# Low-dose nivolumab with neoadjuvant chemotherapy and oral metronomic therapy in borderline resectable oral cavity squamous cell carcinoma: a phase II trial

## TL;DR

A new treatment combining low-dose immunotherapy with chemotherapy and oral drugs improves surgery success and outcomes in hard-to-treat mouth cancer.

## Contribution

A novel outpatient chemo-immunotherapy regimen (NeoLOCUS) is proposed for borderline resectable oral cavity squamous cell carcinoma.

## Key findings

- 90.3% surgical conversion rate achieved with the NeoLOCUS regimen.
- 41.4% of patients showed major pathological response, including four with complete response.
- Only 14.7% of patients experienced grade ≥3 toxicities, with no treatment-related deaths.

## Abstract

Non-surgical management of oral cavity squamous cell carcinoma (OSCC) has poorer outcomes compared to surgery. In borderline resectable tumors, historical neoadjuvant chemotherapy achieves surgical conversion in only about 40%. Combining low-dose immunotherapy and oral metronomic therapy (OMT) with chemotherapy may enhance resection rate and survival.

Between April 2023 and April 2024, patients deemed ‘borderline resectable’ OSCC based on predefined criteria by a multidisciplinary tumor board were prospectively offered this Phase II single-arm interventional trial setting. Patients received two 21-day cycles of carboplatin, nab-paclitaxel, low-dose nivolumab, and six weeks of erlotinib, methotrexate, celecoxib, with additional cycle(s) if needed. Primary endpoint was R0 resection rate. Secondary endpoints were objective response rate, pathologic response, safety, event-free survival (EFS), and overall survival (OS). Immune biomarkers and Volumetric assessment were exploratory endpoints. The trial was prospectively registered in the Clinical Trial Registry of India (CTRI/2023/04/051617).

Of 34 patients, all except one completed planned neoadjuvant therapy. After 2 cycles, 22 (66·6%) had partial response and 11 had stable disease; none progressed. Twenty six underwent surgery; 25 achieved R0 resection (25/33–75·7% conversion). Four of seven remaining patients received additional cycle(s); three subsequently achieved R0 resection. Overall conversion rate was 90·3% (28/31) excluding 2 patients who refused further treatment. Major pathological response occurred in 12 patients (41·4%), including four with pathological complete response. Grade ≥3 toxicities occurred in 5 of 34 patients (14·7%), with no treatment-related deaths. One patient had grade 4 diarrhea with grade 4 acute kidney injury.

The NeoLOCUS regimen offers an affordable, outpatient chemo-immunotherapy approach that improves surgical conversion and pathological response in borderline resectable OSCC.

Fluid Research Grant- 10.13039/501100005918Christian Medical College, Vellore, India.