Hormonal Therapy Effectively Added to Dual HER2-Blockade in Phase II PERTAIN Study

Grazia Arpino, MD, PhD

The addition of an aromatase inhibitor (AI) to pertuzumab (Perjeta) and trastuzumab (Herceptin) improved progression-free survival (PFS) by 3.09 months, when compared with trastuzumab plus an AI, according to findings from the phase II PERTAIN trial presented at the 2016 San Antonio Breast Cancer Symposium.

In the ongoing, open-label study, the median PFS was 18.89 months with the pertuzumab combination compared with 15.80 months for trastuzumab and an AI alone. Furthermore, there was a 35% reduction in the risk of progression or death with the addition of pertuzumab (HR, 0.65; 95% CI, 0.48-0.89; P = .007).

"PERTAIN met its primary PFS objective," said lead investigator Grazia Arpino, MD, PhD, from Rimawi M Università degli Studi di Napoli Federico II, Naples, Italy. "Pertuzumab, trastuzumab, plus an AI was superior to trastuzumab plus AI in postmenopausal women with HER2-positive/HR-positive locally advanced or metastatic breast cancer."

The PERTAIN trial enrolled 258 postmenopausal women with HER2-positive, HR-positive locally advanced or metastatic breast cancer. Patients were randomized to receive pertuzumab with trastuzumab (Arm A; n = 129) or trastuzumab (Arm B; n = 129) alone in combination with an AI with or without induction chemotherapy.

Pertuzumab was administered at a loading dose of 840 mg followed by 420 mg every 3 weeks. Trastuzumab was administered at 8 mg/kg followed by 6 mg/kg every 3 week. AI therapy consisted of either anastrozole at 1 mg daily or letrozole at 2.5 mg daily. All enrolled patients had not received prior treatment with systemic non-hormonal therapy in the advanced setting, and their characteristics were balanced between the arms. Overall, 109 patients in the pertuzumab group and 106 in the trastuzumab/AI alone arm had measurable disease.

In patients with measurable disease, the objective response rate (ORR) with pertuzumab, trastuzumab, and an AI was 63.3% compared with 55.7% for trastuzumab and an AI alone (95% CI, -6.0 to 21.3; P = .02537). “Subgroup analyses were generally consistent with the primary analysis,” said Arpino.

The complete response (CR) rate with pertuzumab was 7.3% and 56% of patients had a partial response (PR). In the trastuzumab arm, the CR rate was 0.9% and the PR rate was 54.7%. At the analysis 26.6% and 27.4% of patients had stable disease (SD), with and without pertuzumab, respectively. The disease control rate (CR + PR + SD) was 89.9% with pertuzumab compared with 83% without. More patients experienced progressive disease in the absence of pertuzumab (5.5% vs 12.3%).

The median duration of response was 27.10 months with the pertuzumab combination compared with 15.11 months for trastuzumab and an AI alone. This represented a near doubling in the duration of response between the two arms (HR, 0.57; 95% CI, 0.36-0.91; P = .0181).

Adverse events (AEs) of all-grades regardless of cause occurred in 96.1% of patients treated with pertuzumab compared with 98.4% in the trastuzumab arm. Grade ≥3 AEs were seen in 50.4% of those treated with pertuzumab versus 38.7%. The most common grade ≥3 AEs in the pertuzumab combination group and trastuzumab alone group, respectively, were hypertension (10.2% vs 11.3%), diarrhea (7.1% vs 2.4%), and neutropenia (3.1% vs 6.5%).

"Pertuzumab, trastuzumab, and an AI was well tolerated and no new safety signals were identified," Arpino noted.

A phase III study, initiated in Germany, is comparing chemotherapy versus endocrine therapy in combination with dual HER2-targeted therapy with trastuzumab and pertuzumab for patients with HER2-positive/HR-positive metastatic breast cancer. This multicenter study is focused on adverse events, with secondary endpoints assessing efficacy. The estimated completion date for the study September 2021 (NCT02344472).

Arpino G, Ferrero J-M, 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. Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10; San Antonio, TX. Abstract S3-04.

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Based on investigator's discretion, induction chemotherapy could be given for 18 to 24 weeks prior to starting endocrine therapy. Induction consisted of either docetaxel every 3 weeks or paclitaxel weekly. In the pertuzumab arm, 32.6% of patients received docetaxel and 24.8% got paclitaxel. In the trastuzumab arm, 28.7% received docetaxel and 24% got paclitaxel.