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).
The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048.
Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS < 1 and CPS 1-19 subgroups were performed.
Of 882 participants enrolled, 128 had PD-L1 CPS < 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS < 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]).
Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1–expressing HNSCC.
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.
Although immunotherapy did not beat chemotherapy but was non inferior and with more favorable safety.
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.
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.
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