Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study
| Autor: | Dirk Waldschmidt, J-B. Bachet, Lawrence Fong, J. Tabernero, Michele Reni, H-M. Chang, Sara Lonardi, G. Cole, Margaret A. Tempero, Andrew Eugene Hendifar, D-Y. Oh, L.C. Tsao, Teresa Macarulla, Danelle F. James, E. Van Cutsem, Juan Maurel, Lisa M. Coussens, Naureen Starling, Rocio Garcia-Carbonero |
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| Přispěvatelé: | Institut Català de la Salut, [Tempero M] Department of Medicine, University of California San Francisco, San Francisco, USA. [Oh DY] Department of Internal Medicine, Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. [Tabernero J, Macarulla T] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UICC, CIBERONC, Barcelona, Spain. [Reni M] Department of Radiochemotherapy, San Raffaele Hospital Scientific Institute, Milan, Italy. [Van Cutsem E] Department of Digestive Oncology, University Hospitals Gasthuisberg/Leuven & KU Leuven, Leuven, Belgium. [Hendifar A] Department of Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, USA, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology metastatic pancreatic adenocarcinoma Other subheadings::Other subheadings::/drug therapy [Other subheadings] Deoxycytidine Tyrosine-kinase inhibitor chemistry.chemical_compound 0302 clinical medicine Piperidines Antineoplastic Combined Chemotherapy Protocols Tumor Microenvironment neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES] terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Hematology 3. Good health Treatment Outcome 030220 oncology & carcinogenesis Ibrutinib medicine.drug medicine.medical_specialty Randomization Paclitaxel medicine.drug_class Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Adenocarcinoma Neutropenia Placebo Quimioteràpia combinada 03 medical and health sciences ibrutinib Albumins Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Internal medicine Pàncrees - Càncer - Tractament medicine Humans Adverse effect Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [DISEASES] business.industry Adenine diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] medicine.disease Gemcitabine phase III Discontinuation Pancreatic Neoplasms 030104 developmental biology chemistry Avaluació de resultats (Assistència sanitària) business |
| Zdroj: | Scientia |
| ISSN: | 0923-7534 |
| DOI: | 10.1016/j.annonc.2021.01.070 |
| Popis: | Ibrutinib; Metastatic pancreatic adenocarcinoma; Phase III Ibrutinib; Adenocarcinoma de páncreas metastásico; Fase III Ibrutinib; Adenocarcinoma de pàncrees metastàtic; Fase III First-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) includes nab-paclitaxel/gemcitabine. Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumor activity through tumor microenvironment modulation. The safety and efficacy of first-line ibrutinib plus nab-paclitaxel/gemcitabine treatment in patients with PDAC were evaluated. Patients and methods RESOLVE (NCT02436668) was a phase III, randomized, double-blind, placebo-controlled study. Patients (histologically-confirmed PDAC; stage IV diagnosis ≥6 weeks of randomization; Karnofsky performance score ≥70) were randomized to once-daily oral ibrutinib (560 mg) or placebo plus nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2). Primary endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS); overall response rate and safety were assessed. Results In total, 424 patients were randomized (ibrutinib arm, n = 211; placebo arm, n = 213). Baseline characteristics were balanced across arms. After a median follow-up of 25 months, there was no significant difference in OS between ibrutinib plus nab-paclitaxel/gemcitabine versus placebo plus nab-paclitaxel/gemcitabine (median of 9.7 versus 10.8 months; P = 0.3225). PFS was shorter for ibrutinib plus nab-paclitaxel/gemcitabine compared with placebo plus nab-paclitaxel/gemcitabine (median 5.3 versus 6.0 months; P < 0.0001). Overall response rates were 29% and 42%, respectively (P = 0.0058). Patients in the ibrutinib arm had less time on treatment and received lower cumulative doses for all agents compared with the placebo arm. The most common grade ≥3 adverse events for ibrutinib versus placebo arms included neutropenia (24% versus 35%), peripheral sensory neuropathy (17% versus 8%), and anemia (16% versus 17%). Primary reasons for any treatment discontinuation were disease progression and adverse events. Conclusions Ibrutinib plus nab-paclitaxel/gemcitabine did not improve OS or PFS for patients with PDAC. Safety was consistent with known profiles for these agents. This work was supported by Pharmacyclics LLC, an AbbVie Company (no grant number). |
| Databáze: | OpenAIRE |
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