Nature communications · 2026
Cabozantinib and temozolomide in patients with advanced progressive neuroendocrine tumors: a phase 2 study.
СтатьяКлиническое исследование II фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Cives Mauro, Della Vittoria Scarpati Giuseppina, Clemente Ottavia, Lauricella Eleonora, Bracigliano Alessandra, Badalamenti Giuseppe, Delrio Paolo, Cannella Lucia, Picone Carmine, Ragno Anna, Chaoul Nada, Della Monica Rosa, Di Mauro Annabella, Pizzolorusso Antonio, Sorino Joana, Buonaiuto Michela, Ingravallo Giuseppe, Picozzi Fernanda, Pignataro Pasquale, Ferrara Gerardo, Porta Camillo, Tafuto Salvatore
Аннотация
Treatment options for patients with advanced neuroendocrine tumors (NETs) are limited. Preclinical and early clinical evidence suggest that cabozantinib and temozolomide may exert synergistic antitumor activity. We performed an open-label, single-arm, phase 2 study (NCT04893785) to assess the safety and efficacy of cabozantinib and metronomic temozolomide in patients with advanced, progressive, well-differentiated NETs of gastroenteropancreatic, pulmonary or unknown origin. Patients received cabozantinib 40 mg daily and temozolomide 100 mg/m2/day one week on/one week off. The primary endpoint was overall response rate (ORR) by blinded local review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), duration of response (DOR) and safety. Of the 37 patients enrolled, 14 harbored gastrointestinal NETs, 12 pancreatic NETs, 9 lung NETs and 2 NETs of unknown primary. Neoplasms were classified as G1, G2 or G3 in 9, 24 and 4 cases respectively. While all enrolled patients were assessable for toxicity, 33 met the criteria for per protocol assessment of efficacy. The ORR was 15% (95% CI, 5-31%) and did not meet the primary endpoint. However, after a median follow-up of 19.2 months, the CBR was 100% (95% CI, 89.5-100%) and the median PFS was 28.5 months (95% CI, 16.8-28.5 months). The median OS was not reached, with a 3-year OS rate of 68.5% ( ± 9.1%). The median DOR was 19.5 months. Lymphopenia (16%), thrombocytopenia (11%), diarrhea (8%) and colitis (8%) emerged as the most frequent grade ≥3 treatment-related adverse events. No treatment-related deaths were recorded. Deficiency of O⁶-methylguanine-DNA methyltransferase (MGMT) and c-MET expression were associated with response. The proportion of the patients benefitting of the treatment and its safety profile justify larger, controlled studies to further investigate the added role of combining cabozantinib with metronomic temozolomide. ClinicalTrials.gov identifier: NCT04893785.