Abstract P1-13-07: Incidence and management of diarrhea with adjuvant pertuzumab and trastuzumab in HER2-Positive breast cancer
Authors: Bines J , de Azambuja E , Zardavas D , Procter M , Restuccia E , Viale G , Suter T , Arahmani A , van Dooren V , Clark E , Eng-Wong J , Gelber R , Piccart M , von Minckwitz G , Baselga J 
Published: February 2018

Abstract
Background
Diarrhea is the most commonly reported adverse event (AE) on pertuzumab (Ptz) in both early and metastatic breast cancer (BC) settings. We report safety analyses of diarrhea from the large adjuvant APHINTY study in HER2 positive early breast cancer (EBC).
Patients and methods
In this exploratory analysis, the safety population included 2364 patients in the Ptz arm and 2405 in the placebo (Pla) arm. No specific prophylaxis was mandated by the protocol, however early intervention with loperamide as well as fluid and electrolyte replacement was recommended. Diarrhea incidence, severity (NCI-CTCAE v4.0), onset and management were analyzed.
Results
Diarrhea was the most common AE in the Ptz arm (71.3% vs. 45.2% in the Pla arm) and the events were mostly G1. Diarrhea ≥G3 was observed in 9.8% and 3.7% in Ptz and Pla arms, respectively. The highest incidence was reported during administration of HER2 targeted therapy and taxane (61.4% vs. 33.8% with Ptz and Pla, respectively) with a marked decrease observed upon chemotherapy cessation (18.1% vs. 9.2% with Ptz and Pla, respectively). The median time from first targeted treatment to onset of diarrhea during the chemotherapy phase was 7 and 10 days (Ptz/Pla). On average, diarrhea events lasted longer in the Ptz than in the Pla arm (median 8 vs. 6 days). Diarrhea events were more frequent with the administration of docetaxel + carboplatin and targeted agents, irrespective of the severity. Detailed results are reported in Table 1.
Conclusions
In the curative setting, diarrhea due to Ptz was mild, generally manageable with common antidiarrheals and did not affect patients' ability to receive treatment. The APHINITY findings are consistent with the well-characterized pattern of pertuzumab-related diarrhea across the HER2 BC spectrum.
Diarrhea incidence, severity (NCI-CTCAE v4.0), onset and management Ptz, n=2364Pla, n=2405Incidence and severityTotal number of patients with at least one adverse event$1685 (71.3%)1086 (45.2%)Total number of events$34151792NCI CTC AE Grade (highest grade per patient)!n1683 (71.2%)1085 (45.1%)Grade 1829 (35.1%)690 (28.7%)Grade 2622 (26.3%)305 (12.7%)Grade 3229 (9.7%)90 (3.7%)Grade 43 (0.1%)0Onset and duration$Median time (days) from 1st HER2 targeted treatment to onset (min-max)7 (1 – 358)10 (1 - 384)Median Duration (days) of each event (min-max)8 (1 - 811)6 (1 - 1022)ManagementAntidiarrheals$898 (38.0%)386 (16.0%)Dose modification* of any study drug!210 (8.9%)74 (3.1%)Dose modification* of HER2 targeted treatment!69 (2.9%)18 (0.7%)Discontinuation of any study drug!38 (1.6%)7 (0.3%)Discontinuation of HER2 Targeted treatment!20 (0.8%)2 (&lt;0.1%)$ Based on a basket of preferred terms for diarrhea ! Based only on the preferred term diarrhea * Includes dose reductions (chemotherapy only), delays or interruptions during infusion
Citation Format: Bines J, de Azambuja E, Zardavas D, Procter M, Restuccia E, Viale G, Suter T, Arahmani A, van Dooren V, Clark E, Eng-Wong J, Gelber R, Piccart M, von Minckwitz G, Baselga J. Incidence and management of diarrhea with adjuvant pertuzumab and trastuzumab in HER2-Positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-07.