Neoadjuvant Chemotherapy Could Enhance Organ Preservation in Nasal and Paranasal Sinus Squamous Cell Carcinoma

Neoadjuvant chemotherapy prior to surgery and post-operative radiation therapy (PORT) could improve organ preservation in patients with T3 and T4a nasal and paranasal sinus squamous cell carcinoma (NPNSCC), according to data from the phase 2 EA3163 trial (NCT03493425) presented at the 2024 ESMO Congress.

Findings showed that among the population of patients with T3 or T4a disease and excluding those with clinical T4b disease (n = 18), the structural preservation (SP) rate was 33%. Patients treated in the neoadjuvant chemotherapy arm (n = 7) achieved an SP rate of 57% (95% CI, 18.4%-90.1%) compared with 18% (95% CI, 2.3%-51.8%) for those who proceeded directly to surgery (n = 11). However, the difference was not statistically significant (P = .14).

In the population of patients with T3 or T4a disease and excluding those with pathological T4b disease (n = 18), the overall SP rate was 39%. The SP rates for the neoadjuvant chemotherapy (n = 7) and control (n = 11) arms were 71% (95% CI, 29.0%-96.3%) and 18% (95% CI, 2.3%-51.8%), respectively; this difference was statistically significant (P = .049).

Among all treated patients, including those with T4b disease (n = 23), the SP rate was 30%. The respective SP rates for the neoadjuvant chemotherapy (n = 10) and control (n = 13) arms were 50% (95% CI, 18.7%-81.3%) and 15% (95% CI, 1.9%-45.4%); the difference was not statistically significant (P = .17).

“Despite the challenges in enrollment and an underpowered study, it is clear to us that there was a noted, improved SP with neoadjuvant chemotherapy, or at least a trend in that direction. That is most apparent for patients with notable resectable disease [T3 or T4a]. Patients with T4b disease enrolled on this trial were also deemed resectable, but they were carefully selected for resectability,” lead study author Nabil Saba, MD, of the Winship Cancer Institute of Emory University in Atlanta, Georgia, said during the presentation.

The proximity of NPNSCC to the orbit, base of the skull, and central nervous system has been associated with difficulties in the treatment of this patient population, Saba explained during the presentation, noting that resection of the orbit or base of skull can lead to increased morbidity and mortality.

The lack of prospective data has limited the potential role of neoadjuvant chemotherapy in the treatment of this patient population, and EA3163 sought to evaluate the role of preoperative treatment on organ preservation for those with NPNSCC deemed in need of sacrificing the orbit or base of skull.

Study Design

EA3163 was a phase 2, prospective, randomized, multicenter trial that enrolled patients with stage T3, T4a, and select T4b NPNSCC with N0 or N1 to N3 disease who required resection of the skull base, orbit, or both.

Patients were randomly assigned to receive surgery alone followed by PORT with or without cisplatin at 40 mg/m²; or neoadjuvant chemotherapy consisting of 3 cycles of docetaxel at 75 mg/m² plus cisplatin at 75 mg/m² or 3 cycles of docetaxel plus carboplatin at area under the curve 5, followed by surgery and PORT with or without cisplatin.

The coprimary objectives of the study were SP rate, defined as the successful preservation of both the skull base and orbit, and overall survival (OS).

The study hypothesized that neoadjuvant chemotherapy would increase the SP preservation rate from 2% in the control arm to 18% in the neoadjuvant chemotherapy arm and reduce the hazard of death by 42% compared with surgery alone with a 2-year OS rate of 50% vs 30%.

Notably, after initiating enrollment on March 28, 2018, enrollment was closed on November 7, 2023, due to slow accrual.

Baseline Patient Characteristics

Among the 29 patients enrolled, 3 were deemed ineligible due to unknown M stage (n = 1), poor kidney function (n = 1), and lack of orbit and/or base of skull involvement (n = 1). One additional patient withdrew prior to the start of therapy, and 2 patients did not proceed to surgery.

In the overall population of 25 patients, the median age was 63.4 years (range, 46.1-86.6). The majority were male (64%), had stage T4a disease (56%), and had N0 disease (64%). Regarding primary disease site, the most common locations were the maxillary sinus (56%) nasal cavity (36%), ethmoid sinus (4%), and both nasal cavity and ethmoid sinus (4%).

Ninety-one percent of evaluable patients (n = 23) had base of skull involvement at baseline, and 61% had orbital involvement. Both base of skull and orbital involvement were reported in 52% of patients.

Additional Efficacy Findings

The overall orbit preservation rate among all evaluable patients, including those with T4b disease (n = 23), was 57%. The orbital preservation rate was 70% (95% CI, 34.8%-93.3%) in the neoadjuvant chemotherapy arm vs 46% (95% CI, 19.2%-74.9%) in the control arm. The base of skull preservation rate was 52% in all patients; the respective rates were 70% (95% CI, 34.8%-93.3%) and 38% (95% CI, 13.9%-68.4%) in the neoadjuvant chemotherapy and surgery alone arms

Excluding patients with T4b disease, the overall 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. These rates were both 45% (95% CI, 16.7%-76.6%) in the control arm.

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.

Reference

Saba NF, Flamand Y, Lin DT, et al. Phase II randomized trial of neo-adjuvant chemotherapy followed by surgery and post-operative radiation versus surgery and post-operative radiation for organ preservation of T3 and T4a (selected T4b) nasal and paranasal sinus squamous cell carcinoma (NPNSCC): a trial of the ECOG-ACRIN Cancer Research Group (EA3163). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 850MO.