Background

Head and neck cancer is a huge burden in South East Asia with frequent relapse after curative therapy, while the rest present in advanced unresectable stages. Financial constraints for targeted and immunotherapy make it inaccessible for the bulk of the population. Thus, a low-cost but efficacious regimen is highly implicated. We assessed if the readily available triplet therapy of EMF is superior in terms of extending life and maintaining quality of life, along with the evaluation of CTCs as a predictive biomarker in such patients.

Methods

This was a single-arm, phase II, investigator-initiated interventional study, wherein 35 patients were enrolled. Platinum-resistant/refractory patients of HNSCC were treated with a combination of erlotinib 150 mg daily, methotrexate 40 mg/m2, and 5-fluorouracil 500 mg/m2 (d1, d8) q28 days till progression or unacceptable toxicities. The primary endpoint was the overall response rate (ORR) at 3 months; additional endpoints were disease control rate (DCR) at 3 months, overall survival (OS), progression-free survival (PFS), safety, and patient-reported quality of life (QOL). The role of CTCs in gauging the responders and non-responders was monitored using anti-Epithelial Cell Adhesion Molecule antibody-based enrichment on the OncoDiscover Drug Controller General of India (DCGI) approved platform.

Results

The ORR and DCR at 3 months were 45.7% and 68.5%, respectively. The median PFS was 5 months (95% CI: 3.9-6 months) and median 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 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%) patients respectively. The grade 3 events seen were rash in 5 (14.2%) and diarrhea in 2 (5.7%). Clinically significant improvement was seen in domains of role functioning, social functioning, fatigue, pain and global health status, swallowing, dryness of mouth, and feeling ill. The mean CTC count at baseline was 0.90 ± 1.1 / 1.5 ml of blood.

Responders showed a decline in levels from 1.19 ± 0.25 to 0.33 ± 0.48, while non-responders had an increasing trend: 0.29 ± 0.48 to 1 ± 0.10 at 3 months (p = 0.010); with concordance rates with response being 52.9%. Additionally, CTC clearance at 3 months had a numerically better PFS of ~6 months (95% CI: 4.72-7.72) and OS of 10 months (95% CI: 2.3-5.65) vs 4 months (95% CI: 2.3-5.65), p = 0.258, and 8 months (95% CI: 4.3-11.6), p = 0.203 in those with persistence of CTCs.

Conclusions

The triplet regimen of EMF is a feasible, safe therapeutic option with favorable response rates and improved QOL in patients with platinum-resistant/refractory HNSCC. CTCs have a promising futuristic role as a predictive biomarker and can be extrapolated in the clinical upfront setting too.

Clinical Trial Information

CTRI/2020/02/023378.