Neoadjuvant Chemotherapy Shows Promise in Nasal and Paranasal Sinus Cancer

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 (搜索)搜索该疾病 (NPNSCC), according to the phase 2 EA3163 trial (NCT03493425查看临床试验) 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查看药品详情 or neoadjuvant chemotherapy (3 cycles of docetaxel查看药品详情 plus cisplatin or docetaxel plus carboplatin查看药品详情) 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.