A real-world study of the effectiveness and safety of low-dose immunotherapy in addition to oral metronomic chemotherapy in recurrent and metastatic head and neck squamous cell carcinoma

The standard of care in recurrent/metastatic head and neck squamous cell carcinoma is Pembrolizumab with/without chemotherapy. However, these regimens are minimally affordable and accessible in resource-limited countries. Hence, immunotherapy is combined with oral metronomic chemotherapy in lower doses. Currently, the efficacy and safety of this regimen have been studied in platinum-refractory settings and not beyond them. Thus, we conducted a real-world study on the effectiveness of low-dose immunotherapy and metronomic chemotherapy in recurrent/metastatic head and neck cancer. This was a multicentre, real-world, prospective observational study. Recurrent/metastatic head and neck squamous cell carcinoma patients treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0–2 were recruited from three oncology centres. Patients received oral metronomic chemotherapy with IV nivolumab 20 mg once every 3 weeks. Patients received treatment until disease progression or unacceptable toxicities. The primary endpoints were Objective response rate, progression-free survival, and Overall survival. The secondary endpoint was safety. Moreover, subgroup analysis was also carried out among platinum sensitivity and the line of treatment. Overall, 123 patients were recruited (86% males and 35% females). The Objective response rate was 61.7% (95% CI, 53 to 70). The median overall survival and progression-free survival were 15.1 months (95% CI, 12.8–17.4) and 10.4 months (95% CI, 8.0-13.7), respectively. Moreover, the median overall survival was 15.9 (95% CI, 12.7 to 17.5) versus 8.0 months (95% CI, 3.4–12.6) (p < 0.01) and the median progression-free survival were 13.6 months (95% CI, 9.9–17.2) versus 5.0 months (95% CI, 2.2–7.8) (p < 0.01) for platinum sensitive and resistant subgroups respectively. The median OS were 15.1 months (95% CI, 12.7–17.5) versus 8.0 months (3.4–12.6) (p = 0.03), and the median PFS were 11.2 months (95% CI, 6.3–16.0) versus 6.0 months (95% CI, 2.7–9.3) (p = 0.07) for first and second-line subgroups, respectively. The most common adverse events were fatigue (63.4%), anemia (52.8%), mucositis (47.9%), and rashes (44.7%). This study demonstrated that adding low-dose immunotherapy to oral metronomic chemotherapy was effectively applicable and associated with manageable toxicities in a real-world setting for the management of R/M HNSCC. Furthermore, this regimen was associated with favourable survival outcomes and response rates in the platinum-sensitive and first-line treatment subgroups.