Arlene Chan (Nedlands, Australia)
Breast Cancer Research Centre BCRC - WAAuthor Of 1 Presentation
73P - Effect of diarrheal prophylaxis or dose escalation on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Final findings from the CONTROL trial (ID 88)
- Arlene Chan (Nedlands, Australia)
- Manuel Ruiz Borrego (Seville, Spain)
- Gavin Marx (Sydney, Australia)
- Adam Brufsky (Pittsburgh, United States of America)
- A Jo Chien (San Francisco, United States of America)
- Michael P. Thirlwell (Montreal, Canada)
- Maureen E. Trudeau (Toronto, Canada)
- Ron Bose (St. Louis, United States of America)
- Jose Angel Garcia Saenz (Madrid, Spain)
- Daniel Egle (Innsbruck, Austria)
- Barbara Pistilli (Villejuif, France)
- Johanna Wassermann (Paris, France)
- Kerry A. Cheong (Adelaide, Australia)
- Dieter Semsek (Freiburg im Breisgau, Germany)
- Christian F. Singer (Vienna, Austria)
- Daniel Diprimeo (South San Francisco, United States of America)
- Navid Foruzan (South San Francisco, United States of America)
- Leanne M. McCulloch (South San Francisco, United States of America)
- Carlos H. Barcenas (Houston, United States of America)
Abstract
Background
Neratinib (N), an irreversible pan-HER TKI, is approved in the EU for extended adjuvant treatment of early-stage HR+ HER2+ breast cancer (BC) after adjuvant trastuzumab (T)-based therapy. The CONTROL trial (NCT02400476) investigated pre-emptive antidiarrheal prophylaxis or dose escalation (DE) for prevention of diarrhea, the most frequent side effect of N.
Methods
CONTROL is an international, multi-cohort, open-label, phase 2 study. Patients (pts) ≥18y with stage I–IIIc HER2+ BC received oral N (240 mg/d for 1y) after T-based adjuvant therapy. Pts were enrolled sequentially into separate cohorts: 1) mandatory loperamide prophylaxis; 2) budesonide + loperamide; 3) colestipol + loperamide; 4) colestipol + loperamide PRN; 5) DE + loperamide PRN (2 cohorts). DE1 schedule: N 120 mg/d x w1, 160 mg/d x w2, then 240 mg/d from w3 to 12m. DE2 schedule: N 160 mg/d x w1&2, 200 mg/d x w3&4, then 240 mg/d from w5 to 12m. Primary endpoint: incidence of grade ≥3 diarrhea.
Results
563 pts were enrolled. All preventive strategies reduced grade 3 diarrhea vs ExteNET (historical control: 39%). Median cumulative duration of grade 3 diarrhea ranged from 2–3.5d in CONTROL (vs 5.0d for ExteNET). The proportion of pts discontinuing N because of diarrhea was decreased in CONTROL vs ExteNET. Key diarrhea outcomes in all CONTROL cohorts are presented in the table and will be fully detailed during the congress. Patient disposition and diarrhea characteristics: All CONTROL cohorts
Loperamide (n=137) Budesonide Colestipol Colestipol + loperamide PRN (n=104) DE1 + loperamide PRN (n=60) DE2 + loperamide PRN (n=62) Median duration of treatment, months (Q1–Q3) 11.6 (0.8–12.0) 12.0 (11.8–12.0) 11.9 (8.5–12.0) 12.0 (8.3–12.0) 12.0 (11.1–12.0) 11.9 (7.5–12.0) Diarrhea, n (%) Grade 3 42 (30.7) 18 (28.1) 28 (20.6) 34 (32.7) 8 (13.3) 17 (27.4) Grade ≥4 0 0 0 0 0 0 Median cumulative duration of grade 3 diarrhea, days 3.0 3.0 3.5 2.0 2.5 2.0 Discontinuations due to diarrhea, n (%) 28 (20.4) 7 (10.9) 5 (3.7) 8 (7.7) 2 (3.3) 4 (6.5) Dose reductions due to diarrhea, n (%) 10 (7.3) 2 (3.1) 10 (7.4) 10 (9.6) 2 (3.3) 7 (11.3)
Conclusions
These final findings from CONTROL show improved tolerability of N with all diarrhea prophylaxis strategies and suggest that DE1 with loperamide PRN allows pts to stay on treatm.ent longer and receive full benefit from N.
Clinical trial identification
NCT02400476.
Editorial acknowledgement
Editorial/writing assistance for this abstract was provided by Lee Miller (Miller Medical Communications Ltd.). This work was funded by the study sponsor (Puma Biotechnology Inc.).
Legal entity responsible for the study
Puma Biotechnology Inc.
Funding
Puma Biotechnology Inc.
Disclosure
A. Brufsky: Financial Interests, Personal, Advisory Role, Consulting fees: Puma Biotechnology Inc. A.J. Chien, R. Bose: Financial Interests, Institutional, Research Grant: Puma Biotechnology Inc. B. Pistilli: Financial Interests, Personal, Advisory Role, Consulting fees: Puma Biotechnology Inc.; Financial Interests, Personal, Advisory Role, Consulting fees: Pierre Fabre; Financial Interests, Institutional, Research Grant: Puma Biotechnology Inc. D. Diprimeo, N. Foruzan, L.M. McCulloch: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.