BACKGROUND Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. METHODS In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. RESULTS The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P = 0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P = 0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. CONCLUSIONS Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636.)

No abstract

Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].).

Background Patients with HPV-positive oropharyngeal squamous cell carcinoma (OPC) have high survival rates when treated with radiotherapy plus cisplatin. Whether replacement of cisplatin with cetuximab, an antibody against the epidermal growth factor receptor, can preserve high survival rates and reduce treatment toxicity is unknown. Methods In a randomized, non-inferiority, multicenter trial, patients with locoregionally-advanced p16-positive OPC were stratified by American Joint Committee on Cancer T (T1-T2 vs. T3-T4) and N (N0-N2a vs. N2b-N3), Zubrod Performance Status (0 vs. 1), and tobacco smoking history (≤ vs. >10 pack-years) and randomized 1:1 to radiotherapy plus cetuximab 400 milligrams per square meter of body surface area (mg/m2), followed by 250 mgs/m2 for seven weekly doses or cisplatin 100 mgs/m2 for two doses, 21 days apart. The sample size was 800 eligible patients. The primary endpoint was overall survival (OS) with non-inferiority margin 1.45 (hazard ratio). Findings From June 2011 through July 2014, 849 patients (805 eligible; 399 cetuximab; 406 cisplatin) were randomized at 182 centers in the United States and Canada. With median follow-up 4·5 years, radiotherapy plus cetuximab did not meet the non-inferiority criterion for OS. Estimated 5-year OS was 77·9% (95% confidence interval [CI] 73·4-82·5) in cetuximab group versus 84·6% (95%CI=80·6-88·6) in cisplatin group (hazard ratio [HR], 1·45, 1-sided 95% upper CI, 1·94; non-inferiority p=0·5056; 1-sided log-rank p=0.0163). PFS was significantly lower in cetuximab group than in cisplatin group (HR 1·72, 95%CI=1·29-2·29; 5-year rates, 67·3% vs. 78·4%), and LRF was significantly higher (HR 2·05, 95%CI=1·35-3·10; 5-year rates, 17·3% vs. 9·9%). The rate of moderate-to-severe toxicity that was acute (77·4% vs. 81·7%, p=0·1586) and late (16·5 vs. 20·4%, p=0·1904) was similar in the cetuximab and cisplatin groups, respectively. Interpretation For patients with HPV-positive OPC, radiotherapy plus cetuximab demonstrated inferior OS and PFS compared to radiotherapy plus cisplatin; toxicity rates were similar (NCT01302834). Funding National Cancer Institute USA, Eli Lilly and The Oral Cancer Foundation

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPVassociated OPSCC for reduced radiation dose as a means of sparing late sequelae. MethodsPatients with HPV16 and/or p16-positive, stage III-IV OPSCC received three cycles of IC with cisplatin, paclitaxel, and cetuximab. Patients with primary-site cCR to IC received intensitymodulated radiation therapy (IMRT) 54 Gy with weekly cetuximab; those with less than cCR to IC at the primary site or nodes received 69.3 Gy and cetuximab to those regions. The primary end point was 2-year progression-free survival. ResultsOf the 90 patients enrolled, 80 were evaluable. Their median age was 57 years (range, 35 to 73 years), with the majority having stage T1-3N0-N2b OPSCC and a history of # 10 pack-years of cigarette smoking. Three cycles of IC were delivered to 77 of the 80 patients. Fifty-six patients (70%) achieved a primary-site cCR to IC and 51 patients continued to cetuximab with IMRT 54 Gy. After median follow-up of 35.4 months, 2-year progression-free survival and overall survival rates were 80% and 94%, respectively, for patients with primary-site cCR treated with 54 Gy of radiation (n = 51); 96% and 96%, respectively, for patients with , T4, , N2c, and # 10 pack-year smoking history who were treated with # 54 Gy of radiation (n = 27). At 12 months, significantly fewer patients treated with a radiation dose # 54 Gy had difficulty swallowing solids (40% v 89%; P = .011) or had impaired nutrition (10% v 44%; P = .025). ConclusionFor IC responders, reduced-dose IMRT with concurrent cetuximab is worthy of further study in favorable-risk patients with HPV-associated OPSCC. Radiation dose reduction resulted in significantly improved swallowing and nutritional status.