Napabucasin plus nab-paclitaxel with gemcitabine versus nab-paclitaxel with gemcitabine in previously untreated metastatic pancreatic adenocarcinoma: an adaptive multicentre, randomised, open-label, phase 3, superiority trial
| Autor: | Tanios Bekaii-Saab, Takuji Okusaka, David Goldstein, Do-Youn Oh, Makoto Ueno, Tatsuya Ioka, Weijia Fang, Eric C. Anderson, Marcus S. Noel, Michele Reni, Hye Jin Choi, Jonathan S. Goldberg, Sang Cheul Oh, Chung-Pin Li, Josep Tabernero, Jian Li, Emma Foos, Cindy Oh, Eric Van Cutsem |
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| Přispěvatelé: | Institut Català de la Salut, [Bekaii-Saab T] Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA. [Okusaka T] Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. [Goldstein D] Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW, Australia. [Oh DY] Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea. [Ueno M] Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Kanagawa, Japan. [Ioka T] Oncology Center, Yamaguchi University Hospital, Yamaguchi, Japan. [Tabernero J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [DISEASES]
Otros calificadores::/uso terapéutico [Otros calificadores] Metastatic pancreatic adenocarcinoma terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Medicaments antineoplàstics - Ús terapèutic Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] General Medicine Pancreatic cancer Adenocarcinoma Other subheadings::Other subheadings::/drug therapy [Other subheadings] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Phosphorylated signal transducer and activator of transcription 3 Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Pàncrees - Càncer - Tractament Avaluació de resultats (Assistència sanitària) Other subheadings::/therapeutic use [Other subheadings] neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES] Napabucasin |
| Zdroj: | Scientia |
| Popis: | Adenocarcinoma; Napabucasin; Pancreatic cancer Adenocarcinoma; Napabucasin; Càncer de pàncrees Adenocarcinoma; Napabucasin; Cáncer de páncreas Background Compared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1. Methods In the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive). Findings Between 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5–12.2) and 11.7 (10.7–12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93–1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%). Interpretation Our findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC. This study was supported by Sumitomo Pharma Oncology, Inc. |
| Databáze: | OpenAIRE |
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