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Phase III results of the KRISTINE trial demonstrated that patients with HER2-positive early breast cancer had a significantly higher pathological complete response rate when they received the neoadjuvant regimen of docetaxel, carboplatin, and trastuzumab plus pertuzumab versus trastuzumab emtansine plus pertuzumab.
Sara A. Hurvitz, MD
Phase III results of the KRISTINE trial demonstrated that patients with HER2-positive early breast cancer had a significantly higher pathological complete response (pCR) rate when they received the neoadjuvant regimen of docetaxel, carboplatin, and trastuzumab plus pertuzumab (TCH+P) versus trastuzumab emtansine (T-DM1) plus pertuzumab (T-DM1+P).
While the TCH+P regimen was also associated with a higher rate of breast conserving surgery, researchers reported that T-DM1+P had a notably better safety profile and that health-related quality of life and physical functioning were maintained longer.
“Neoadjuvant TCH+P achieved a superior pCR rate compared with T-DM1+P and was associated with a higher breast-conserving-surgery rate,” said Sara A. Hurvitz, MD, General Internal Medicine, Hematology & Oncology, UCLA Medical Center. “However, neoadjuvant T-DM1+P had a more favorable safety profile, with lower incidence of grade 3 or greater adverse events, serious adverse events, and adverse events leading to treatment discontinuation.”
T-DM1 and pertuzumab bind to different HER2 domains and have marked antitumor activity in HER2-positive breast cancer. KRISTINE, results of which were presented at the 2016 ASCO Annual Meeting, shows the first phase III data for a neoadjuvant regimen that omits standard chemotherapy for HER2-positive breast cancer.
From June 2014 to June 2015, researchers at 68 centers in 10 countries enrolled 444 patients with centrally confirmed HER2-positive breast cancer greater than 2 cm in size. Patients were randomly assigned to receive T-DM1+P or the TCH+P regimen. Both regimens were given every 3 weeks for 6 cycles. At the end of the first cycle, patients underwent a core needle biopsy of the tumor for biomarker endpoints.
After 6 cycles, patients received standard of care surgery, and after surgery, they went on to receive 12 more doses of HER2-directed therapy according to the arm they were in. Patients in the T-DM1+P arm who had significant residual disease at the time of the surgery were encouraged to receive standard chemotherapy before receiving a maintenance therapy regimen.
Baseline characteristics were well distributed to 2 treatment arms by age, world region, estrogen receptor (ER)/progesterone receptor (PR) status, and stage.
The pCR rate in the breast and lymph nodes was 56% in the TCH+P arm and 44% in the T-DM1+P arm. This 11% difference was statistically significant, said Hurvitz, favoring the TCH+P arm.
In patients with ER- and PR-negative breast cancer, TCH+P yielded a pCR of 73% in breast and lymph nodes compared with 54% in the T-DM1+P arm.
In hormone receptor (HR)—positive breast cancer, the pCR was 44% in the TCH+P arm and 35% in the T-DM1+P arm, also favoring TCH+P. Over 60% of patients had HR-positive breast cancer, Hurvitz noted.
A preplanned, subgroup analysis showed that the benefits seen with TCH+P tended to favor all subgroups (age, world region, clinical stage at diagnosis and HR status). In addition, more women in the TCH+P underwent breast-conserving surgery (52.6% vs 41.7%, P = .0228).
In contrast, neoadjuvant T-DM1+P was associated with longer maintenance of patient-reported health-related quality of life and physical functioning, said Hurvitz. Neoadjuvant T-DM1+P also had a more favorable safety profile with a lower rate of grade 3/4 adverse events (AEs) (13% vs. 64%), serious AEs (5% vs. 29%), and AEs leading to treatment discontinuation (3% vs. 9%).
Cardiac event rates were unusual and were similar in the 2 treatment arms. Grade 3/4 AEs occurring in at least 3% of patients in either treatment arm included febrile neutropenia, neutropenia, diarrhea, and cytopenias, all of which were more common in the traditional chemotherapy arm compared with the T-DM1+P regimen.
Biomarker data and longer-term follow-up will be reported at a later date, said Hurvitz. In addition, there are several studies evaluating the use of T-DM1 in the early stage setting, including the KATHERINE and KAITLIN trials.
Hurvitz SA, Martin M, Symmans WF, et al. Pathologic complete response (pCR) rates after neoadjuvant trastuzumab emtansine (T-DM1 [K]) + pertuzumab (P) vs docetaxel + carboplatin + trastuzumab + P (TCHP) treatment in patients with HER2-positive (HER2+) early breast cancer (EBC) (KRISTINE). J Clin Oncol 34, 2016 (suppl; abstr 500).