Swain Discusses Final Survival Analysis of CLEOPATRA Study

For additional insight on the CLEOPATRA trial and its implications for clinical practice, OncLive interviewed Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at MedStar Washington Hospital Center.

Sandra Swain, MD

Results from the phase III CLEOPATRA study showed the addition of pertuzumab (Perjeta) to trastuzumab (Herceptin) and docetaxel (Taxotere) as a first-line therapy for metastatic HER2-positive breast cancer improved overall survival by nearly 16 months versus trastuzumab plus docetaxel.

In the double-blind trial, the addition of pertuzumab was associated with a 32% reduction in both the risk of death and the risk of disease progression.

The final survival data, which were initially reported at the 2014 ESMO Congress, have now been published in The New England Journal of Medicine.

For additional insight on the CLEOPATRA trial and its implications for clinical practice, OncLive interviewed Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at MedStar Washington Hospital Center. Swain was the lead author on the study and presented the updated survival results at the 2014 ESMO Congress.

OncLive: Please provide some background on the CLEOPATRA trial.

Dr Swain: The CLEOPATRA study was started in 2008 and culminated in 2010, and it is a study that included patients with HER2-positive advanced breast cancer who had never had treatment for advanced disease. The study was a randomized study and the patients were randomized between Taxotere, Herceptin, and Perjeta, and Taxotere, Herceptin, and placebo.

What was seen in this final overall survival analysis?

So the question was, did Perjeta add to the outcome for the patients in the study? And it did.

There were 808 patients in the study, and it was a multinational study. The patients who received Perjeta lived 16 months longer than those who didn’t. But more importantly, the median survival for the Perjeta group was 56.5 months, so it’s very long. And we’ve never really seen this kind of survival in such an aggressive form of breast cancer before.

What are the main side effects associated with this pertuzumab regimen?

The main side effects were diarrhea, rash and then also fever with a low white blood cell count.

What does a community oncologist need to know about these results?

I think they need to know that every patient who has advanced HER2-positive breast cancer should be given this combination of Perjeta and Herceptin with chemotherapy upfront, and they usually are treated with a chemotherapy for 4 to 6 months and then that stops, and then they continue to receive the targeted therapy—the Perjeta and Herceptin—as long as they’re still doing well.

These are the updated survival results for the CLEOPATRA study. The drug was initially approved in 2012 based on the PFS outcomes from the trial. How will these new data change clinical practice?

Yes, when the first results were presented with the progression-free survival endpoint a couple of years ago, Perjeta was approved by the FDA, so this is the final analysis. I think what will change is instead of [just] a large number of patients are actually getting it, I think every patient is now going to have the opportunity to get it, because you can’t really argue with those kind of survival results. And when physicians see that, I’m sure they’ll definitely want to give their patients this combination.

What remaining questions need to be answered?

One question is, “can we use it earlier in disease?” For example, stage I or II disease. And that is a question that was asked in the APHINITY trial, with a similar kind of randomization. It was chemotherapy, Perjeta, and Herceptin compared with chemotherapy, placebo, and Herceptin, and that’s completed but the results aren’t out yet. If that’s positive, I think every patient with HER2-positive disease upfront will be getting this.

Were you surprised by the results of the MARIANNE, which the combination of T-DM1 plus pertuzumab?

Yes, I was surprised. I think we all expected and hoped that T-DM1 and pertuzumab would be superior to the standard treatment with Herceptin and chemo but it wasn’t. So, that is disappointing. However, pertuzumab is now looking like it’s a much better drug and, especially combined with Herceptin, seems to be really the treatment of choice.

Is there anything else about this final CLEOPATRA analysis that you would like to mention?

I think the exciting thing is that the patients are living much longer, and even if in the advanced stage they eventually have progression of their disease, there’s many, many, more studies ongoing, looking at trying to improve [outcomes], and every day new developments are coming up.

And the other thing, too, that I think is really important for patients, is because these women went on this clinical trial, now we have this great result. Clinical trials are really important, especially when you have an opportunity to have something that’s better. You don’t know that when you go in a trial, but certainly you get standard of care and then the possibility of getting better than that. So I think considering a clinical trial is really important.


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