SAN ANTONIO – The addition of pertuzumab to first-line trastuzumab and an aromatase inhibitor (AI) significantly improved progression-free survival compared with trastuzumab and an AI alone in patients with HER2-positive, hormone receptor (HR)-positive advanced breast cancer, a study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) has shown.1
“The TANDEM study showed that the addition of trastuzumab to anastrazole significantly improved progression-free survival vs anastrazole alone in HER2-positive, HR-positive metastatic breast cancer,” said Grazia Arpino, MD, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston. “The CLEOPATRA trial showed that the addition of pertuzumab to trastuzumab plus docetaxel significantly improved progression-free and overall survival vs trastuzumab plus docetaxel in first-line, HER2-positive metastatic breast cancer.”
Therefore, researchers hypothesized that pertuzumab plus trastuzumab and aromatase inhibitor could offer additional benefits to patients with HER2-positive, HR-positive breast cancer.
The phase 2 PERTAIN trial (ClinicalTrials.gov Identifier: NCT01491737) enrolled 258 postmenopausal women with HER2-positive, HR-positive, metastatic, or locally advanced breast cancer who had not received prior systemic therapy except for endocrine therapy. Participants were randomly assigned 1:1 to receive first-line pertuzumab plus trastuzumab and an aromatase inhibitor (anastrozole or letrozole), or trastuzumab plus an aromatase inhibitor, until disease progression or unacceptable toxicity.
Results showed that adding pertuzumab to trastuzumab and an AI significantly reduced the risk of progression or death by 35% vs treatment with trastuzumab and an AI alone (hazard ratio [HR], 0.65; 95% CI, 0.48-0.89; P =.0070).
“Pertuzumab plus trastuzumab plus an AI was superior to trastuzumab plus an AI in postmenopausal women with HER2-positive, HR-positive locally advanced or metastatic breast cancer,” said Dr Arpino.
Subgroup analyses further revealed that patients who chose not to receive induction chemotherapy and those who had been off adjuvant hormone therapy for at least 12 months particularly benefited from pertuzumab therapy.
Median progression-free survival was 18.89 months with the 3-drug combination vs 15.80 months with trastuzumab plus an AI. Median overall survival has not yet been reached in either arm.
In addition, 63.3% (95% CI, 53.5-72.3) of patients who received the 3-drug combination achieved a response compared with 55.7% (95% CI, 45.7-65.3) of those in the 2-drug treatment group, though this difference was not statistically significant (P =.25). Most responses were partial responses. Median duration of response was 27.1 months and 15.1 months in the pertuzumab arm and the trastuzumab only arm, respectively (hazard ratio, 0.57; 95% CI, 0.36-0.91; P =.02).
“Secondary efficacy end points supported the primary progression-free survival analysis,” Dr Arpino added.
Researchers found that 50.4% of patients who received trastuzumab and pertuzumab reported grade 3 or higher adverse events, vs 38.7% of those who received trastuzumab alone. Approximately 10% of patients who received pertuzumab discontinued treatment due to an adverse event and 26.8% required treatment interruption as a result of an adverse event. The most frequently reported grade 3 or higher adverse events were hypertension, diarrhea, and neutropenia.
“Pertuzumab plus trastuzumab plus an AI was well tolerated and no new safety signals were identified,” said Dr Arpino.
1. 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. Paper presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX.