Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).

Authors

Nadia Harbeck

Nadia Harbeck

Brustzentrum der Universität München (LMU), Munich, Germany

Nadia Harbeck , Seock-Ah Im , Carlos H. Barrios , Herve R. Bonnefoi , Julie Gralow , Masakazu Toi , Paul Ellis , Luca Gianni , Sandra M. Swain , Young-Hyuck Im , Michelino De Laurentiis , Zbigniew Nowecki , Jigna Shah , Thomas Boulet , Haiying Liu , Harrison Macharia , Peter Trask , Chunyan Song , Eric P. Winer , Ian E. Krop

Organizations

Brustzentrum der Universität München (LMU), Munich, Germany, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea, Hospital do Câncer Mãe de Deus Centro de Pesquisa Clínica Hospital São Lucas, Porto Alegre, Brazil, Institut Bergonié Unicancer and Bordeaux University, Bordeaux, France, Seattle Cancer Care Alliance, Seattle, WA, Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan, Guy’s Hospital and Sarah Cannon Research Institute, London, United Kingdom, Fondazione Michelangelo, Milan, Italy, NSABP/NRG Oncology, and The Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC, Samsung Medical Center, Seoul, South Korea, National Cancer Institute “Fondazione Pascale,” Department of Breast and Thoracic Oncology, Naples, Italy, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland, Genentech, Inc., South San Francisco, CA, F. Hoffmann-La Roche Ltd., Basel, Switzerland, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Dana-Farber Cancer Institute, Boston, MA

Research Funding

Pharmaceutical/Biotech Company
F. Hoffmann-La Roche

Background: The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1. Methods: KAITLIN (NCT01966471) is a phase 3, randomized, open-label study that enrolled 1846 patients with adequately excised, centrally confirmed HER2-positive EBC either node-positive (LN+); or node-negative, HR-negative, and tumor size > 2.0 cm. Within 9 weeks of surgery, patients were randomized 1:1 to 3-4 cycles of anthracycline-based chemotherapy followed by 18 cycles of T-DM1 3.6 mg/kg + pertuzumab 420 mg q3w (loading dose [LD] 840 mg) (AC-KP) or taxane (3-4 cycles) + concurrent trastuzumab 6 mg/kg (LD 8 mg/kg) + pertuzumab 420 mg q3w (LD 840 mg) (AC-THP). Patients were stratified by world region, nodal status, HR status, and anthracycline type. Adjuvant radiotherapy and/or endocrine therapy was administered after 4 cycles of HER2-targeted therapy when indicated. The co-primary endpoints were invasive disease-free survival (IDFS) in the LN+ and in the ITT populations applying a hierarchical testing procedure. Secondary endpoints included overall survival (OS), patient-reported outcomes (PROs), and safety. Results: KAITLIN did not meet its co-primary endpoints. In LN+ patients (n = 1658), there was no significant difference between arms in IDFS event risk (stratified hazard ratio = 0.97; 95%CI 0.71–1.32). Three-year IDFS was 94.1% with AC-THP and 92.7% with AC-KP. Results were similar in the ITT population (stratified hazard ratio = 0.98; 95%CI 0.72–1.32; 3-year IDFS: 94.2% vs 93.1%). OS data are immature with an event rate of ~4%–5% in each arm. During the study overall, there was a similar incidence of grade ≥3 AEs (55.4% vs 51.8%) and SAEs (23.3% vs 21.4%) with AC-THP and AC-KP, respectively. More patients receiving AC-KP than AC-THP discontinued T-DM1 or trastuzumab, respectively, because of AEs (26.8% vs 4.0%). PRO data will be presented. Conclusions: Replacing adjuvant taxane and trastuzumab with T-DM1 did not result in significantly improved efficacy or overall safety. Nonetheless, in this high-risk population, a favorable IDFS outcome was achieved in both study arms. HP + chemotherapy remains the standard of care for patients with high-risk HER2-positive EBC. Clinical trial information: NCT01966471.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Oral Abstract Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Adjuvant Therapy

Clinical Trial Registration Number

NCT01966471

Citation

J Clin Oncol 38: 2020 (suppl; abstr 500)

DOI

10.1200/JCO.2020.38.15_suppl.500

Abstract #

500

Abstract Disclosures