Abstract P4-14-14: Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab
Authors: Swain SM , Schneeweiss A , Gianni L , Stein A , McNally V , Heeson S , Portera C , Yoo B , Cortes JC , Baselga J 
Published: May 2016

Abstract
BACKGROUND:
Pertuzumab (P) in combination with trastuzumab (T) and docetaxel (D) is the approved first line SOC in patients with HER2 positive metastatic breast cancer and is approved neoadjuvantly in patients with HER2 positive stage Ib-IIIc breast cancer. Because of its role in heterodimerization with EGFR, P may cause adverse events associated with EGFR antagonists. Diarrhea is the most commonly reported AE due to P. Increased usage of P has generated clinical questions regarding the incidence and management of diarrhea. Here we report safety analyses of diarrhea from three P containing studies.
METHODS: The safety population evaluated in this exploratory analysis included 804 patients from CLEOPATRA, 416 patients from NeoSphere, and 223 from TRYPHAENA. Diarrhea incidence, severity (NCI-CTCAE v3.0), and management in P containing arms were analyzed.
RESULTS: The incidence and management of diarrhea in MBC (Table 1), EBC (Table 2):
CLEOPATRA P+T+D n=408Pla+T+D n=396Incidence of Events n (%)All Grades279 (68)193 (49)≥ Grade 338 (9)20 (5)Median time to 1st event (days) all grades / Interquartile Range (IQR)8 (4,44)23 (6,82)Discontinuation of any study drug8 (0.2)2 (0.6)Treatment n (%)Antidiarrheal treatment164 (40)77 (19)
NeoSphere X4 followed by adjuvant FECx3TRYPHAENANeoadjuvant tx followed by T up to 1 yearT+D n=107P+T+D n=107P+T n=108P+D n=94FEC+P+T x3→P+T+D x3 n=72FEC x3 →P+T+D x3 n=75TCH+P x6 n=76Incidence of Events n (%) (neoadjuvant + adjuvant exposure)All Grades41 (38)55 (51)46 (43)53 (56)46 (64)47 (63)55 (72)≥ Grade 34 (4)7 (7)3 (3)5 (5)3 (4)4 (5)9 (12)Median time to 1st event (days) all grades / Interquartile Range (IQR)7 (4,24)8 (3,26)19 (4,117)6 (3,21)9 (4,30)69 (64,82)6 (3,21)Discontinuation of any study drug0000000Treatment n (%)Antidiarrheal treatment13 (12)23 (22)20 (19)28 (30)23 (32)22 (29)31 (41)pertuzumab(P)+trastuzumab(T)+docetaxel(D) FEC= 5FU, epirubicin, cyclophosphamide TCH= docetaxel,(T)carboplatin(C), trastuzumab(H)
The overall incidence of diarrhea events is greatest in the first cycle containing P: in CLEOPATRA (P+T+D) 43%, in NeoSphere (P+T+D) 34%, (P+T) 21%, and in TRYPHAENA (FEC+P+T→P+T+D) 40%, (FEC→P+T+D c4) 46%, and (TCH+P) 55%. Of patients experiencing diarrhea, the median number of events (all grades) for patients receiving P+T+D in CLEOPATRA and NeoSphere was 2 and 1 respectively, and 2 for patients receiving TCH+P in TRYPHAENA.
CONCLUSIONS:
Diarrhea was common in all P containing arms but events were mostly low grade and occurred more often with the first cycle. Events and management were similar in the EBC and MBC setting. Approximately half of patients required antidiarrheal treatment. However, rates of study drug discontinuation due to diarrhea were low. Studies of treatment associated diarrhea management are planned.
Citation Format: Swain SM, Schneeweiss A, Gianni L, Stein A, McNally V, Heeson S, Portera C, Yoo B, Cortes JC, Baselga J. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-14.