First-line pertuzumab, as part of a complex chemotherapeutic regimen, improved progression-free survival (PFS) and overall survival (OS) in postmenopausal women with hormone receptor (HR)-positive, HER2-positive locally advanced and metastatic breast cancer. These are among the results of the PERTAIN trial, presented at the 2016 San Antonio Breast Cancer Symposium.
The investigators, led by Grazia Arpino, MD, from the Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, asserted that the regimen may offer a new therapeutic option for patients with HER2-positive/HR-positive (locally advanced/metastatic breast cancer).
Dr Arpino noted that HER2-estrogen receptor crosstalk may contribute to resistance to hormonal therapies and anti-HER2 therapies in breast cancer. The TANDEM study showed that the addition of trastuzumab to anastrozole significantly improved PFS versus anastrozole alone in HER2-positive/HR-positive metastatic breast cancer. In addition, “the CLEOPATRA trial showed that the addition of pertuzumab to trastuzumab plus docetaxel significantly improved PFS and OS over trastuzumab and docetaxel in first-line, HER2-positive metastatic breast cancer,” she said.
The results of the PERTAIN trial appear to show that pertuzumab plus trastuzumab plus an aromatase inhibitor is effective and well-tolerated, and may offer a novel treatment option for this important subset of patients with breast cancer.
The PERTAIN Trial
As a result of the findings from TANDEM and CLEOPATRA, 2 teams examined the effects of first-line pertuzumab, with or without trastuzumab and docetaxel, on outcomes in patients with HER2-positive metastatic breast cancer. Results showed significantly improved PFS and OS when pertuzumab was given with both trastuzumab and docetaxel.
The PERTAIN trial is the first to assess the efficacy of first-line pertuzumab with trastuzumab and an aromatase inhibitor, with or without taxane induction, in postmenopausal women who had locally advanced or metastatic HR-positive/HER2-positive breast cancer. The trial was conducted at 80 sites across 8 countries.
Patients who had not received prior systemic therapy (except endocrine therapy) in the advanced setting, had an ECOG performance status of 0 or 1, a left ventricular ejection fraction ≥50%, and a life expectancy of at least 12 weeks were randomly assigned to 1 of 2 groups:
- Group 1 (n = 129) received pertuzumab with trastuzumab and an aromatase inhibitor, with or without taxane induction
- Group 2 (n = 129) received trastuzumab and an aromatase inhibitor.
Intent-to-treat populations and safety populations yielded 127 patients and 124 patients, respectively.
A higher proportion of patients in the pertuzumab arm received anthracyclines (41.1%) and trastuzumab (31.1%) compared with those in the dual therapy arm (27.9% and 24.8%, respectively). Approximately 55% of patients in each arm received induction chemotherapy with pertuzumab and trastuzumab or trastuzumab alone.
The study met the primary end point of PFS. Secondary end points included OS, objective response rate, duration of response, and safety and tolerability. Baseline demographics and disease characteristics were generally balanced between arms. Treatment was continued until disease progression or unacceptable toxicity. Treatment was continued until investigators observed disease progression or patients reported unacceptable toxicity.
“The primary analysis in the intention-to-treat population showed that the addition of pertuzumab led to significant increase in median PFS of 3.09 months,” said Dr Arpino. PFS was 15.8 months in the control arm and 18.9 months in the pertuzumab arm. The hazard ratio for the primary end point was 0.65 (P = .007). The PFS advantage to the addition of pertuzumab was generally consistent across subgroups, including those not receiving induction chemotherapy.
Median OS was not reached in either group. The objective response rate was 63.3% (95% confidence interval [CI], 53.5-72.3) in group 1 and 55.7% in group 2 (95% CI, 45.7-65.3; P = .25). Median duration of response was 27.1 months in group 1 and 15.1 months in group 2 (hazard ratio, 0.57; 95% CI, 0.36-0.91; P = .02).
All-grade adverse events occurred in 122 patients in each arm (96.1% in group 1 and 98.4% in group 2). Adverse events grade ≥3 occurred in 64 (50.4%) and 48 (38.7%) patients in group 1 and group 2, respectively. However, rates of discontinuation or interruption of pertuzumab due to an adverse event were 10.2% and 26.8%, respectively, Dr Arpino noted. The most common adverse events grade ≥3 (≥5% in both groups) were hypertension (10.2% and 11.3%), diarrhea (7.1% and 2.4%), and neutropenia (3.1% and 6.5%).
“Cardiac safety was encouraging; in fact, in approximately 90% of patients, left ventricular ejection fraction remained above 45%,” she said.
Overall, pertuzumab with trastuzumab and an aromatase inhibitor, with or without taxane induction, was found to be effective and no new safety signals were identified.