PERTAIN study: Pertuzumab in combination with trastuzumab and an aromatase inhibitor significantly prolongs progression-free survival
Results from the PERTAIN study demonstrated that the first-line combination of pertuzumab, trastuzumab and an aromatase inhibitor was effective and well-tolerated in patients with HER2-positive, hormone receptor-positive, locally advanced or metastatic breast cancer. Preclinical and clinical evidence suggest that cross-talk between HER2 and estrogen receptor signaling pathways in breast cancer contributes to treatment resistance. First-line treatment with pertuzumab in addition to trastuzumab and docetaxel significantly improved progression-free survival (PFS) and overall survival (OS) compared with trastuzumab and docetaxel in patients with HER2-positive metastatic breast cancer. In the PERTAIN study, the effect of adding an aromatase inhibitor instead of, or after, chemotherapy was assessed.
Patients (N=258) with HER2-positive, hormone receptor-positive, locally advanced or metastatic breast cancer who had not received prior systemic therapy (except endocrine therapy) were randomized 1:1 to arm A: pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) + trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks) + an aromatase inhibitor (anastrozole 1 mg daily or letrozole 2.5 mg daily) or arm B: trastuzumab + an aromatase inhibitor. Induction taxane or paclitaxel could be given weekly for 18 to 24 weeks at the investigator’s discretion before the start of endocrine therapy. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was PFS, stratified by induction chemotherapy (yes/no) and time since adjuvant hormone therapy (
Induction taxane and paclitaxel were received by 42 (32.6%) and 32 (24.8%) patients in arm A, respectively, and 37 (28.7%) and 31 (24.0%) patients in arm B. In arm A, PFS was 18.9 months, compared to 15.8 months in arm B (HR 0.65; 95%CI 0.48–0.89; p=0.007), meaning that the PERTAIN study reached its primary endpoint. Median OS was not reached in either arm. ORR was 63.3% (95% CI 53.5–72.3) in arm A and 55.7% in arm B (95% CI 45.7–65.3; p=0.25). Median DoR was 27.1 months in arm A and 15.1 months in arm B (HR 0.57; 95% CI 0.36–0.91; p=0.02). All grade adverse events (AEs) occurred in 122 patients in each arm (96.1% in arm A and 98.4% in arm B); grade ≥3 AEs in 64 (50.4%) and 48 (38.7%) patients respectively. The most common grade ≥3 AEs (≥5%; arm A versus arm B) were hypertension (10.2% versus 11.3%), diarrhea (7.1% versus 2.4%), and neutropenia (3.1% versus 6.5%).
In summary, data from the PERTAIN study demonstrated that the combination of pertuzumab, trastuzumab and an aromatase inhibitor is effective and well-tolerated and may offer a novel treatment option for patients with HER2-positive, hormone receptor-positive, locally advanced or metastatic breast cancer.
Arpino G, Ferrero JM, de la Haba-Rodriguez J, et al. Primary analysis of PERTAIN: A randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in first-line patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer. San Antonio Breast Cancer Symposium 2016, abstract S3-04.