A statistically significant improvement in the total pathologic complete response rate, the primary end point of the study, was observed with neoadjuvant treatment of pertuzumab, trastuzumab and docetaxel compared with placebo, trastuzumab, and docetaxel in Asian patients with <a><em>ERBB2</em></a> -positive early or locally advanced breast cancer, according to the phase III PEONY trial.
A statistically significant improvement in the total pathologic complete response (tpCR) rate, the primary end point of the study, was observed with neoadjuvant treatment of pertuzumab (Perjeta), trastuzumab (Herceptin) and docetaxel compared with placebo, trastuzumab, and docetaxel in Asian patients withERBB2-positive early or locally advanced breast cancer, according to the phase III PEONY trial (NCT02586025).
“The PEONY trial met its primary end point, providing, to our knowledge, the first efficacy data from a randomized, placebo-controlled, phase 3 study of the addition of pertuzumab vs placebo to trastuzumab and docetaxel in the neoadjuvant setting in an Asian population withERBB2-positive [early breast cancer] or [locally advanced breast cancer]; adding pertuzumab resulted in a statistically significant improvement in the tpCR rate,” study authors wrote.
The tpCR rate was 39.3% in the pertuzumab arm versus 21.8% with placebo, a 17.5% difference (95% CI, 6.9%-28.0%;P=.001).
Objective responses were reached in 88.6% of patients in the pertuzumab arm (95% CI, 83.6%-92.5%) and 78.2% in the placebo arm (95% CI, 69.3%-85.5%), with a difference of 10.4% (95% CI, 1.1%-19.7%). Clinical CR rates were reached in 11.0% of patients in the pertuzumab arm (95% CI, 7.2%-15.9%) versus 10.0% with placebo (95% CI, 5.1%-17.2%). Clinical partial response rates were observed in 77.6% of patients in the experimental arm (95% CI, 71.5%-83.0%) versus 68.2% in the placebo arm (95% CI, 58.6%-76.7%).
The most common AEs appeared similar between the 2 arms, but there was a higher incidence of diarrhea, a common AE associated with pertuzumab, in the experimental arm arm (38.5%) compared with placebo (16.4%), most of which was either grade 1 (26.6% versus 11.8%) or grade 2 (11.0% versus 4.5%), respectively. Grade 3 diarrhea was noted in 0.9% of patients in the pertuzumab arm.
The most common AEs reported in the pertuzumab versus placebo arms included alopecia (49.1%vs. 49.1%), neutropenia (48.2% vs. 44.5%), leukopenia (42.2% vs. 39.1%), diarrhea (38.5% vs. 16.4%), anemia (24.3% vs. 27.3%), alanine aminotransferase increase (22.5% vs. 23.6%), nausea (20.6% vs. 19.1%), aspartate aminotransferase increase (17.0% vs. 20.0%), pyrexia (14.2% vs. 10.0%), and upper respiratory tract infection (15.1% vs. 6.4%).
In addition, the most common grade 3 or greater adverse event (AE) was neutropenia, observed in 38.1% of patients in the experimental arm versus 32.7% with placebo, while serious AEs were noted in 10.1% versus 8.2% of patients, respectively.
Infusion-related reactions were observed in 22.0% of patients in the pertuzumab arm versus 9.1% in the placebo arm. Grade 3 or greater AEs occurred in 48.6% in the pertuzumab arm versus 41.8% in the placebo arm, the most common occurring in at least 3 patients, included neutropenia and leukopenia (20.6% vs. 19.1%), respectively. The most common serious AE was febrile neutropenia, which occurred in 1.8% with pertuzumab versus 0.9% with placebo.
Only 1 death occurred during the study, including a patient from the pertuzumab arm.
PEONY was a randomized, placebo-controlled clinical trial evaluating the addition of pertuzumab to treatment in the neoadjuvant setting for an Asian population. Overall, 329 patients were randomized to either pertuzumab in addition to trastuzumab and docetaxel chemotherapy (n = 219) or placebo plus trastuzumab and docetaxel (n = 110). Baseline demographics and disease characteristics appeared generally well balanced across the 2 arms, and most patients had received 4 treatment cycles.
The purpose of this clinical trial was to evaluate the efficacy, safety, and tolerability of adding pertuzumab to the combination of trastuzumab plus docetaxel in the Asian population. Prior studies, such as the phase II NeoSphere clinical trial (NCT00545688), indicated that this neoadjuvant combination led to significantly increased breast pathologic CR compared to the doublet of trastuzumab and chemotherapy alone. Pertuzumab initially received itsapproval from the FDA in the breast cancer spacebased on the NeoSphere trial.
“These data are consistent with previous pertuzumab studies and support the conclusion that pertuzumab is efficacious inERBB2-positive early breast cancer across races,” the study authors concluded.
Shao Z, Pang D, Yang H, et al. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia:The PEONY Phase 3 Randomized Clinical Trial [Published Online October 24, 2019].Jama Oncology. doi:10.1001/jamaoncol.2019.3692.