Pertuzumab, Trastuzumab, Plus Aromatase Inhibitor Beneficial in Metastatic Breast Cancer




PERTAIN met its primary progression-free survival objective, showing that pertuzumab plus trastuzumab plus an aromatase inhibitor was superior to trastuzumab plus aromatase inhibitor.
— Grazia Arpino, MD, PhD

In the phase II PERTAIN study of locally advanced or metastatic hormone receptor–positive, HER2-positive breast cancer patients, the addition of pertuzumab (Perjeta) to a regimen of trastuzumab (Herceptin) and an aromatase inhibitor in the first-line setting significantly improved progression-free survival by 3 months. The study was reported at the 2016 San Antonio Breast Cancer Symposium by Grazia Arpino, MD, PhD, of the University of Naples Federico II in Italy.1

“PERTAIN met its primary progression-free survival objective, showing that pertuzumab plus trastuzumab plus an aromatase inhibitor was superior to trastuzumab plus aromatase inhibitor,” she said. Secondary efficacy endpoints and subgroup analyses were generally consistent with the primary analysis.

Dr. Arpino noted that the optimal treatment of metastatic breast cancer that is both hormone receptor–positive and HER2-positive remains an open question. “Bidirectional cross talk” between the estrogen receptor and HER2 leads to resistance to hormonal and anti-HER2 therapies. The standard of care is two anti-HER2 agents plus chemotherapy. The idea of replacing chemotherapy with an aromatase inhibitor has been intriguing.

The rationale for combining pertuzumab, trastuzumab, and an aromatase inhibitor came from the TAnDEM study, where the addition of trastuzumab to anastrozole significantly improved progression-free survival over anastrozole alone,2 and the ­CLEOPATRA study, where the addition of pertuzumab to trastuzumab plus docetaxel significantly improved progression-free and overall survival.3

“We thought pertuzumab plus trastuzumab plus an aromatase inhibitor could, therefore, offer additional benefits,” Dr. Arpino said.

Study Details

The PERTAIN study enrolled 258 women with HER2-positive, hormone receptor–positive locally advanced or metastatic breast cancer not previously treated with systemic nonhormonal therapy in the advanced-disease setting. Patients received trastuzumab (with or without a taxane for 18–24 weeks) plus an aromatase inhibitor (anastrozole or letrozole), or trastuzumab (with or without a taxane for 18–24 weeks) plus pertuzumab and an aromatase inhibitor.

Pertuzumab, Trastuzumab, Aromatase Inhibitor

  • The phase II PERTAIN study evaluated the benefit of adding pertuzumab to trastuzumab plus an aromatase inhibitor in women with locally advanced or metastatic hormone receptor–positive, HER2-positive breast cancer.
  • Compared to trastuzumab plus endocrine therapy alone, the addition of pertuzumab yielded a statistically significant 3-month prolongation of progression-free survival and more durable responses.
  • Median progression-free survival was 18.9 vs 15.8 months (HR = 0.65,
    P = .0070).

The triplet resulted in a median progression-free survival of 18.9 months, compared to 15.8 months for trastuzumab plus an aromatase inhibitor (hazard ratio [HR] = 0.65, P = .0070). The pertuzumab arm was favored in all subgroups, including patients who received induction chemotherapy (HR = 0.75) and those who did not (HR = 0.55). A favorable impact was also seen in all baseline subgroups, she reported.

The overall response rate in the intent-to-treat population was not significantly different: 63.3% for pertuzumab/trastuzumab/aromatase inhibitor (7.3% complete responses), compared to 55.7% (0.9% complete responses) in the control arm (P = .2537). However, the duration of response was significantly longer with the triplet: 27.1 vs 15.1 months (HR = 0.57, P = .0181).

Toxicity Findings

Grade 3 to 4 adverse events were more common in the three-drug arm: 50.4% vs 38.7%. Serious events were observed in 33.1% vs 19.4%, respectively. In the triplet arm, 13 patients discontinued pertuzumab due to toxicity, and 34 required treatment interruptions. The most common toxicities were diarrhea, alopecia, and nausea. In regard to cardiac safety, findings were encouraging; left-ventricular ejection fraction remained above 45% in approximately 90% of patients.

Though some increases in toxicity were observed, Dr. Arpino considered the triplet to be “generally well tolerated” and said no new safety signals arose. ■

Disclosure: Dr. Arpino has financial relationships with Celgene, Amgen, Novartis, Roche, GlaxoSmithKline, and Eisai.

References

1. 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. 2016 San Antonio Breast Cancer Symposium. Abstract S3-04. Presented December 8, 2016.

2. Kaufman B, Mackey JR, Clemens MR, et al: Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: Results from the randomized phase III TAnDEM study. J Clin Oncol 27:5529-5537, 2009.

3. Swain SM, Baselga J, Kim SB, et al: Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372:724-734, 2015.


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