Efficacy and safety of taxane platinum doublet chemotherapy with triple oral metronomic chemotherapy and low dose nivolumab as neoadjuvant therapy in locally advanced head and neck squamous cell carcinoma.

e18103 Background: In India, 80–90% of patients with head and neck squamous cell carcinoma (HNSCC) present with locally advanced disease. Randomized studies comparing neoadjuvant therapy (NACT) with the three-drug TPF regimen (taxane, platinum, and 5-FU) with the two-drug TP regimen (taxane and platinum) have shown improved downstaging and OS benefit with TPF. However, administering TPF in resource-limited settings is challenging. The combination of TP and triple-OMCT [oral metronomic chemotherapy consisting of methotrexate, celecoxib, and erlotinib] is easier to deliver and has a better tolerability profile. Despite this, the median overall survival (OS) remains between 1.0 to 1.5 years. In this study, we evaluated the addition of low-dose immunotherapy (IO) to the TP and triple-OMCT combination regimen in our patient cohort. Methods: This single-centre observational study (August 2023 to October 2024) evaluated patients with locally advanced HNSCC planned for NACT in the multi-disciplinary joint clinic. Eligible patients received weekly paclitaxel 80mg/m2, carboplatin AUC-2, triple-OMCT (tablet methotrexate 9mg/m2 weekly, tablet erlotinib 150mg once daily, capsule celecoxib 200mg twice daily), and 3-weekly low-dose nivolumab (20mg or 40mg). We assessed objective responses (ORR), safety, pathological responses [major (MPR) and complete (pCR) response], and survival outcomes [event-free survival (EFS) and OS] in our patients. Results: Data of 69 patients was analyzed. The median age was 49 years (IQR, 41-58), 87% were males, 85% chewed tobacco, and 98% had an ECOG-PS of 0-1. Oral cavity was the primary tumor site in 74% (n=51) patients. Clinical T3/T4 lesion was seen in 78% (n=54) patients, N2/N3 disease in 79% (n=55) patients, and stage IVA/B disease in 95% (n=66) patients. The baseline disease was resectable (recurrent disease), technically unresectable, and unresectable (or resection not routinely done) in 2.9% (n=2), 42% (n=29), and 55% (n=38) patients respectively. All patients completed the planned treatment, and the median number of chemotherapy and IO cycles were 8 (IQR, 7-9) and 3 (IQR, 3-4) respectively. Among response evaluable patients (n=63), the ORR was 65% (n=41 partial responses). > Grade 3 toxicities were seen in 46% (n=32) patients, and none had IO-related toxicities. At data cut-off, 51% (n=16/31) eligible patients underwent surgery. The pCR and MPR rate was 12.5% (n=2/16) and 50.0% (n=8/16) respectively. The median follow-up of the cohort was 7.0 months (95%CI, 6.0-7.9). The median EFS and OS was 12.9 months (95%CI, 8.2-17.6) and ‘Not Reached’ respectively. Conclusions: The combination of TP chemotherapy with triple-OMCT and low-dose nivolumab is a highly efficacious and safe neoadjuvant regimen. Longer follow-up is needed to assess its impact on survival outcomes.