2019 ASCO: 3-Year Outcomes in the KRISTINE Trial on Neoadjuvant Trastuzumab Emtansine Plus Pertuzumab in HER2-Positive Breast Cancer
As reported at the 2019 ASCO Annual Meeting (Abstract 500) and in the Journal of Clinical Oncology by Hurvitz et al, 3-year outcomes in the phase III KRISTINE trial showed that neoadjuvant trastuzumab emtansine (T-DM1) plus pertuzumab was associated with increased risk of event-free survival events vs docetaxel/carboplatin/trastuzumab plus pertuzumab in patients with stage II or III HER2-positive breast cancer.
The original report from KRISTINE showed that T-DM1 plus pertuzumab was associated with a significantly lower pathologic complete response rate but fewer grade ≥ 3 and serious adverse events.
Study Details
In the trial, 444 patients were randomly assigned to neoadjuvant T-DM1 plus pertuzumab (n = 223) or docetaxel/carboplatin/trastuzumab plus pertuzumab (n = 221) every 3 weeks for six cycles. Patients who received T-DM1 plus pertuzumab continued adjuvant T-DM1 plus pertuzumab, and patients who received docetaxel/carboplatin/trastuzumab plus pertuzumab received adjuvant trastuzumab/pertuzumab.
Event-Free and Invasive Disease–Free Survival
Median follow-up was 37 months. Risk of an event-free survival event was higher with T-DM1 plus pertuzumab (hazard ratio [HR] = 2.61, 95% confidence interval [CI] = 1.36–4.98), reflecting more locoregional progression events before surgery (6.7% vs 0%) and noninvasive recurrent events after surgery (1.3% vs 0%). Event-free survival at 3 years was 85.3% in the T-DM1 plus pertuzumab group vs 94.2% in the docetaxel/carboplatin/trastuzumab plus pertuzumab group. Risk of an invasive disease–free survival event was similar in the two groups (HR = 1.11, 95% CI = 0.52–2.40). Three-year invasive disease–free survival was 93.0% vs 92.0%. Pathologic complete response was associated with reduced risk of an invasive disease–free survival events, irrespective of treatment group (HR = 0.24, 95% CI = 0.09–0.60).
Adverse Events
Overall, grade ≥ 3 adverse events were less common with T-DM1 plus pertuzumab (31.8% vs 67.7%). During adjuvant treatment, grade ≥ 3 adverse events (24.5% vs 9.9%) and adverse events leading to treatment discontinuation (18.4% vs 3.8%) were more common with T-DM1 plus pertuzumab vs docetaxel/carboplatin/trastuzumab plus pertuzumab.
The investigators concluded: “Compared with docetaxel/carboplatin/trastuzumab plus pertuzumab, T-DM1 plus pertuzumab resulted in a higher risk of an [event-free survival] event owing to locoregional progression events before surgery, a similar risk of an invasive disease–free survival] event, fewer Grade 3 or greater adverse events during neoadjuvant treatment, and more [adverse events] leading to treatment discontinuation during adjuvant treatment.”
Sara A. Hurvitz, MD, of the David Geffen School of Medicine, University of California, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by F. Hoffman-La Roche/Genentech. For full disclosures of the study authors, visit coi.asco.org or jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
