Abstract P2-13-03: The impact of neratinib with or without anti-diarrheal prophylaxis on health-related quality of life in HER2+ early-stage breast cancer: Analyses from the ExteNET and CONTROL trials
Authors: Delaloge S , Hurvitz S , Chan N , Bose R , Jankowitz RC , Thirlwell M , Láng I , ten Tije A , Trudeau M , Osborne CR , Shen Z-Z , Lalla D , Xu F , Hunt D , Olek E , Tripathy D , Rugo HS , Chien J , Chan A , Barcenas CH 
Published: May 2019

Abstract
Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor. ExteNET, a randomized placebo-controlled phase III study, showed that neratinib given for 12 months after trastuzumab-based adjuvant therapy significantly improved 2-year (HR 0.67; 95% CI 0.50–0.91; p=0.0091) and 5-year (HR 0.73; 95% CI 0.57-0.92; p=0.008) iDFS in pts with early-stage HER2+ breast cancer. Anti-diarrheal prophylaxis was not mandated by protocol; grade 3/4 diarrhea occurred in 40% of pts with a median cumulative duration of 5 days. The phase II CONTROL study was initiated to investigate the effectiveness of various prophylactic regimens in the prevention of neratinib-associated diarrhea. Loperamide (L) alone or in combination with add-on agents targeting underlying inflammation [i.e. budesonide (BUD)] or bile acid malabsorption [i.e. colestipol (COL)] were tested. We report longitudinal HRQoL findings from both ExteNET and CONTROL.
Methods: Pts with early-stage HER2+ breast cancer who had received trastuzumab-based adjuvant therapy were eligible for both studies. In ExteNET, pts received neratinib or placebo for 12 months. In CONTROL, pts received neratinib for 13 x 28-day cycles combined with L, L + BUD or L + COL for 1 or 2 cycles (see table for schedules). HRQoL was assessed using Functional Assessment of Cancer Therapy–Breast (FACT-B), v4.0, at baseline, months 1, 3, 6, 9, 12 (ExteNET) or baseline, cycles 2, 4, 7, 10, 13 (CONTROL). Changes in scores from baseline were considered to be clinically meaningful if greater than the lowest estimate for an 'important difference' (ID) reported in the literature. Evaluable pts were required to have HRQoL assessments at baseline and at least 1 post-baseline. ClinicalTrials.gov: NCT00878709 (ExteNET); NCT02400476 (CONTROL).
Results: HRQoL findings are summarized in the table. Hospitalization rates due to diarrhea: 1.5% (neratinib + L), 0% (other cohorts) in CONTROL; and 1.4% (neratinib), 0.1% (placebo) in ExteNET.
Mean change from baselineStudyCohort/GroupM1M3M6M9M12 FACT-B TOTAL (ID range: 7–8 points)CONTROLN + La,b (N=40)–3.8–4.5–1.5–2.5–3.3 N + L + BUDa,b,c (N=62)–6.0–4.9–1.6–3.6–4.5 N + L + COLa,b,d (N=125)–3.8–2.0–4.0–4.6–3.6 N + L prn + COLa,d (N=85)–1.8–1.54.0e––ExteNETN + L prna (N=1124)–4.6–3.4–3.5–3.3–3.7 P (N=1188)–1.7–3.5–2.9–2.9–2.8 FACT-B PWB (ID range: 2–3 points)CONTROLN + La,b (N=40)–4.0–2.3–1.9–2.4–2.3 N + L + BUDa,b,c (N=62)–3.2–2.1–1.4–1.7–1.7 N + L + COLa,b,d (N=125)–2.8–2.0–2.4–2.5–2.4 N + L prn + COLa,d (N=85)–2.8–1.80.0e––ExteNETN + L prna (N=1124)–2.9–1.9–1.7–1.6–1.5 P (N=1188)–0.6–0.8–0.7–0.6–0.4C, cycle; L, loperamide; M, month; N, neratinib; prn, as needed; PWB, physical well-being. CONTROL cut-off: 1 May 2018. aN 240 mg qd for 13 x 28d cycles or 12 months; bL 4 mg, then 4 mg tid d1-14, then 4 mg bid d15-28 or d15-56, then prn; cBUD 9 mg qd d1-28; dCOL 2 g qd d1-28; en=1.
Conclusions: Adjuvant neratinib with or without anti-diarrheal prophylaxis was associated with small decreases in HRQoL. With the exception of the FACT-B PWB subscale, HRQoL changes did not reach clinically meaningful thresholds. Follow-up in CONTROL is ongoing.
Citation Format: Delaloge S, Hurvitz S, Chan N, Bose R, Jankowitz RC, Thirlwell M, Láng I, ten Tije A, Trudeau M, Osborne CR, Shen Z-Z, Lalla D, Xu F, Hunt D, Olek E, Tripathy D, Rugo HS, Chien J, Chan A, Barcenas CH. The impact of neratinib with or without anti-diarrheal prophylaxis on health-related quality of life in HER2+ early-stage breast cancer: Analyses from the ExteNET and CONTROL trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-03.