Nab-paclitaxel plus bevacizumab for patients with metastatic extrapulmonary neuroendocrine carcinoma: a phase 2 single-arm study.

Abstract

Patients with advanced extrapulmonary neuroendocrine carcinoma (EP-NEC) usually present with metastatic disease and have a poor prognosis. No standard therapies have been established beyond the first-line platinum-based chemotherapy. This study aims to evaluate the efficacy and safety of nab-paclitaxel plus bevacizumab in patients with previously treated advanced EP-NEC. This multicenter, single-arm, phase 2 trial was conducted from January 2021 to March 2024 to evaluate the efficacy and safety of nab-paclitaxel plus bevacizumab in patients with advanced EP-NEC who progressed after prior standard-of-care treatments. Patients were assigned to receive nab-paclitaxel of 150 mg/m² plus bevacizumab of 5 mg/kg intravenously every 2 weeks in a cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall survival (OS). The secondary endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and safety. The study was registered at ClinicalTrials.gov: NCT04705519 (https://clinicaltrials.gov/study/NCT04705519?cond=NCT4705519&rank=1). A total of 79 patients were enrolled, with 40 patients receiving ≥2 lines of therapy. After a median follow-up of 22.4 (Interquartile Range [IQR] 14.7-42.9) months, the median OS was 12.8 (95% CI, 8.6-17.4) months. The median PFS was 5.3 (95% CI, 4.2-6.6) months. Among 76 patients with assessable best response, the ORR was 55% (42/76, 95% CI 43-67%), and DCR was 87% (66/76, 95% CI 77-94). The median DoR was 5.7 (95% CI, 3.3-7.2) months. Patients with gastric NEC had a numerically higher ORR compared with those with NEC from other sites, but statistical significance was not achieved (26/39, [67%] vs. 16/37, [43%]; <i>P</i> = 0.068); however, no statistically significant difference in PFS (6.6 [95% CI 3.9-7.5] vs. 4.6 [95% CI 2.6-6.3]; <i>P</i> = 0.13) or OS (14.4 [95% CI 7.7-18.4] vs. 10.0 [95% CI 7.2-20.0]; <i>P</i> = 0.76) was observed. Multivariable analyses identified that metastatic organs >2 was the independent factor significantly associated with worse PFS (HR 2.06, 95% CI 1.20-3.56; <i>P</i> = 0.0092) and OS (HR 1.86, 95% CI 1.04-3.30; <i>P</i> = 0.035). Most treatment-related adverse events (TRAEs) (≥10%) of grade ≥3 were neutropenia (28/79, 35%) and leukopenia (15/79, 19%). Patients with metastatic EP-NEC achieved a high response rate and encouraging survival with tolerable toxicity. The combination regimen has the potential to become a valuable treatment option, if further controlled studies confirm its efficacy for patients who have exhausted standard therapies. This study was partially supported by Qilu Pharmaceutical Co., Ltd. This work is supported by the Beijing Municipal Science & Technology Commission (No. Z231100007223002).