A single-arm feasibility phase II study of EMF (erlotinib + methotrexate + 5-fluorouracil) regimen in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is a huge burden in India with the majority of patients presenting in advanced unresectable stages. Innovative, low-cost but efficacious regimens that can be easily administered in the outpatient setting are the need of the hour. We envisaged assessing whether a readily available triplet therapy of erlotinib + methotrexate + 5-fluorouracil (EMF) is efficacious in terms of extending life and maintaining the quality of life in such patients.

PATIENTS AND METHODS

This was a single-arm, phase II, investigator-initiated interventional study. Thirty-five platinum-resistant/refractory patients of HNSCC were treated with a combination of erlotinib 150 mg, methotrexate 40 mg/m2 (d1, d8) and 5-fluorouracil 500 mg/m2 (d1, d8) every 28 days till progression or unacceptable toxicities. The primary endpoint was overall response rates (ORRs) at 3 months; additional endpoints were disease control rate (DCR) at 3 months, overall survival (OS) and progression-free survival (PFS), safety and patient-reported quality of life.

RESULTS

The ORR and DCR at 3 months were 45.7% and 68.5%, respectively. The PFS was 5 months (95% confidence interval (95% CI): 3.9-6 months) and the OS was 9 months (95% CI: 7.4-10.5 months). The 3- and 6-month PFS rates were 86% ± 6% and 45% ± 9%, respectively, while the OS rates at 3 and 6 months were 91% ± 5% and 68% ± 8%, respectively. Rash, mucositis and fatigue were common adverse events occurring in 23 (65%), 14 (40%) and 9 (25.7%), respectively. The most common grade 3 events seen were rash in 5 (14.2%) and diarrhoea in 2 (5.7%). Clinically significant improvement from baseline was seen in many domains of Quality of Life Core Questionnaire and Quality of Life Head and Neck Module.

CONCLUSIONS

The triplet regimen of EMF is a feasible and safe therapeutic option in patients with platinum-resistant/refractory HNSCC. It has demonstrated favourable response rates and improvement in quality of life; however, a randomised phase III study would add more robust value (NCT: CTRI/2020/02/023378).