In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 7523-7523
Abstract:
7523 Background: Duvelisib (DUV), a first-in-class oral dual PI3K-δ,γ inhibitor, is approved for treatment (tx) of R/R CLL/SLL after ≥ 2 prior therapies. In the phase 3 DUO trial, DUV 25 mg BID significantly improved efficacy vs ofatumumab (OFA; mPFS, 13.3 vs 9.9 mo; HR, 0.52 [ P 〈 .0001]; ORR, 74% vs 45% [ P 〈 .0001]) in pts with R/R CLL/SLL. Tx-emergent AEs (TEAEs) of special interest (AESIs) such as infections, diarrhea, colitis, neutropenia, rash, ALT/AST elevation, and pneumonitis, were moderate and manageable with early intervention and dose modification. We examined dose-modification patterns and their impact on response to DUV in the DUO trial. Methods: Dose interruptions (DI) or reductions (DR) to 15, 10, or 5 mg BID were permitted per study protocol to manage TEAEs. Responses were assessed by IRC. Results: Among 158 DUV-treated pts, median duration of DUV exposure was 11.6 mo (vs 5.3 mo, OFA). DI and DR occurred in 80% (126/158) and 27% (43/158) of pts, respectively. The most common cause of DI was diarrhea (23%), followed by neutropenia (12%) and pneumonia or colitis (11% each). Among responders (n = 118), median time to first response on DUV was 1.9 mo and estimated median duration of response was 11.1 mo. Median time to first DI was 3.9 mo and median duration of DI was 15 d (range, 1-133 d). Response to DUV was improved or maintained in most pts evaluated for response who had ≥ 1 DI for 〉 1 wk (84% [42/50]) or 〉 2 wk (82% [31/38]) followed by ≥ 3 wk on DUV. In a landmark analysis, median PFS was similar in pts with DI and those without DI for 〉 1 wk (17.8 vs 16.3 mo) or 〉 2 wk (17.8 vs 16.3 mo) within the first 3 mo. The median time to DR after CR/PR was 5.6 mo (n = 25) and median duration was 3.4 mo. Median time to onset across AESIs after starting DUV ranged from 2.2 to 4.3 mo; median time to resolution was within 4 wk across AESIs. Proportions of pts experiencing AESIs were stable or decreased over time after 3-6 mo: 0-3 mo, 64% (101/158); 〉 3-6 mo, 63% (86/137); 〉 6-9 mo, 47% (54/114); 〉 9-12 mo, 52% (52/100), and seldom led to discontinuation of DUV (≤ 10%). Conclusions: DI/DR can contribute to the effective management of TEAEs with DUV. These findings suggest that DI of 〉 1-2 weeks or more do not appear to significantly impact response to DUV or PFS. Clinical trial information: NCT02004522.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.7523
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
