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
Authors: Arpino Grazia , de la Haba-Rodriguez Juan , Ferrero Jean-Marc , De Placido Sabino , Klingbiel Dirk , Revelant Valentine , Wohlfarth Christine , Poppe Raf , Rimawi Mothaffar F 
Published: February 2021

Abstract
Background The role of bidirectional cross talk between the HER2 and estrogen receptors in resistance to anti-HER2 and endocrine therapy has been studied extensively (Kaufman et al. J Clin Oncol 2009; Arpino et al. J Natl Cancer Inst 2007). The CLEOPATRA study showed that first-line pertuzumab (P) + trastuzumab (H) + docetaxel (T) improved progression-free survival (PFS) and overall survival (OS) significantly compared with placebo + H + T in patients (pts) with HER2-positive metastatic BC (MBC) (Baselga et al. N Engl J Med 2012; Swain et al. Lancet Oncol 2013; N Engl J Med 2015; N Engl J Med 2020). PERTAIN (NCT01491737) was the first randomized phase II trial to assess the addition of P to H + an aromatase inhibitor (AI) ± induction chemotherapy for the first-line treatment of pts with HER2-positive and hormone receptor-positive MBC or locally advanced BC (LABC). PERTAIN met its primary PFS endpoint at 31 months’ median follow-up, with a potentially enhanced effect in some groups, such as pts who did not receive induction chemotherapy (Rimawi et al. J Clin Oncol 2018). We present the final analysis at more than 6 years’ median follow-up, including updated PFS, mature OS (secondary endpoint), and updated safety. Methods Pts were randomized 1:1 to P + H + AI (Arm A) or H + AI (Arm B). P was given as an 840 mg intravenous (IV) loading dose followed by 420 mg every 3 weeks (q3w); H IV, at 8 mg/kg followed by 6 mg/kg q3w; anastrozole, at 1 mg daily; or letrozole, at 2.5 mg daily. Induction IV chemotherapy with T q3w or weekly paclitaxel could be given for 18-24 weeks at the investigator’s discretion before the start of endocrine therapy. Treatment was given until disease progression or unacceptable toxicity. Pts were stratified by induction chemotherapy (yes/no) and time since adjuvant hormone therapy (&lt;12 months, ≥12 months, no adjuvant hormone therapy). Time-to-event endpoints were analyzed using Kaplan-Meier methods. Results Pts were randomized across 71 sites and 8 countries between Feb 2012 and Oct 2014. Intent-to-treat populations were 129 pts per arm; safety populations, 127 and 124 in Arms A and B, respectively; induction chemotherapy was received by 75 and 71 pts, respectively. Baseline demographics and disease characteristics were generally balanced between arms. Efficacy results are shown in the table. One hundred twenty-two pts per arm reported adverse events (AEs) at any grade (96.1% in Arm A; 98.4% in Arm B); 72 (56.7%) and 51 pts (41.1%) had grade ≥3 AEs, the most common grade ≥3 AEs (≥5.0%; Arm A vs. Arm B) being hypertension (11.8% vs. 10.5%), diarrhea (9.4% vs. 2.4%), and neutropenia (3.1% vs. 7.3%).
Conclusions With a median follow-up of more than 6 years at final analysis, the PFS benefit of adding P to H + an AI was maintained. OS was similar between arms. A potentially enhanced treatment effect was observed by addition of P to H + an AI in pts who did not receive induction chemotherapy after randomization. There were no new safety concerns at final analysis. Overall, PERTAIN provides additional evidence on the role of P + H in the first-line treatment of HER2-positive MBC/LABC and suggests that some pts benefit from P + H + AI without induction chemotherapy.
Arm AArm BMedian PFS, mo HR (95% CI)ITT21160.7 (0.5-0.9) p=0.006With induction17170.7 (0.5-1.0) p=0.08No induction27120.7 (0.4-1.0) p=0.07Median OS, mo HR (95% CI)ITT60571.1 (0.7-1.5) p=0.8With induction59661.2 (0.7-1.9) p=0.5No induction65540.9 (0.5-1.6) p=0.7CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; mo, months.
Citation Format: Grazia Arpino, Juan de la Haba-Rodriguez, Jean-Marc Ferrero, Sabino De Placido, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi. 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 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-02.