Neoadjuvant chemotherapy followed by postoperative radiation therapy (PORT) demonstrates potential benefits for organ preservation in patients with T3 and T4a nasal and paranasal sinus squamous cell carcinoma (NPNSCC), according to the phase 2 EA3163 trial (NCT03493425) presented at the 2024 ESMO Congress. The study, while underpowered due to slow accrual, suggests a trend towards improved structural preservation (SP) with neoadjuvant chemotherapy.
Structural Preservation Outcomes
In patients with T3 or T4a disease (n = 18), the structural preservation (SP) rate was 33%. Specifically, the neoadjuvant chemotherapy arm (n = 7) achieved an SP rate of 57% (95% CI, 18.4%-90.1%) compared to 18% (95% CI, 2.3%-51.8%) for those undergoing immediate surgery (n = 11). While the difference indicated a potential benefit, it did not reach statistical significance (P = .14).
Considering all treated patients, including those with T4b disease (n = 23), the SP rate was 30%. The neoadjuvant chemotherapy arm (n = 10) showed an SP rate of 50% (95% CI, 18.7%-81.3%) versus 15% (95% CI, 1.9%-45.4%) in the control arm. This difference also was not statistically significant (P = .17).
Investigator Insights
According to lead study author Dr. Nabil Saba, MD, of the Winship Cancer Institute of Emory University, the study suggests a notable trend towards improved SP with neoadjuvant chemotherapy, particularly in patients with resectable T3 or T4a disease. He noted that while patients with T4b disease were enrolled, they were carefully selected for resectability.
Study Design and Objectives
The EA3163 trial was a phase 2, prospective, randomized, multicenter study involving patients with stage T3, T4a, and select T4b NPNSCC with N0 or N1 to N3 disease requiring resection of the skull base, orbit, or both. Participants were randomized to either surgery followed by PORT with or without cisplatin or neoadjuvant chemotherapy (3 cycles of docetaxel plus cisplatin or docetaxel plus carboplatin) followed by surgery and PORT with or without cisplatin.
The primary objectives were SP rate, defined as successful preservation of both the skull base and orbit, and overall survival (OS). The study aimed to determine if neoadjuvant chemotherapy could increase the SP rate from 2% in the control arm to 18% and reduce the hazard of death by 42%, with a 2-year OS rate of 50% vs 30%.
Enrollment, initiated on March 28, 2018, was closed on November 7, 2023, due to slow accrual.
Patient Characteristics
The study enrolled 29 patients, with 25 being evaluable. The median age was 63.4 years (range, 46.1-86.6), with the majority being male (64%), having stage T4a disease (56%), and N0 disease (64%). The most common primary disease sites were the maxillary sinus (56%) and nasal cavity (36%). Ninety-one percent had base of skull involvement, and 61% had orbital involvement; 52% had both.
Orbit and Skull Base Preservation
Among all evaluable patients, the overall orbit preservation rate was 57%. The rate was 70% (95% CI, 34.8%-93.3%) in the neoadjuvant chemotherapy arm versus 46% (95% CI, 19.2%-74.9%) in the control arm. The base of skull preservation rate was 52% overall, with rates of 70% (95% CI, 34.8%-93.3%) and 38% (95% CI, 13.9%-68.4%) in the neoadjuvant chemotherapy and surgery alone arms, respectively.
Excluding patients with T4b disease, orbital and base of skull preservation rates were 56% and 61%, respectively. In the neoadjuvant chemotherapy arm, the orbital and base of skull preservation rates for those with T3 or T4a disease were 71% (95% CI, 29.0%-96.3%) and 86% (95% CI, 42.1%-99.6%), respectively, compared to 45% (95% CI, 16.7%-76.6%) in the control arm for both.
Overall Survival
OS data from the EA3163 trial remained immature. The estimated 2-year OS rates were 90.9% (95% CI, 50.8%-98.7%) in the standard arm and 90.0% (95% CI, 47.3%-98.5%) in the neoadjuvant chemotherapy arm.
