Javier Cortés, MD, on the CLEOPATRA Trial

Oncology (Williston Park). 29(10):718.

Javier Cortés, MD

1 Can you talk about the CLEOPATRA trial that was published earlier this year? What was the goal of this study?

The CLEOPATRA trial is a randomized, double-blind, placebo-controlled, international phase III study for patients with HER2-positive metastatic breast cancer. In brief, patients were randomized to receive docetaxel and trastuzumab with either placebo or pertuzumab. The primary endpoint of the trial was progression-free survival (PFS), and over 800 patients were included. At a median follow-up of 50 months, patients who received pertuzumab-based therapy had a median PFS of 18.7 months, compared with 12.4 months for those patients who received placebo-based treatment. The hazard ratio (HR) was 0.68.

2Why was the overall survival benefit observed in this trial so significant?

One of the most amazing results from the CLEOPATRA study was the overall survival (OS) data. Patients who received pertuzumab, trastuzumab, and docetaxel had a median OS of 56.5 months, and those patients who received placebo in combination with trastuzumab and docetaxel had a median OS of 40.8 months (HR, 0.68). So, median OS increased by almost 16 months. This result was clearly unexpected, and the reasons for this significant difference are being studied.

3 Were there any concerning toxicities observed in any of the patients in this trial?

One of the most interesting things regarding pertuzumab-based therapy is that these improvements in outcomes were not associated with a significant increase in toxicity. Diarrhea and febrile neutropenia were the most relevant grade 3/4 adverse events. The rate of grade 3 and 4 diarrhea increased from 5.1% to 9.3% when pertuzumab was administered, and febrile neutropenia from 7.6% to 13.7%. However, the incidence of cardiotoxicity did not change with the addition of pertuzumab. Moreover, the rate of grade 3 or higher left ventricular dysfunction was somewhat lower in the pertuzumab group (3.3% vs 1.5%).

4 Do you consider these practice-changing results, specifically for HER2-positive metastatic breast cancer?

Absolutely. These unprecedented data are, in my opinion, the most significant in the history of metastatic breast cancer research, establishing this combination of pertuzumab, trastuzumab, and chemotherapy as the new standard of care in the first-line treatment setting for patients with HER2-positive metastatic breast cancer.

5Are there any follow-up studies currently planned or in progress?

There are several studies that will help us to define the role of pertuzumab and trastuzumab with different partners. In my opinion, of greatest interest will be the upcoming data of these two monoclonal antibodies in combination with endocrine therapy, and the results of the PHEREXA trial, a randomized study that will define the role of pertuzumab with trastuzumab and capecitabine in patients progressing on trastuzumab-based therapy. In addition, other chemotherapeutic agents are being explored with this dual blockade.

Financial Disclosure: Dr. Cortés receives a consulting fee from Roche and Celgene; and receives an honoraria from Roche, Celgene, Novartis, and Eisai.