SABCS 2020: Patient-centered FDA Approvals

By Tibby Reas Hinderlie, Communications Officer

I joined Breast Cancer Action as the Communications Officer in July of 2020, which makes this year’s San Antonio Breast Cancer Symposium (SABCS) my first breast cancer conference. Given that SABCS is geared towards clinicians and researchers, processing the huge amount of information (1194 abstracts will be presented this year!) on “basic” breast cancer science and treatment protocols can be overwhelming. But it’s important to understand what all this data really means, because it is the basis for evolving standards of care as well as Food and Drug (FDA) approvals.

Luckily, thanks to its 30 year track record, Breast Cancer Action has three core criteria to evaluate drug trials on track for FDA approval. These patient-centered principles can make understanding SABCS sessions easier for first-timers and patient advocates like myself as we dive into the general sessions, where new studies and treatment breakthroughs are presented. And since I’m finding this useful, I want to share with those of you who may be new to these issues as well.

These three guiding principles, and the endpoints used to demonstrate them, are important to Breast Cancer Action because as an independent (free from industry influence), patient-centered, health justice organization, we know that our quality of life and overall survival is how drugs should be evaluated—not how much money these drugs make for pharmaceutical and biotech companies.

More Effective, Less Toxic, More Affordable

Breast Cancer Action’s long-standing position is that in order for a treatment to be approved by the Food and Drug Administration, it should be more effective, less toxic, or more affordable than existing treatments.

This means when listening to a presentation on a treatment breakthrough at SABCS, we are asking ourselves – and often the presenters – these three questions:

  1. Does this treatment extend overall survival?
  2. Does this treatment improve quality of life?
  3. Does this cost less than therapies that are already available?

“Endpoints” are what’s being measured in a particular trial—and they aren’t all equally meaningful. They will be presented as part of the methodology and study design, and common phrases and acronyms include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), objective response rate (ORR) and pathological complete response (pCR). We’ve written on the definitions and differences of each of these endpoints, and when evaluating research on new treatment, we’re keeping an eye out for improvements in overall survival and improvements in quality of life factors, such as a reduction in adverse effects.

In some circumstances, even when a new treatment doesn’t improve overall survival or quality of life, it can still earn a “thumbs up” from Breast Cancer Action in terms of approval, if it is costs less, and therefore more accessible to more people who need it.

The FDA and Accelerated Approvals

Breast Cancer Action believes a new drug should not be given full approval by the FDA until and unless it has been demonstrated to improve overall survival in patients or improve side effects. But currently, many breast cancer drugs are approved through accelerated approvals.

As we saw in Tuesday morning’s “FDA and Breast Cancer Workshop,” the three breast cancer drugs approved by the FDA and discussed during the session, tucatinib (approved in April 2020) sacituzumab (approved in April 2020) and fam-trastuzumab deruxtecan-nxki (approved in December 2019) were each approved through accelerated approvals. Sacituzumab was given breakthrough therapy designation (BTD), fam-trastuzumab deruxtecan-nxki was given breakthrough therapy designation (BTD) as well as Fast Track designation (FTD), and tucatinib was granted Fast Track designation (FTD), Orphan Drug Designation (ODD), and Breakthrough Therapy Designation (BTD) to expedite the approval.

As Dr. Virginia Kaklamani stated in Wednesday morning’s opening remarks, this year “remarkably 6 new breast cancer treatments were approved with clinical trials demonstrating clinically meaningful improvements in overall survival for our patients” (emphasis mine). But this is not always the case. Accelerated approvals can be problematic because they are often not based on the clinical endpoint of overall survival or quality of life, but rather on surrogate endpoints. Surrogate endpoints are indicators that suggest treatments may ultimately be effective, not measures of treatment efficacy. They are easier and cheaper for researchers to study because it takes less data to document tumor shrinkage, or progression-free survival (PFS), compared to survival (OS) which requires larger, longer studies.

Surrogate endpoints are useful for researchers—they are an indicator that a drug trial is working and on track, and tells the researcher to keep going in their work—but they do not prove that drugs actually work! Unfortunately, slowing tumor growth in the short term does not always extend survival, ensuring people live longer.

There are those who argue we can’t afford to wait—we need new treatments now. There are times when someone may choose to take a drug before it’s been proven safe and effective. Arguing for strong patient-centered FDA standards does not stop people from accessing experimental drugs. Patients can still gain access to experimental drugs through clinical trials and the FDA’s “compassionate use” program. But there is an important difference between allowing use of an unproven, experimental drug and granting full approval, which lets companies sell treatments on the open market before they’ve been shown to extend the life or improve the quality of life of the person taking that drug.

Speed, Excitement, and COVID-19

Exciting approval tracks like “Breakthrough Therapy” Designation and “Orphan Drug” Designation sound like they are good for people—don’t we all want medical breakthroughs and treatments for rare diseases? But a flashy label does not guarantee that the treatment works if all we have are surrogate endpoints.

And this year, the excitement for new and cutting-edge drugs is set amongst a backdrop of the global race for fast vaccine approval under COVID-19, and the gratitude from researchers and the general public that we are able to access this drug as soon as possible. During this time, it is crucially important that we uphold patient-centered standards, and not allow the speed of a drug trial to take precedence over efficacy, safety, and accessibility in the approval process. After all, it doesn’t matter how fast it’s approved if it doesn’t work. 

Industry often sets up a false dichotomy between speed and high standards, and we can resist this framing. For many people with breast cancer, caregivers, and advocates, both are important, and we are tired of waiting for new treatments. Many people feel like they are suffering under (and being failed by) the current slash and burn treatment options. But despite our impatience, our priority continues to be treatments that extend survival, improve quality of life, and are accessible to people facing this disease.

As I attend presentations throughout the conference, I’ll be listening for BCAction’s three core tenets of what a new drug needs to earn FDA approval, knowing that putting patient-centered endpoints before the speed of a drug approval is what really matters for people with breast cancer.

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