Lower doses of checkpoint inhibitors may be an effective option for patients who cannot tolerate full doses, according to investigators who studied nivolumab in patients with advanced head and neck squamous cell carcinoma. “To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved overall survival and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors,” the authors conclude.
In a randomized phase 3 superiority study, 151 adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma were being treated with palliative intent. Randomization to triple metronomic chemotherapy (TMC) consisting of oral methotrexate, celecoxib, and erlotinib, or to TMC with intravenous nivolumab (TMC-I) showed these results based on a primary outcome of 1-year overall survival: “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).”
Editorial: “In many ways, the current state of cancer immunotherapy is analogous to that of HIV medications two decades ago,” editorialists write. “At that time, highly effective medications were available only in wealthy countries. In Africa, where disease prevalence was high, the drug prices were too high to be widely accessible, and patients continued to die as a result. Similarly, immunotherapy is highly effective for some cancers, yet it is out of reach for most patients in poor countries. With lower doses and lower costs, many deaths could be prevented. Perhaps ultra-low dosing of cancer drugs will provide the much-needed solution for these patients.”