Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study.

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.

A real-world data of Immune checkpoint inhibitors in solid tumors from India.

BACKGROUND: Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors. METHODS: This was a single center retrospective analysis of prospective data base of patients with non-melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints. RESULTS: Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non-small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non-melanoma solid malignancies was 5.37 months (95% CI, 3.73-9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73-3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%. CONCLUSION: Real-world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non-melanoma solid tumors.