Results from a phase 2 trial of patients with HER2-positive breast comparing TCbH alone and TCbH with pyrotinib showed significant improvement when adding pyrotinib, according to data presented at ASCO.
Pyrotinib combined with trastuzumab (Herceptin), docetaxel, and carboplatin (TCbH) significantly improved the total pathological complete response (pCR) rate of patients with HER2-positive breast cancer compared with TCbH alone, according to the results of a phase 2 trial (NCT03756064) presented during the 2021 American Society of Clinical Oncology Annual Meeting.1
“In this study, TCbH plus pyrotinib neoadjuvant therapy significantly improved the total pCR rate of HER2-positive breast cancer patients for about twice [that of] TCbH with a manageable safety [profile],” the study authors, led by Xiaowen Ding, MD, of the Department of Breast Surgery, Zhejiang Cancer Hospital in Hangzhou, China, wrote in their poster.
The randomized, double-blind multicenter study evaluated the efficacy and safety of the addition of pyrotinib, an irreversible second-generation HER2-targeted tyrosine kinase inhibitor (TKI), to TCbH versus TCbH alone given as neoadjuvant treatment in patients with stage II-III HER2-positive breast cancer and invasive carcinoma. pCR, the primary end point, was defined in the study as no invasive or in situ disease in the breast or axilla. Secondary end points included toxicity, event-free survival, disease-free survival, distant disease-free survival, and objective response rate (ORR).
From 2019 to 2021, 67 patients with HER2-positive breast cancer were randomized equally into the treatment and control groups. Investigators hypothesized that patients treated in the investigational group (pyrotinib+TCbH) could have a higher pCR rate than the control group (TCbH). Their hypothesis proved true with the total pCR rate in the treatment group measuring 71.4% (15/21) versus 36.7% (11/30) in the control group; a significant difference was found between the 2 groups (P < .05).
In the treatment group (n = 34) patients received 6 cycles of 400 mg pyrotinib plus 6 mg/kg trastuzumab with a loading dose of 8 mg/kg, 75 mg/m docetaxel, and carboplatin at area under the curve 6. As of data cutoff, 21 patients had undergone surgery, 7 had not competed treatment (6 had not finished neoadjuvant therapy and 1 had not received surgery), and 6 withdrew consent and discontinued treatment. In the control group (n = 33), patients received the same 6 cycles of TCbH. Thirty patients had undergone surgery and 3 had not completed neoadjuvant therapy.
All patients (n = 21, 100%) in the treatment group achieved a response, while the control group showed an ORR of 83.3% (25/30). Four patients showed stable disease and 1 was evaluated as progressive disease in the control group.
The most common adverse event was diarrhea, with grade 3 events occurring in 6 cases (28.6%) in the treatment group, most of which were limited to the first treatment cycle. In the control group, 3 patients (10%) experienced grade 3 diarrhea.
Eligibility for the study included patients aged 18-70 years with stage II-III HER2-positive breast cancer, invasive carcinoma, and an ECOG performance status of 0-1. In the investigational group, at baseline, 22 patients (65%) were older than 50, and 12 (35%) were 50 or younger; 29 patients (85%) exhibited tumor size >2 cm, 5 patients (15%) ≤2 cm; 22 patients (64%) had about 1 to 2 positive lymph nodes, 6 (18%) had about 3 to 4, and 6 (18%) were node negative; and 21 patients (62%) had a negative hormone receptor (HR) status, while 13 patients (38%) were positive for HR.
In the control group, 18 patients (55%) were older than 50, 15 patients (45%) were 50 or younger; 30 patients (91%) showed a tumor size of >2 cm, 3 patients (9%) ≤2 cm; 21 patients (64%) had about 1 to 2 positive nodes, 9 (27%) had about 3 to 4 positive nodes, and 3 (9%) were node negative; and 17 patients (52%) had negative HR status, 16 patients (48%) reported positive.
Ding X, Mo W,Xie X, et al. Pyotinib as neoadjuvant therapy for HER2+ breast cancer: a multicenter, randomized controlled phase II trial. J Clin Oncol. 2021;39(suppl 15; abstr 574). doi:10.1200/JCO.2021.39.15_suppl.574