936P - Triple oral metronomic chemotherapy (OMCT) versus physician choice chemotherapy after failure of platinum-based therapy in advanced head and neck squamous cell cancer (HNSCC): A phase III randomized open-label study

Background

Advanced HNSCC patients with platinum-refractory disease have limited treatment options and poor outcomes, especially in resource-constrained settings. Triple metronomic therapy, a low-dose continuous chemotherapeutic strategy, has shown promise in phase 2 trials but requires further validation. We aimed to evaluate triple OMCT's efficacy in improving overall survival (OS) compared to physician-choice chemotherapy (PCC).

Methods

In this phase 3 open-label study, 214 advanced HNSCC patients previously treated with platinum-based chemotherapy (October 2021-August 2022) were randomized 1:1 to receive triple OMCT (Arm A) with Methotrexate 9 mg/m² PO weekly, Celecoxib 200 mg twice daily and erlotinib 150 mg daily, or PCC (Arm B), stratified by age and performance status. Primary endpoint was OS, with secondary endpoints including progression-free survival (PFS), Quality of Life (QoL) assessments, and safety. OS and PFS were analyzed using Kaplan-Meier and log-rank tests, with hazard ratios estimated by Cox proportional hazard models. QoL was assessed using EORTC QLQ-C30.

Results

Table: 936P

Baseline characteristics of the patients

Most patients had ECOG PS 1 (60.7%) and tumor site in the oral cavity (65.9%). With a median follow-up of 11 months, the median OS was 9 months in Arm A and 5 months in Arm B (HR, 0.63; 95% CI, 0.47–0.83; p=0.00011). Median PFS was 4 months in Arm A and 2 months in Arm B (HR, 0.67; 95% CI, 0.52–0.87; p<0.0001). Multivariate analysis identified age, hemoglobin level, and comorbidity as significant OS prognostic factors. No significant QoL score differences were observed. Triple OMCT showed fewer grade 3 or higher adverse events than PCC (28.0% vs 39.3%, p=0.03).

Conclusions

Triple OMCT is an effective, safe treatment for advanced HNSCC patients previously treated with platinum-based chemotherapy, offering improved OS and tolerable side effects compared to physician-choice chemotherapy.

Clinical trial identification

Clinical Trial Registry-India CTRI/2021/09/036296.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Indian Cooperative Oncology Network (ICON) Trust.

Disclosure

All authors have declared no conflicts of interest.