Abstract PD3-02: 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

Background: Preclinical and clinical evidence suggest that cross-talk between HER2 and estrogen receptor signaling pathways in breast cancer (BC) contributes to treatment resistance (Kaufman et al. J Clin Oncol 2009; Arpino et al. J Natl Cancer Inst 2007). First-line pertuzumab (P), in addition to trastuzumab (H) + docetaxel (T), significantly improved progression-free survival (PFS) and overall survival (OS) compared with H + T in patients (pts) with HER2-positive metastatic BC (MBC) (Swain et al. N Engl J Med 2015; Baselga et al. N Engl J Med 2012). PERTAIN (NCT01491737) is the first study to assess first-line P + H + an aromatase inhibitor (AI) ± induction taxane therapy in postmenopausal women with hormone receptor-positive, HER2-positive locally advanced (LA)/MBC. Methods: Pts with HER2-positive, hormone receptor-positive LA/MBC who had not received prior systemic therapy (except endocrine therapy) were randomized 1:1 to Arm A: P + H + AI or Arm B: H + AI. Study medication: P 840 mg loading dose followed by 420 mg every 3 weeks (q3w); H 8 mg/kg followed by 6 mg/kg q3w; anastrozole 1 mg daily (qd) or letrozole 2.5 mg qd. Induction T q3w or paclitaxel (PAC) weekly could be given for 18–24 weeks at the investigator9s 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 ( Results: From February 2012 to October 2014, 129 pts were randomized to Arm A and 129 to Arm B (intent-to-treat populations; safety populations: 127 and 124, respectively) across 80 sites and 8 countries. Baseline demographics and disease characteristics were generally balanced between arms. Induction T and PAC were received by 42 (32.6%) and 32 (24.8%) pts in Arm A, respectively, and 37 (28.7%) and 31 (24.0%) pts in Arm B. Median PFS was 18.9 months in Arm A and 15.8 months in Arm B (HR 0.65; 95% CI 0.48–0.89; p=0.007). 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 pts 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%) pts. The most common grade ≥3 AEs (≥5%; Arm A vs. Arm B) were hypertension (10.2% vs. 11.3%), diarrhea (7.1% vs. 2.4%), and neutropenia (3.1% vs. 6.5%). Conclusions: PERTAIN met its primary endpoint: P + H + AI is effective and well tolerated, and may offer a novel treatment option for pts with HER2-positive/hormone receptor-positive LA/MBC. Citation Format: Arpino G, Ferrero J-M, de la Haba-Rodriguez J, Easton V, Schuhmacher C, Restuccia E, Rimawi M. 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 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S3-04.