Universität zu Köln

Tempero, M., Oh, D-Y, Tabernero, J., Reni, M., Van Cutsem, E., Hendifar, A., Waldschmidt, D-T, Starling, N., Bachet, J-B, Chang, H-M, Maurel, J., Garcia-Carbonero, R., Lonardi, S., Coussens, L. M., Fong, L., Tsao, L. C., Cole, G., Jr., James, D. and Macarulla, T. (2021). Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study. Ann. Oncol., 32 (5). S. 600 - 609. AMSTERDAM: ELSEVIER. ISSN 1569-8041

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Abstract

Background: 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/m(2)) and gemcitabine (1000 mg/m(2)). 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tempero, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oh, D-Y UNSPECIFIED UNSPECIFIED UNSPECIFIED Tabernero, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reni, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Cutsem, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hendifar, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldschmidt, D-T UNSPECIFIED UNSPECIFIED UNSPECIFIED Starling, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bachet, J-B UNSPECIFIED UNSPECIFIED UNSPECIFIED Chang, H-M UNSPECIFIED UNSPECIFIED UNSPECIFIED Maurel, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Carbonero, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lonardi, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Coussens, L. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fong, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsao, L. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, G., Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED James, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Macarulla, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-606111
DOI:	10.1016/j.annonc.2021.01.070
Journal or Publication Title:	Ann. Oncol.
Volume:	32
Number:	5
Page Range:	S. 600 - 609
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1569-8041
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER; IMPROVEMENTS; INHIBITOR; SURVIVAL; THERAPY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60611