Immediate Impact Anticipated From Neoadjuvant Pertuzumab

Ben Leach
Published: Wednesday, Nov 27, 2013
Neal D. Shore

Dietmar Berger, MD

 

Vice President
Clinical Oncology
Genentech
South San Francisco, CA

The new indication for pertuzumab (Perjeta) as part of a three-drug neoadjuvant regimen for patients with HER2-positive metastatic breast cancer marks the first time the FDA has authorized a therapy based on pathologic complete response (pCR). The next step for the regimen is a phase III trial that is expected to generate additional efficacy and safety data in 2016.

The FDA approved pertuzumab in combination with trastuzumab (Herceptin) and docetaxel on September 30 under its accelerated drug development program based on the findings of several clinical trials, particularly the NeoSphere trial (Table 1).1 Specifically, the regimen is intended for women with HER2-positive, locally advanced, inflammatory, or early-stage tumors (>2 cm or node-positive). Pertuzumab initially was approved in June 2012 in certain HER2-positive metastatic breast cancer settings.

Now, the regimen will be evaluated in the APHINITY study, which has randomized approximately 4800 patients who have undergone surgery for HER2- positive primary breast cancer to trastuzumab plus chemotherapy with or without pertuzumab (Table 2).2 The primary endpoint is invasive disease-free survival.

In an interview with OncologyLive, Dietmar Berger, MD, vice president of Clinical Oncology at Genentech, which developed both pertuzumab and trastuzumab, discusses the reasons that this approval could be important to breast cancer patients, and how it might affect the FDA’s processes.

Table 1. Key Results From NeoSphere Trial1

Endpoint/ Study Population H + T Ptz + H + T Ptz + H Ptz + T
Overall ITT N = 107 N = 107 N = 107 N = 96
pCR,a n (%) [95% CI] 23 (21.5%) [14.1- 30.5] 42 (39.3%) [30.0-49.2] 12 (11.2%) [5.9-18.8] 17 (17.7%) [10.7-26.8]
P value   .0063 (vs H + T) .0223 (vs H + T) .0018 (vs Ptz + H + T)

H indicates trastuzumab; ITT, intent to treat; pCR, pathologic complete response; Ptz, pertuzumab; T, docetaxel.
apCR is defined as absence of invasive cancer in the breast and nodes.

OncologyLive: How will the new pertuzumab regimen fit into the treatment timeline, and what impact will this new option have on patients?

Berger: Patients receive a complete regimen in early breast cancer, which may consist of neoadjuvant treatment, surgery, adjuvant therapy, and perhaps radiotherapy and antihormonal therapy. We are improving that neoadjuvant component. We are helping patients achieve a higher rate of pCR, which we believe also has an impact on long-term outcomes such as disease- free survival or overall survival.

In addition, we can get a promising medicine like Perjeta to patients with early breast cancer faster. Classically, we had to do these studies in the adjuvant setting with a very long time to readout. If you think about classic comparisons, Herceptin took eight years from the metastatic approval to the early breast cancer approval. Now, we would be down to less than two years, and that is really good news for patients.

Table 2. APHINITY Trial2

Patient Population (N= 4800) Experimental Arm Comparator Arm
Operable, HER2- positive primary breast cancer
  • Pertuzumab (840 mg in cycle 1; 420 mg every 3 wk, 52 wk
  • Trastuzumab (8 mg/kg in cycle 1; 6 mg/kg every 3 wk, 52 wk)
  • Standard chemotherapy 6-8 cycles, nonanthracycline or anthracycline-based
  • Placebo (IV every 3 wk, 52 wk)
  • Trastuzumab (8 mg/kg in cycle 1; 6 mg/kg every 3 wk, 52 wk)
  • Standard chemotherapy 6-8 cycles, nonanthracycline or anthracycline-based
Does a higher pCR rate translate into long-term benefits for patients?


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