Incidence and Management of Diarrhea With Adjuvant Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Abstract

BACKGROUND:

The APHINITY (BIG 4-11) study showed that pertuzumab significantly improved the rates of invasive disease-free survival among patients with human epidermal growth factor receptor 2 (HER2)-positive, operable breast cancer when added to adjuvant trastuzumab and chemotherapy. Because diarrhea was a common adverse event that could compromise treatment administration, we evaluated the incidence and management of diarrhea in the APHINITY study.

PATIENTS AND METHODS:

The APHINITY trial is a prospective, randomized, multicenter, multinational, double-blind, placebo-controlled trial. The eligible patients were randomly assigned to receive standard adjuvant chemotherapy and 1 year of trastuzumab combined with pertuzumab or placebo. The diarrhea incidence, severity (National Cancer Institute common terminology criteria for adverse events, version 4.0), onset, and management were analyzed.

RESULTS:

A total of 4805 patients were randomized. Diarrhea of any grade was the most common adverse event and occurred in 71% of patients in the pertuzumab arm versus 45% in the placebo arm. Diarrhea grade 3 to 4 was observed in 10% and 4% in the pertuzumab and placebo arms, respectively. The greatest incidence of diarrhea was reported during the concomitant administration of HER2-targeted therapy and taxane (61% vs. 34% of patients experienced an event with pertuzumab vs. placebo, respectively). A marked decrease was observed on chemotherapy cessation. Antidiarrheal agents were commonly used, and diarrhea rarely caused treatment dose modifications or discontinuation.

CONCLUSION:

Diarrhea was a common adverse event in the APHINITY study. Most episodes were low grade and were generally manageable with common antidiarrheal agents. The incidence of diarrhea was greater with the combination of a taxane and HER2-targeted treatment and decreased once chemotherapy was stopped.

• Authors: José Bines, Marion Procter, Eleonora Restuccia, Giuseppe Viale, Dimitrios Zardavas, Thomas Suter, Amal Arahmani, Veerle Van Dooren, José Baselga, Emma Clark, Jennifer Eng-Wong, Richard D Gelber, Martine Piccart, Volker Mobus, Evandro de Azambuja, APHINITY Steering Committee and Investigators
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 20 Issue 2 Pg. 174-181.e3 (04 2020) ISSN: 1938-0666 [Electronic] United States
• PMID: 31924513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antidiarrheals
• Bridged-Ring Compounds
• Taxoids
• taxane
• ERBB2 protein, human
• Receptor, ErbB-2
• pertuzumab
• Trastuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antidiarrheals (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast (pathology, surgery)
• Breast Neoplasms (mortality, pathology, therapy)
• Bridged-Ring Compounds (adverse effects)
• Chemotherapy, Adjuvant (adverse effects, methods)
• Diarrhea (chemically induced, diagnosis, drug therapy, epidemiology)
• Disease-Free Survival
• Female
• Humans
• Incidence
• Mastectomy
• Middle Aged
• Multicenter Studies as Topic
• Progression-Free Survival
• Prospective Studies
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (antagonists & inhibitors, metabolism)
• Severity of Illness Index
• Taxoids (adverse effects)
• Trastuzumab (adverse effects)