Just three months ago, Roche Holding was excited about the positive results of its APHINITY clinical trial, designed to test the efficacy of its new breast cancer combination therapy.
Released March 2, the results showed patients with an aggressive type of early breast cancer, called HER2-positive, had fewer chances of disease recurrence or death when they were given a combination of Perjeta, Herceptin, and chemotherapy.
The APHINITY trial compared the efficacy of the drug cocktail against a treatment with Herceptin and chemo alone — both therapies administered after surgery for tumor removal — and found the former was more successful.
Now, the results of the Phase III APHINITY study are in, and — although still positive — they show the combination therapy beats the old Herceptin plus chemo cancer treatment by just about 1 percentage point of improvement.
Perjeta, Herceptin, And Chemotherapy Combination Treatment
Nearly a third of HER2-positive patients suffer a relapse after a successful initial therapy.
To reduce the risk of tumors coming back, women with this form of breast cancer are typically given a year-long therapy course of Herceptin (or trastuzumab) and chemotherapy.
This standard treatment has helped keep cancer from returning in more than 80 percent of these patients.
However, Roche is losing patent protection for Herceptin, which was approved in 1998, and could soon be facing competition — particularly from Puma Biotechnology, a small company that has developed a rival drug called neratinib.
The goal of the APHINITY trial was to show that adding Roche's new breast cancer drug — Perjeta, or pertuzumab — to the treatment would significantly improve survival rates for HER2-positive patients and help extend their lives.
Phase III APHINITY Trial Results
According to the latest results, adjuvant (or after surgery) treatment with Perjeta, Herceptin, and chemotherapy reduced the risk of tumor recurrence or death by 19 percent in patients with HER2-positive early breast cancer, compared with Herceptin and chemo alone.
The Phase III APHINITY trial involved 4,805 patients, who were randomly assigned to receive a year of either Perjeta or placebo in addition to Herceptin and chemo.
Three years after, 94.1 percent of patients treated with the Perjeta combination therapy didn't have their breast cancer return, compared with 93.2 percent treated with Herceptin and chemo alone.
"The goal of adjuvant treatment is to help each person with cancer have the best chance of a cure, and we come closer to this goal with each advance," said Dr. Sandra Horning, Roche's chief medical officer, in a company news release.
"In the APHINITY study, the Perjeta-based regimen improved upon the high bar set by Herceptin in people with HER2-positive early breast cancer," she added.
The results suggest that the benefits of the combination therapy seem to increase over time. An estimate done at four years showed 92.3 percent of patients receiving the drug cocktail remained cancer-free. By comparison, only 90.6 percent of people treated with Herceptin and chemotherapy didn't experience tumor recurrence.
Researchers predict these benefits will become even more significant after the completion of the study, which will follow these patients for a period of up to 10 years.
The results of the Phase III APHINITY trial, published June 5 in The New England Journal of Medicine, were presented the same day at the annual meeting of the American Society of Clinical Oncology.
Why The Perjeta Trial Results Are 'A Disappointment'
The data from the trial shows irrefutable positive results. Yet these results are not as impressive as Roche and the medical community hoped, and come as a blow for the Swiss pharmaceutical company.
Kathy D. Miller, an oncologist at the University of Nebraska, argues the benefits of Roche's breast cancer combination therapy are in fact small, and that they might be outweighed by the drug cocktail's side effects — which include cardiac problems, such as reduced heart function and congestive heart failure.
"To be clear, APHINITY is a positive trial. To be equally clear, as compared with results of studies of pertuzumab in the context of metastatic disease and neoadjuvant therapy, APHINITY is a disappointment," Miller wrote in an editorial featured by The New England Journal of Medicine along with the study.
Although research indicates many people would be willing to endure side effects to see their risk of cancer recurrence reduced by even 1 percent, these results may not be enough to convince the majority of patients to switch over to Roche's pricey new combo therapy.
Adding Perjeta to the current Herceptin plus chemo treatment could double the monthly cost of therapy, which is already priced at $6,100 a month. A year's treatment with Herceptin alone costs $75,000, whereas the combination of Perjeta and Herceptin has a list price of $158,000.
In view of the combo therapy's steep price, its small benefits and its side effects, many patients might choose a year-long treatment course with neratinib instead of taking Perjeta on top of the existing chemotherapy.
Had Perjeta fared much better in the trial, the combination therapy might have hurt the chances for neratinib, which can cause frequent diarrhea.