publication date: Apr. 10, 2020

Clinical Roundup

Phase III TNBC ASCENT study to be stopped for compelling efficacy

The phase III confirmatory ASCENT study—designed to validate the promising safety and efficacy data of sacituzumab govitecan observed in a phase II study of heavily pretreated patients with metastatic triple negative breast cancer—will be halted due to compelling evidence of efficacy.

The primary endpoint for the study is progression-free survival, and secondary endpoints include overall survival and objective response rate, among others. This decision was based on the unanimous recommendation by the independent data safety monitoring committee during its recent routine review of the ASCENT study.

Immunomedics Inc. sponsors the trial.

“The remarkable results we observed across multiple endpoints in the ASCENT study warranted early discontinuation of the trial and are indicative of a potential major advance in the treatment of this devastating disease that affects younger women and African American women at higher rates,” Julie R. Gralow, Jill Bennett Endowed Professor of Breast Cancer, University of Washington School of Medicine and member of Fred Hutchinson Cancer Research Center, said in a statement.

A biologics license application resubmission seeking accelerated approval of sacituzumab govitecan for the treatment of patients with mTNBC who have received at least two prior therapies for metastatic disease is under FDA review, with a PDUFA target action date of June 2, 2020. The FDA previously granted Breakthrough Therapy Designation for sacituzumab govitecan in this disease setting.


Roswell Park reports extended survival among breast cancer survivors who exercise regularly

Following physical activity guidelines from the U.S. Department of Health and Human Services can improve clinical outcomes for patients with high-risk breast cancer, according to a study published in the Journal of the National Cancer Institute.

Researchers at Roswell Park Comprehensive Cancer Center conducted the study, which was led by Rikki Cannioto, assistant professor of oncology in the Department of Cancer Prevention and Control at the Buffalo cancer center.

Among people with high-risk breast cancer, those who engaged in moderate-to-vigorous levels of physical activity before and after their diagnosis had a statistically significant reduction in their chance of cancer recurrence or death. The work is the first report to show that physical activity measured at time points before, during and after chemotherapy is associated with outcome in those with high-risk breast cancer.

The HHS’ Physical Activity Guidelines for Americans recommend that adults engage in at least 2.5 to 5 hours of moderate-intensity physical activity or 1.25 to 2.5 hours of vigorous-intensity aerobic physical activity per week.

Cannioto et al. surveyed 1,340 people with high-risk breast cancer who were enrolled in the Diet, Exercise, Lifestyles and Cancer Prognosis (DELCaP) Study to determine whether meeting those minimum levels of activity at four time periods before diagnosis, during treatment and after treatment was associated with disease recurrence and/or mortality.

“When considering activity from before diagnosis and after treatment, we found that patients meeting the minimum Guidelines at both time points experienced significantly reduced hazards of disease recurrence and mortality—55% and 68%, respectively,” Cannioto said in a statement.

Importantly, patients who did not meet the physical activity guidelines before diagnosis, but who reported meeting the guidelines at their two-year follow-up experienced a significant survival advantage of 46% decreased chance of recurrence and 43% decreased chance of mortality.

When combining physical activity data from all four time points before, during and after treatment, they found striking inverse associations between mortality and physical activity at all activity levels, demonstrating that patients who consistently engaged in lower volumes of regular, weekly physical activity experienced similar survival advantages as patients who met or exceeded the guidelines.

“Taken collectively, these findings have important implications in the clinical oncology setting, because they suggest that a cancer diagnosis may serve as an impetus for increasing physical activity in some patients, and among these patients, beginning an exercise program after treatment resulted in a survival advantage,” Cannioto said.

“These observations coincide with previous findings from our group showing that lower levels of regular, weekly activity were associated with a significant survival advantage—which is encouraging given that patients and survivors can be overwhelmed by the current physical activity Guidelines,” Cannioto said.


Drug combination fights resistance to lung cancer treatment

A drug combination discovered by the UT Southwestern Simmons Cancer Center may extend the effectiveness of a lung cancer treatment and make it available to many more patients.

The findings, published in Nature Cancer, focused on epidermal growth factor receptor, EGFR, a protein that has a prominent role in the growth and survival of cancer cells, and resistance that builds up against inhibitors used to battle it. The researchers found that adding an interferon blocker, normally used to treat lupus, effectively wiped out this resistance in mice.

“This could be very important because it could expand the reach of the drug from about 15% to the majority of patients with lung cancer. That’s millions of people worldwide,” Amyn Habib, associate professor of Neurology and Neurotherapeutics at UT Southwestern Medical Center, a member of the Harold C. Simmons Comprehensive Cancer Center, and a staff physician at the Dallas Veterans Affairs Medical Center, said in a statement.

About 15% of lung cancer patients have a mutation in EGFR that makes it more active.

Habib’s lab discovered that the signaling pathways release interferons that resist the EGFR inhibitor. It was an unexpected finding because oncologists normally see interferons as allies in fighting cancer.

Their broad search included drugs outside of cancer treatment and found an interferon blocker used in lupus patients called anifrolumab. The researchers used anifrolumab to block interferons in mice, crippling the signaling pathway and wiping out the resistance to the EGFR blocker.

They also found that patients who did not have mutated EGFR also increased their interferon levels in response to EGFR inhibitors. This has kept those patients from responding to the EGFR inhibitor drugs. If the lupus drug could block the interferons, it would also open those patients up to the benefits of the EGFR blocking drugs.

Habib’s lab made the discovery by focusing on about 3,000 genes in the lung cancer cell and charting that were turned on or off. The data clearly led the researchers to increased activity with interferons.

This was previously unknown to medical science, and it is significant because EGFR signaling plays a role in other cancers including breast cancer and glioblastoma. Habib says his next step is to pursue clinical trials in lung cancer patients.

Other authors of the study from UT Southwestern are Ke Gong, Gao Guo, Nishah Panchani, Matthew Bender, David E. Gerber, John D. Minna, Farjana Fattah, Boning Gao, Michael Peyton, Kemp Kernstine, Cheng-Ming Chiang, Adwait Amod Sathe, Chao Xing, and Esra A. Akbay. Authors from other institutions are Kathryn H. Dao of Baylor Research Institute in Dallas, Dawen Zhao of Wake Forest School of Medicine in Winston-Salem, North Carolina, and Sandeep Burma and Bipasha Mukherjee, both at the University of Texas Health Science Center at San Antonio.

Copyright (c) 2020 The Cancer Letter Inc.