 5FU based therapy.
Pembro with chemotherapy or alone better then cetuximab combination, also improved responses to subsequent therapy.
Phase II/III study of weekly docetaxel+RT vs. RT alone in cis-ineligible patients. This study was done in India, where oral cancers are an epidemic and possibly biologically unique, as most are related to the use of oral tobacco + betel nut products. >70% of patients were stage IVA / IVB, and HPV was only positive in 4% of patients. Still, the survival benefit was sizeable, and the treatment was tolerable. This is a good option for cis-ineligible HPV-neg patients with bulky disease.
Again, further evidence of continued efficacy and tolerability of IO and IO/chemotherapy in SCCHN as compared to EGFR-blockade/chemotherapy. The PD-L1 negative space remains a more difficult scenario, hence new biomarkers are critically important. The long-term response and CR of a percentage of patients are real and intriguing (patient characteristics leading to such response).
Given relatively low-toxicities of capecitabine, it is reasonable to consider it especially in a population with fewer comorbidities and preserved performance-status. More data pertaining OS differences will be welcome. Study is relatively small but not unusual for this diagnosis.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
