September 9th, 2013 - There have to be better ways to figure out whether or not a cancer medicine works, and get new treatments into the hands of patients. If we collaborate, can we fix some of these problems? This week in D.C., cancer experts, patient advocates, the FDA and Genentech will meet to discuss whether using a new measure of a medicine’s effectiveness in breast cancer, called “pCR,” could be one solution.
Challenges with the Current Model
To determine whether a cancer medicine works in clinical trials, doctors typically use measurements called endpoints. An endpoint is exactly as it sounds: an event or outcome that can be measured objectively to determine whether the medicine being studied is helping patients.
One of the most common endpoints used when developing any new cancer medicine is whether it helps people live longer. This measure, called “overall survival,” is an extremely meaningful one, yet it has its challenges. One of the biggest is the length of time it takes to evaluate. For example, in some diseases (like blood and breast cancers) it can take between five and 10 years to show an improvement in overall survival. This significantly prolongs the time needed to measure the medicine’s effectiveness and delays delivery of the medicine to patients.
Is There a Better Way?
But times are changing. Using new clinical trial endpoints and advances in technology, we can assess much earlier whether a medicine is working. However, before one of these new endpoints can be used to support the approval of a new medicine, the FDA must determine if the endpoint can predict the long-term effectiveness of the medicine. That is, can we reliably measure today that a medicine will provide a benefit to patients far in the future?
More info on endpoints: If a new clinical trial endpoint is proven to predict a long-term benefit, the endpoint may be called a surrogate endpoint. There has been ongoing debate about surrogate endpoints in the cancer community, for example around the potential use of minimal residual disease (MRD) to predict long-term benefit in blood cancers and progression-free survival (PFS) to predict survival in solid tumors.
A New Approval Pathway, Using pCR
A newer endpoint, which is commonly used in breast cancer, is called pathological complete response (pCR). pCR is used to measure the effectiveness of a medicine given prior to surgery (this is known as the “neoadjuvant treatment” setting) in someone with early breast cancer. Early breast cancer means a person’s cancer has not spread to other parts of the body. If a person taking a specific medicine has a pCR after neoadjuvant treatment, it means there is no remaining cancer tissue detectable at the time that person has surgery (Note: surgery is still needed to examine the tissue from the tumor site and ensure there are no remaining cancer cells).
So, measuring whether or not a person had a pCR (reminder: no cancer tissue detectable at the time of surgery) as a result of treatment can be assessed more quickly than traditional endpoints in early breast cancer – in some cases, in a matter of weeks.
The FDA has stated there is a significant need to bring new medicines to people with certain types of high-risk early breast cancer. To help address this need, the FDA issued a draft guidance last year on the use of pCR as a potential endpoint to support accelerated approval of new medicines in high-risk early breast cancer.
This week’s D.C. meeting will shed light on whether this new FDA pathway, designed to bring promising medicines to people with early breast cancer more quickly, can possibly be put into practice. Part of this discussion will focus on pCR as a proposed surrogate endpoint for predicting long-term benefit.
Worth knowing: An FDA meta-analysis of nearly 12,000 people with early breast cancer found that individual patients who achieved a pCR had improved long-term event-free survival (EFS, the time a person lives without a cancer-related “event” such as their disease getting worse) and overall survival (OS, or how long a person lives). However, the meta-analysis was unable to demonstrate that pCR is an established surrogate for EFS or OS.
Treating Early Matters
If we can shorten the timeframe it takes to determine whether a breast cancer medicine works, that is clearly good news for patients. But here is some more good news: a person diagnosed with breast cancer in its earliest stages, before it has spread, has the potential for a cure.
The bad news is existing medicines still don’t work for everyone; approximately 40,000 people die of breast cancer in the United States each year. Accelerating drug development in high-risk early breast cancer could save thousands of lives each year.
As a former practicing oncologist, I find it very difficult to wait several years for a new medicine to be available for people who might need it. What’s more, I know that the FDA, and especially people with cancer and their families, share this view. That’s why I hope the use of new endpoints like pCR, and other important new pathways like Breakthrough Designation, can help bring new medicines to people with cancer more quickly.
It’s critical that we all strive to identify new clinical trial endpoints and technologies that could accelerate drug development across all types of cancer. And Genentech is pleased to be part of these important discussions.