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Phase Ib/II study of ibrutinib (ibr) in combination with cetuximab (cetux) in patients (pts) with previously treated metastatic colorectal cancer (mCRC)
Oh, D. Y. Arkenau, T. Lee, K. W. Alsina, M. Marti-Marti, Francisca Chung, I. J. Saif, W. Wang, D. O'Dwyer, P. Chau, I.
Oh, D. Y.
Arkenau, T.
Lee, K. W.
Alsina, M.
Marti-Marti, Francisca
Chung, I. J.
Saif, W.
Wang, D.
O'Dwyer, P.
Chau, I.
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Abstract
Background: Third- or later-line treatments for mCRC have low response rates (1e
37%) and limited PFS (1.4e5.6 mo) and OS (6.1e14.0 mo) (Arnold Ann Oncol 2018).
Ibr is a once-daily Bruton’s tyrosine kinase (BTK) inhibitor approved for the treatment
of various B-cell malignancies. Ibr also inhibits other kinases, including ETK, ITK, and
EGFR tyrosine kinase (Wang Clin Cancer Res 2018; Dubovsky Blood 2013; Gao J Natl
Cancer Inst 2014), and may provide complementary activity with cetux. Dual targeting
of EGFR may improve OS in mCRC (Weickhardt J Clin Oncol 2012). This cohort of the
phase Ib/II study (NCT02599324) evaluated efficacy and safety of ibr + cetux in pts
with mCRC.
Methods: Eligible pts had KRAS or NRAS wild type mCRC previously treated with 2e4
regimens and were cetux-naive. Pts received oral ibr once daily at 560 mg (starting
dose) or 840 mg (recommended phase II dose) plus IV cetux (400 mg/m2 initial dosethen 250 mg/m2 weekly) in 21-d cycles until unacceptable toxicity or progression.
Efficacy (overall response rate [ORR], PFS, duration of response [DOR], disease control
rate [DCR], and OS) and safety are reported.
Results: 58 pts received ibr + cetux (ibr 560 mg, n¼8; ibr 840 mg, n¼50). Median age
was 62 y; 38%, 40%, and 22% of pts had received 2, 3, and 4 prior regimens for mCRC,
respectively. Median follow-up was 20.9 mo. ORR was 16% (Table). Median PFS was
4.8 mo (range 3.9e5.6). Median treatment duration was 3.2 mo for ibr and 3.0 mo for
cetux. Grade 3 adverse events (AEs) occurred in 41 pts (71%); the only grade 3 AE
occurring in 10% of pts was dermatitis acneiform (15 pts [26%]). Two pts (3%) had
AEs leading to death; neither were related to study drug. Two pts (3%) had major
hemorrhage and 53 pts (91%) had rash of any grade (grade 3 in 17 pts [29%]).
Conclusions: Ibr + cetux was moderately active in heavily pretreated, refractory,
cetux-naive pts with mCRC. There were no new safety signals and the safety profile
was consistent with those of the individual drugs.
Description
Date
2020
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Oh DY, Arkenau T, Lee KW, Alsina M, Marti FM, Chung IJ, et al. 439P Phase Ib/II study of ibrutinib (ibr) in combination with cetuximab (cetux) in patients (pts) with previously treated metastatic colorectal cancer (mCRC). Annals of Oncology. 2020;31:S428-S.