Sign of Progress at the FDA?
NBCC has long pushed for drug approvals based on clinically-significant outcomes: meaningful improvements in length of life or quality of life. And yet, over the last 20 years, we have seen a number of new drugs come to market for breast cancer based solely on evidence from surrogate outcomes (e.g., progression-free survival [PFS]) with little-to-no evidence of improved clinical benefit for patients, but with evidence of harm. On February 9, 2021, the U.S. Food and Drug Administration (FDA) convened the Oncologic Drugs Advisory Committee (ODAC) to consider a requested accelerated approval for the immune checkpoint inhibitor pembrolizumab (Keytruda®) for early, high-risk triple-negative breast cancer (TNBC). The request was based on early data from the ongoing KEYNOTE-522 clinical trial. Note, this drug received “accelerated approval” for use in PD-L1 positive metastatic and advanced TNBC on November 13, 2020. That approval was based on a 4.1 month improvement in PFS (9.7 vs. 5.6 months) for patients whose tumors express PD-L1 [CPS ≥ 10] treated with pembrolizumab and chemotherapy vs. chemotherapy alone. No data have yet been presented regarding overall survival, a co-primary endpoint.
NBCC applauds the FDA and ODAC for deferring a decision on approval until further data are available.[2]
The FDA analysis provided to ODAC emphasized the ongoing trial’s immature and unreliable survival data. It further noted that “neoadjuvant pembrolizumab confers only a small absolute improvement in pCR (pathologic complete response) rate which is of questionable clinical meaningfulness.” More importantly, the Agency recognized that the addition of pembrolizumab to standard therapy appears to increase toxicity due to increased immune-mediated adverse events (e.g., death in ~1% of patients), some of which are severe, irreversible, and/or require life-long medication in potentially curable and otherwise healthy patients.
NBCC commends this decision, and we hope it signals a change in the level of evidence required before bringing drugs of considerable cost to market for patients in desperate need of real progress.
Breast Cancer Mortality Rates in Younger Women: Reading Beyond the Headlines
There have been a number of news pieces circulating about the possibility that breast cancer mortality rates in younger women are going up. See, e.g., “Breast cancer death rates have risen slightly for women in their 20s and 30s,” published in the Washington Post, Saturday, Feb. 13, 2021.) These news articles followed the publication of a study that was published on Feb. 9, 2021 by Hendrick et al., in Radiology.
The study results are not quite what the news articles report.
Of course, the information must be analyzed in the context that breast cancer in younger women is uncommon. As a point of reference, according to the American Cancer Society (ACS), in 2020, approximately 268,600 women were diagnosed with invasive breast cancers, 4 percent of which were in women under the age of 40, with the median age of diagnosis of 62 years of age. Approximately 2.6% of the roughly 43,000 deaths from breast cancer that are expected to occur in 2021 will be in women in women 20 to 39 years of age, with 23.2 percent in women between 40 and 59 years, and 74.2 percent in women 60 years and older.
While NBCC believes that any deaths from breast cancer are too many, it is important to have an accurate assessment of the problem. Is the mortality rate in younger women with breast cancer actually rising?
Hendrick et al., showed that annual deaths from breast cancer were declining for women 20 to 39 from ~1990 to 2010 (and for women 40 years and older through 2017), likely the result of improved treatments. However, their analysis also showed that between 2010 to 2017 deaths from breast cancer had plateaued for women 20 to 39 years age, with no significant increase in the mortality rate for this age group, which is holding steady at about 2.75 to 3 per 100,000 women.
There are a number of possible reasons for the mortality plateau in younger women, one of which is that women who develop breast cancer early in life typically are diagnosed with more aggressive cancers for which there are no targeted treatments and that have a worse prognosis (e.g., triple-negative breast cancer). The reaction to these data is often to expand screening in this age group. However, the scientific evidence does not support that response. Lowering the age at which universal screening begins, which is what many see as the take-away message from this article, is not a solution. Indeed, according to a comprehensive analysis[1] conducted by the United States Preventive Services Task Force, screening does not reduce all-cause mortality (the primary goal of screening) in any age group, and only minimally reduces breast cancer mortality for women between the ages of 50 and 69.
All deaths from breast cancer are unacceptable, and that is why NBCC trains its advocates to critically analyze information so that policy approaches to ending breast cancer are meaningful.
Register Today and Join Us at the NBCC Virtual Advocate Leadership Summit
Join with fellow survivors, advocates, and members of the breast cancer community, who are lending their voice and transforming breast cancer research and public policy, and ensuring quality healthcare for all.
Exciting plenaries and skill-building workshops will focus on the most critical areas of breast cancer research, science, and public policy.
Attendees will have opportunities to network with other breast cancer survivors and advocates, and connect with leading researchers in the field.
Our annual Lobby Day will follow the Summit on May 18, when advocates will meet with their elected officials under the leadership of NBCC, about our 2021 legislative and public policy agenda. Lobby Day briefing and other related sessions will be held May 17.
The registration fee is $150 and entitles you to:
What’s Your NBCC Advocacy Story?
As we near the NBCC Advocate Leadership Summit and Lobby Day, we want to hear from advocates because, without you, our work to end breast cancer is not possible.
Share your story with us! We want to share your advocacy story with others so they, too, can become a catalyst in our fight to end breast cancer.
Join the President’s Council
Every second counts in our efforts to achieve the goal of ending breast cancer. And every dollar made equates to more lives saved.
A $1,000 or more gift entitles you to a membership in the President’s Council, an exclusive membership group with special benefits. Members receive regular communications directly from President Fran Visco on current breast cancer issues, recognition in publications, and invitations to special events. Your gift is more than a contribution. It is an investment that will enable us to end breast cancer, once and for all. Donate today.
NBCC Moved Offices!
In case you missed our email a week ago, the National Breast Cancer Coalition has officially moved offices in Washington, D.C. Our new address is:
National Breast Cancer Coalition (Fund)
2001 L Street NW, Suite 500 PMB #50111
Washington, DC 20036
Please save this address for any future mailing needs and correspondence with NBCC. We look forward to continuing to serve you from a new location!
[1] Siu AL; U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Feb 16;164(4):279-96. doi: 10.7326/M15-2886. Epub 2016 Jan 12. Erratum in: Ann Intern Med. 2016 Mar 15;164(6):448. PMID: 26757170.
[2] On February 9, 2021, the ODAC voted unanimously that a regulatory decision on pembrolizumab in combination with multi-agent chemotherapy for neoadjuvant treatment followed by pembrolizumab monotherapy for adjuvant treatment of high-risk early-stage TNBC be deferred until further data are available from future analyses of KEYNOTE-522.
