On March 8, 2019, the US Food and Drug Administration (FDA) approved the PD-L1 inhibitor atezolizumab for first-line treatment of metastatic triple-negative breast cancer in combination with nab-paclitaxel chemotherapy for patients who are ineligible for surgery and whose tumors express PD-L1. This marks the first time a regimen approved for breast cancer includes an immunomodulator, and represents the first targeted agent approval in triple-negative breast cancer — a disease that, historically, has only had chemotherapy as a treatment option.
Triple-negative breast cancer is an especially aggressive subtype of breast cancer that is identified by the absence of expression of estrogen, progesterone, or HER2 protein receptors on the cancer’s surface. These proteins, when present in other subsets of breast cancer, allow us to target and take advantage of the protein to kill the cancer cell. For patients with triple-negative metastatic cancer, the average survival is only slightly more than a year, meaning that half of women diagnosed with this disease will not live beyond that benchmark.
This groundbreaking approval was based on results of the IMpassion130 trial (ClinicalTrials.gov Identifier: NCT02425891), for which Sarah Cannon, the Cancer Institute of HCA Healthcare in Nashville, Tennessee, participated. The IMpassion130 trial treated 902 women with either nab-paclitaxel alone or nab-paclitaxel in combination with atezolizumab.
A post-hoc update of long-term progression-free survival revealed that in the PD-L1 immune cell-positive population, the updated median progression-free survival was 7.5 months
(95% CI, 6.7–9.2) with atezolizumab plus nab-paclitaxel and 5.3 months (95% CI, 3.8–5.6) for nab-paclitaxel alone (stratified hazard ratio [HR], 0.63; 95% CI, 0.50–0.80; P <.0001).1
In patients with PD-L1–positive tumours, median overall survival was 25 months (95% CI, 19.6–30.7) with atezolizumab and 18 months (13.6–20.1) with placebo. The stratified hazard ratio for overall survival was 0.71 (95% CI, 0.54–0.94).1
Immunotherapy treatments help a patient’s immune system recognize cancer as “foreign” and attack it. In contrast to chemotherapy, which can be thought of as poison for cancer cells, immunotherapy is essentially a way to boost one’s own immune cells to fight cancer. Chemotherapy has known side effects, such as hair loss, nausea, and fatigue; however, the side-effect profile for immunotherapy treatment is different. Patients receiving immunotherapy treatment may experience low thyroid hormone levels or inflammation in the lungs or gastrointestinal system. When treating patients with immunotherapy, it is important to closely monitor patients for these rare side effects and treat them with steroids when appropriate.
The approval of atezolizumab not only represents a “win” for some patients with triple-negative breast cancer characterized by PD-L1 expression, it also more broadly represents a win for personalized medicine. In the past decade, we have gotten smarter about knowing that every person’s cancer may be driven by individual mutations and alterations. We have had access to tests to examine the expression of estrogen receptors, progesterone receptors, and HER2 receptors for some time, but only now do we know to test for PD-L1, which allows us break this broad disease down into smaller subsets using the markers the cancer possesses, and, prescribe more targeted treatments. We have also started looking at a broader profile of the alterations in a cancer through molecular profiling, where hundreds of genes are examined for mistakes and abnormal copy numbers in an attempt to personalize care. Tailoring treatment to each person and their individual cancer characteristics at the cell level will become even more common in the coming years.
IMpassion130 also highlights the benefit of clinical trials not just for future patients, but also for those who are currently enrolled. I treated patients enrolled in this trial, and in fact, we still have patients who are receiving this therapy years after their diagnosis. This trial and this agent highlight the advances we make in cancer treatment every day through the power of clinical trials. Unfortunately, only about 2% to 5% of adults with cancer participate in clinical trials in the US and more than 50% say they are not even aware of the existence of trials.2,3 These studies show us that we need to continue to work toward making clinical trials a well-understood concept through patient education, dispelling misconceptions, and celebrating the big advances, such as the approval ofatezolizumab in this patient group.
Erika Hamilton, MD, is the Director of the Breast Cancer and Gynecologic Cancer Research Program at Sarah Cannon Research Institute in Nashville, Tennessee.
- Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial [published online November 27, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(19)30689-8
- Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 year of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383-1389
- Survey of Clinical Trial Awareness and Attitudes. http://subjectwell.com/wp-content/uploads/2016/03/Clinical-Trial-Awareness-Survey.pdf. Subject Well website. Accessed November 27, 2019.