Abstract / Summary
Abstract Background Pembrolizumab added to cisplatin and 5-fluorouracil (5FU) lengthens overall survival (OS) relative to chemotherapy alone in non-nasopharyngeal squamous carcinoma of head and neck origin (HNSCC) that is unresectable, relapsed or already spread. Cost restricts this option to fewer than 3% of otherwise eligible patients in India. Indian investigators have reported that an oral metronomic triplet combined with nivolumab 20 mg every three weeks achieves an OS of comparable magnitude. We set out to record what happens clinically when the same antibody is given as 40 mg once every 6 weeks alongside that triplet. Methods An open-label, single-arm, phase III design was adopted. Adults whose HNSCC had relapsed, spread or was inoperable received an oral metronomic triplet [TMC (Methotrexate, Erlotinib, Celecoxib)] of erlotinib 150 mg daily, celecoxib 200 mg two times a day and methotrexate 9 mg/m2 weekly, to which intravenous nivolumab (N) 40 mg was added once every 6 weeks. Median PFS was the primary endpoint; OS, response rate, and response duration were secondary. Results Sixty-five participants received N + TMC; twenty (30.8%) had prior cisplatin exposure. Median PFS was 8.0 months, the 95% CI spanning 7.63–8.37. Complete (CR) and partial (PR) responses together yielded a 6 month response rate of 56.93%, with CR contributing 23.08%. Outcomes did not diverge appreciably by platinum status. One-year survival stood at 37.5%, with a median OS of 11.63 months [95% CI 9.73–13.53]. Median survival reached 11.67 ± 4.81 months in males against 8.72 ± 3.36 months in females (P = 0.014). Fatigue affected sixty-two patients (95.3%); events of grade 3 or worse comprised mucositis (9.23%), anaemia (9.23%) and rash in 4.62%. No immunologic adverse event and no treatment-attributable death occurred. Conclusions In relapsed, metastatic or inoperable HNSCC, N 40 mg every 6 weeks with TMC yields OS and PFS matching those of fortnightly nivolumab, of three-weekly pembrolizumab with chemotherapy, and of three-weekly N plus TMC, while requiring fewer hospital attendances, less expenditure and less disruption of the patient. Tolerability was acceptable, and the schedule was more affordable.