PURPOSE The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively ( P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively ( P = .744). CONCLUSION To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.

PURPOSE The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival ( P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival ( P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.

PURPOSE Multidisciplinary molecular tumor boards (MTBs) help in interpreting complex genomic data generated by molecular tumor profiling and improve patients' access to targeted therapies. The purpose of this study was to assess the impact of our institution's MTB on the clinical management of patients with cancer. METHODS This study was conducted at a tertiary cancer center in India. Cases to be discussed in the MTB were identified by molecular pathologists, scientists, or oncologists. On the basis of the clinical data and molecular test reports, a course of clinical management was recommended and made available to the treating oncologist. We determined the proportion of patients who were recommended a change in the clinical management. We also assessed compliance of the treating oncologists with MTB recommendations. RESULTS There were 339 discussions for 328 unique patients. The median age of the cohort was 54 years (range 17-87), and the majority of the patients were men (65.1%). Of 339 cases, 133 (39.2%) were recommended continuation of ongoing therapy while the remaining 206 (60.7%) were recommended a change in clinical management. Compliance with MTB recommendations for a change in clinical management was 58.5% (79 of 138 evaluable cases). Compliance and implementation for MTB's recommendation to start a new therapy in 104 evaluable cases were 60.5% and 44.2%, respectively. A total of 248 biopsies had at least one actionable mutation. A total of 646 mutations were identified in the cohort, with EGFR being the most frequently altered gene. CONCLUSION MTBs help in interpreting results of molecular tests, understanding the significance of molecular abnormalities, and assessing the benefits of available targeted therapies and clinical trials in the management of patients with targetable genetic alterations.