Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study.
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Embargo End Date
ICR Authors
Authors
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, LM
Fong, L
Tsao, LC
Cole, G
James, D
Macarulla, T
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, LM
Fong, L
Tsao, LC
Cole, G
James, D
Macarulla, T
Document Type
Journal Article
Date
Date Accepted
2021-01-20
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.
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2021, 32 (5), pp. 600 - 608
Source Title
Publisher
ISSN
0923-7534
eISSN
1569-8041
Collections
Research Team
Gastrointestinal Cancers Clinical Trials
Gastrointestinal Cancers Clinical Trials
Gastrointestinal Cancers Clinical Trials