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The KEYNOTE-689 trial evaluated perioperative pembrolizumab + SOC (surgery + adjuvant RT ± cisplatin) in resectable, locally advanced head and neck squamous-cell carcinoma (HNSCC) that is at least 1% PDL1 positive. The addition of pembrolizumab significantly improved 3-year event-free survival (EFS) in all PD-L1 subgroups: CPS≥10 (59.8% vs 45.9%), CPS≥1 (58.2% vs 44.9%), and the total population (57.6% vs 46.4%). Three-year overall survival (OS) also favored pembrolizumab: CPS≥10 (68.2% vs 59.2%), CPS≥1 (69.0% vs 60.2%), and total (68.4% vs 61.1%), though OS was not formally tested at this interim. Toxicities were as expected. Bottom line: perioperative pembro is now a part of the treatment paradigm for locally advanced HNCSCC with PDL1 expression.

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.

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.