Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KristinE study
Journal
Journal of Clinical Oncology
Journal Volume
37
Journal Issue
25
Pages
2206-2216
Date Issued
2019
Author(s)
Hurvitz S.A.
Martin M.
Jung K.H.
Harbeck N.
Valero V.
Stroyakovskiy D.
Wildiers H.
Campone M.
Boileau J.-F.
Fasching P.A.
Afenjar K.
Spera G.
Lopez-Valverde V.
Song C.
Trask P.
Boulet T.
Sparano J.A.
Fraser Symmans W.
Thompson A.M.
Slamon D.
Abstract
PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment. ? 2019 by American Society of Clinical Oncology.
SDGs
Other Subjects
carboplatin; docetaxel; pertuzumab; trastuzumab; trastuzumab emtansine; antineoplastic agent; carboplatin; docetaxel; epidermal growth factor receptor 2; ERBB2 protein, human; monoclonal antibody; pertuzumab; trastuzumab; adjuvant chemotherapy; adult; anemia; asthenia; cancer combination chemotherapy; cancer staging; Conference Paper; controlled study; diarrhea; disease exacerbation; disease free survival; drug dose reduction; drug efficacy; drug safety; drug tolerability; drug withdrawal; event free survival; fatigue; febrile neutropenia; female; follow up; good clinical practice; human; human epidermal growth factor receptor 2 positive breast cancer; hypertension; hypokalemia; loading drug dose; maintenance drug dose; major clinical study; neoadjuvant chemotherapy; neutropenia; neutrophil count; overall survival; patient-reported outcome; peripheral neuropathy; phase 3 clinical trial; platelet count; priority journal; quality of life; recurrent disease; risk factor; side effect; thrombocytopenia; treatment duration; treatment outcome; vomiting; aged; breast tumor; clinical trial; enzymology; Kaplan Meier method; metabolism; middle aged; multicenter study; neoadjuvant therapy; randomized controlled trial; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Chemotherapy, Adjuvant; Disease-Free Survival; Docetaxel; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoadjuvant Therapy; Receptor, ErbB-2; Trastuzumab
Publisher
American Society of Clinical Oncology
Type
conference paper