850MO - Phase II randomized trial of chemotherapy followed by surgery and PORT versus surgery and PORT for organ preservation of T3 and T4a (selected T4b) sinonasal squamous cell carcinoma (SNC): A trial of the ECOG-ACRIN cancer research group (EA3163)

Background

The standard of care for T3 and T4a SNC is surgery with possible sacrifice of structures including orbit and base of skull. Neoadjuvant chemotherapy for structure preservation (SP) has not been tested in a randomized trial. EA3163 is a randomized study investigating whether cyto-reductive pre-operative chemotherapy would improve SP rate or benefit overall survival. We report here the SP analysis.

Methods

Patients with T3, T4a, and selected T4b resectable NPNSCC requiring orbital or skull base resection were randomized to surgery followed by PORT of 60 Gy versus the same treatment preceded by neoadjuvant docetaxel 75mg/m² and cisplatin 75 mg/m² X 3 cycles. Degree of anticipated SP (orbit and skull base) was required pre, post chemotherapy and at surgery. Co-primary objectives were SP rate and overall survival (OS). Eighty-two patients needed to be accrued (full information at 65 events) with a power of 81% with 0.1 one-sided alpha using Fisher’s exact test for SP and 83% with 0.1 one-sided alpha using Log rank test for OS.

Results

The study was activated in March 2018, and closed due to slow accrual in November 2023, after enrolling 29 patients. Four patients were ineligible, 2 patients did not proceed to surgery, and 1 patient is pending blinded review of SP data. Among 22 evaluable patients, the overall SP rate is 32% (N=7/22), with 15% (N=2/13, 95% exact binomial CI: 1.9%, 45.4%) in the standard arm and 56% (N=5/9, 95% exact binomial CI: 21.2%, 86.3%) in the experimental arm (p=0.07). The overall orbit preservation rate is 55% (N=12/22), 46% in the standard arm (N=6/13, 95% exact binomial CI: 19.2%, 74.9%) and 67% in the experimental arm (N=6/9, 95% exact binomial CI: 29.9%, 92.5%). The overall skull base preservation rate is 55% (N=12/22), 38% in the standard arm (N=5/13, 95% exact binomial CI: 13.9%, 68.4%) and 78% in the experimental arm (N=7/9, 95% exact binomial CI: 40.0%, 97.2%).

Conclusions

Results from EA3163 suggest an improved SP with neo-adjuvant platinum-based chemotherapy in patients with resectable NPNSCC requiring orbit or skull base resection. The median OS has not been reached.

Clinical trial identification

NCT03493425.

Editorial acknowledgement

Legal entity responsible for the study

ECOG-ACRIN Cancer Research Group.

Funding

ECOG-ACRIN Cancer Research Group.

Disclosure

All authors have declared no conflicts of interest.