A phase III randomized, open-label study to establish the superiority of triple oral metronomic therapy (OMCT) used in addition to chemotherapy regimen (paclitaxel + carboplatin) over chemotherapy alone for the treatment of advanced unresectable head and neck cancer squamous cell cancer (HNSCC).
Authors: Akhil Kapoor, Anuj Gupta, Bipinesh Sansar, Bal Krishna Mishra, Pooja Gupta, Arpita Singh, Ankita Rungta Kapoor, Sambit Swarup Nanda, Ashutosh Mukherji, Rukmeena Kumari, Ankita Pal, Satyendra Narayan Singh, Aseem Mishra, Ipsita Dhal, Kunal Ranjan Vinayak, Somnath Dey, Vanita Noronha, Vijay Maruti Patil, Shripad Dinanath Banavali, Kumar Prabhash
Journal: Journal of Clinical Oncology (2024)

LBA6053 Background: Advanced HNSCC has poor outcomes and limited treatment options, especially in resource-constrained settings. Immunotherapy is affordable for less than 5% of patients in lower-middle-income countries (LMICs). Triple OMCT, employing low-dose continuous chemotherapy, shows promise, but its safety and efficacy along with chemotherapy remain unproven. We aimed to assess whether the addition of OMCT to first-line chemotherapy can improve overall survival (OS) as compared to chemotherapy alone. Methods: This phase 3 randomized, prospective, open-label, superiority design study enrolled patients with advanced HNSCC who were planned for palliative intent platinum-based chemotherapy. The patients were stratified for the site of the tumor and ECOG PS, and were randomly assigned 1:1 to receive either triple OMCT (Erlotinib 150 mg OD, Celecoxib 200 mg BD and Methotrexate 9mg/m 2 once weekly) in addition to 3-weekly paclitaxel carboplatin (PC) chemotherapy (Arm A) or, PC chemotherapy alone (Arm B). Sample size calculation assumed no OS improvement with OMCT+PC (5% type I error, 80% type II error). The primary endpoint was OS, while secondary endpoints included PFS, quality of life (QoL) assessments, and safety. OS and PFS were analyzed via Kaplan-Meier and log-rank test; HR estimated via Cox proportional hazard models. QoL was assessed using EORTC QLQ-C30. The study was approved by Institutional Ethics Committee and registered with the Clinical Trials Registry India (CTRI/2022/10/046520). Results: Between Nov 02, 2022, and Dec 20, 2023, 238 patients were randomly assigned with 119 in each arm. Median age was 47 years, with 97.8% being males, and 78% of patients had ECOG PS 0-1. The median OS for patients in Arm A was 8.3 months (95% CI, 6.3-10.4) while it was 6.1 months (95% CI, 4.7-7.4), in Arm B (HR 0.63; 95% CI, 0.47–0.83; p=0.00011). The corresponding median PFS was 7.6 months (95% CI, 6.3-8.8) and 3.5 months (95% CI, 2.2-4.7) (HR, 2.79; 95% CI, 1.98-3.93; P&lt;0.000). Significant differences in EORTC-C30 were found for the physical functioning domain between baseline and 1-month follow-up visit. PC chemotherapy combined with triple OMCT showed good tolerability, with common toxicities including fatigue (40.3%), and hyponatremia (25.4%), similar to the incidence observed with PC chemotherapy alone. Conclusions: This study demonstrates that the addition of triple OMCT to paclitaxel and carboplatin chemotherapy is an effective and safe treatment option for patients with advanced HNSCC in platinum-sensitive settings. This treatment option is particularly valuable in LMICs, where cetuximab and pembrolizumab are not feasible. Clinical trial information: CTRI/2022/10/046520 . [Table: see text]