Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer
| Autor: | Larry Lyons, Martin Guiterrez, Aparna Kaylan, Sibabrata Banerjee, Rafia Bhore, Teng Jin Ong, David M. Waterhouse, Chrystal U. Louis, Daniel W. Pierce, Ben George, Rishi Jain, Edward J. Kim, Hatem Soliman, Daniel R. Carrizosa, Thomas Lila, David J. Reiss, Zev A. Wainberg, Aparna Raj Parikh, Peter J. O'Dwyer, E. Gabriela Chiorean, Howard S. Hochster |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Hepatitis Cancer Research medicine.medical_specialty business.industry medicine.disease Gastroenterology Confidence interval Gemcitabine Discontinuation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Respiratory failure 030220 oncology & carcinogenesis Internal medicine Pancreatic cancer Medicine Nivolumab business Adverse effect medicine.drug |
| Zdroj: | Clinical Cancer Research. 26:4814-4822 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-20-0099 |
| Popis: | Purpose: Assess safety and efficacy of nivolumab plus nab-paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial. Patients and Methods: Fifty chemotherapy-naive patients received nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2). Secondary efficacy endpoints were progression-free survival (PFS), overall survival (OS), and response. Assessment of programmed cell death-ligand 1 (PD-L1) expression was an exploratory endpoint; additional biomarkers were assessed post hoc. Results: One DLT (hepatitis) was reported in part 1 among six DLT-evaluable patients; 48 of 50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median [95% confidence interval (CI)] PFS/OS was 5.5 (3.25–7.20 months)/9.9 (6.74–12.16 months) months, respectively [median follow-up for OS, 13.6 months (95% CI, 12.06–23.49 months)]. Overall response rate (95% CI) was 18% (8.6%–31.4%). Median PFS/OS was 5.5/9.7 months (PD-L1 Conclusions: The safety profile of nivolumab plus nab-paclitaxel and gemcitabine at standard doses in advanced pancreatic cancer was manageable, with no unexpected safety signals. Overall, the clinical results of this study do not support further investigation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|