The target of extensive study has been the role of bidirectional cross talk between the human epidermal growth factor receptor 2 (HER2) and estrogen receptors in resistance to endocrine therapy and anti-HER2.1,2 PERTAIN was the first randomized phase 2 trial that evaluated the addition of pertuzumab to trastuzumab plus an aromatase inhibitor with or without induction chemotherapy for the first-line treatment of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer or locally advanced breast cancer.
At a median follow-up of 31 months, PERTAIN met its primary progression-free survival end point, with a possible enhanced effect in certain groups (eg, in patients who had not received induction chemotherapy).3 The final analysis was conducted by Gazia Arpino of University Federico II, Naples, Italy, and colleagues and represents data over 6 years, including the latest findings on mature overall survival (secondary end point), progression-free survival, and updated safety data.
Using 1:1 randomization, a total of 190 patients received either pertuzumab plus trastuzumab and an aromatase inhibitor (arm A) or trastuzumab and an aromatase inhibitor (arm B). Given initially as an 840-mg intravenous (IV) loading dose, pertuzumab was followed by 420 mg every 3 weeks; trastuzumab IV, at 8 mg/kg followed by 6 mg/kg every 3 weeks; anastrozole, at 1 mg daily; or letrozole, at 2.5 mg daily. At the investigator’s discretion, before the start of endocrine therapy, induction chemotherapy with docetaxel every 3 weeks or weekly paclitaxel could be given for 18 to 24 weeks. Patients received treatment until disease progression or unacceptable toxicity.
Notably, the median progression-free survival in the group of patients who received no induction chemotherapy was 27 months in arm A and 12 months in arm B. However, with induction chemotherapy, the median progression-free survival was 17 months for both treatment arms. Furthermore, when comparing median overall survival with no induction, there was a considerable difference between arm A (65 months) and arm B (54 months).
Adverse events were reported in 122 patients per arm. The incidence of grade ≥3 adverse events was 56.7% and 41.1% in arms A and B, respectively. The most common grade ≥3 adverse events reported in ≥5% of patients in arm A versus arm B was hypertension (11.8% vs 10.5%), diarrhea (9.4% vs 2.4%), and neutropenia (3.1% vs 7.3%).
The authors concluded that the progression-free survival benefit of pertuzumab to hormone therapy plus an aromatase inhibitor was maintained, with a median follow-up of >6 years at final analysis. There was similarity of overall survival between arms. An enhanced treatment effect was potentially observed in patients through the addition of pertuzumab to hormone therapy plus an aromatase inhibitor who had not received induction chemotherapy after randomization. At final analysis, there were no new safety concerns. This study highlights that select patients may receive benefit from this combination, without induction chemotherapy.
Source: Arpino G, de la Haba-Rodriguez J, Ferrero JM, et al. Final analysis of PERTAIN: a randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD3-02.
Learn more about our family of publications.
View Our Publications