The following article, written by Laura R. Bobolts, Senior Vice President of Pharmacy at Oncology Analytics, is the first of a four-part series on key trends and findings from the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, held in Chicago May 29-31, 2020.
Breast cancer is the most common cancer among women in the United States. A diagnosis of metastatic breast cancer can be devastating, especially if the cancer is an aggressive subtype called triple-negative disease.
Metastatic (or stage IV) breast cancer is cancer that starts in the breast and spreads to distant organs, most frequently the liver, brain, bones, and lungs. Although the cancer is not curable at this point, treatments can slow tumor growth, relieve symptoms, improve quality of life, and hopefully prolong life.
Roughly 10-15% of breast cancers are triple-negative—a subtype that tests negative for estrogen receptors, progesterone receptors, and HER2 protein expression, which leaves limited targeted treatment options, as the cancer will not respond to hormonal therapy or drugs that target HER2 receptors. Triple-negative disease is the most aggressive and one of the most difficult subtypes of breast cancer to treat, with a median overall survival of 13.3 months in the metastatic setting.
Earlier this year, Shannen Doherty, the actress of popular hit shows like “90210” and “Charmed,” revealed her breast cancer has returned and is now metastatic. Though Doherty did not share all the details of her recurrent disease, metastatic treatment options can vary significantly depending on subtype and biomarkers specific to an individual woman’s cancer. Shannen Doherty does not want to let cancer define her. “I think the thing I want to do the most right now is I want to make an impact,” she said. “I want to be remembered for something bigger than just me.” Doherty is now bringing awareness to a cancer that annually takes over 42,000 lives.
Recent advances have found targeted immunotherapy effective in treating certain triple-negative breast cancers. The immune checkpoint inhibitor drug, atezolizumab, was the first targeted agent to be approved for metastatic triple-negative breast cancer in combination with chemotherapy. Studies showed that atezolizumab is effective in the initial treatment of tumors positive for a protein called PD-L1.
Checkpoint proteins in the body, such as PD-L1 seen on tumor cells and PD-1 on T cells of the immune system, help keep immune responses in check. When PD-L1 binds to PD-1, the cancer hits the “off switch” on the immune system, allowing the cancer to hide and evade destruction. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor such as atezolizumab or a similar agent called pembrolizumab, allows the body’s own immune cells to see the cancer as foreign and kill it.
At ASCO 2020, researchers presented a promising study evaluating the immune checkpoint inhibitor, pembrolizumab, plus chemotherapy in patients with advanced or metastatic triple-negative breast cancer.
KEYNOTE-355 was a phase 3 study that randomized patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer to pembrolizumab plus chemotherapy or placebo plus chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). The addition of pembrolizumab to chemotherapy significantly reduced the risk of disease progression or death by 35% in tumors that expressed PD-L1. Patients who received pembrolizumab plus chemotherapy had progression-free survival (time from start of treatment to disease progression or death) of 9.7 months compared to 5.6 months with chemotherapy alone.
Given these results, pembrolizumab will soon join atezolizumab as a likely effective addition to chemotherapy in the first-line treatment of patients with PD-L1 positive, metastatic triple-negative breast cancer. We eagerly await longer-term data to determine whether the addition of pembrolizumab, as studied here, prolongs the overall survival of cancer patients.
Despite these exciting advances, new treatment options are urgently needed in this difficult to treat subtype of metastatic breast cancer.