News Release
ronac mamtani
Ronac Mamtani, MD

PHILADELPHIA—Real-world evidence is suggesting, for the first time, the most beneficial treatment courses that could help extend the lives of patients with metastatic non-small cell lung cancer, according to research from the Abramson Cancer Center at the University of Pennsylvania.

In a new study published online today in JAMA Oncology, researchers show that patients harboring a KRAS gene mutation with high levels of PDL-1 lived longer when treated with immunotherapy alone, compared to patients without this mutation. This survival difference by KRAS status was not seen, however, in patients treated with both chemotherapy and immunotherapy, suggesting combination therapy for patients without the mutation may be preferred.

The new findings, based off an analysis of the Flatiron Health database that includes aggregated, de-identified data from the electronic health records of more than 65,000 patients with advanced non-small cell lung cancer, provide much-needed guidance to treat a disease that has a five-year survival of just 35 percent.

“This is a prime example of how real-world data can complement clinical trial data to help inform decision making between patients and their oncologists,” said senior author Ronac Mamtani, MD, an assistant professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania.

lova sun
Lova Sun, MD

Oncologists have several options to treat patients with metastatic non-small cell lung cancer and high levels of the immune biomarker known as PD-L1, including checkpoint inhibitors such as pembrolizumab or atezolizumab, which block different proteins, like PD-1 and PDL-1, that keep T cells from killing cancer cells.  The therapy has changed the treatment landscape for many cancers, including lung, and is often paired with chemotherapies; however, which treatments or combination of treatments are best suited for patients with the KRAS mutation has been unclear.

“Many of the treatment decisions for these patients are imperfect and non-data driven, with no biomarkers to help guide them,” said first author Lova Sun, MD, a fellow in the division of Hematology-Oncology in the Perelman School of Medicine. “This study shows us an important piece of the molecular data, which is something the field hasn’t had.”

In the exploratory analysis of four years of clinical data that included more than 1,100 patients, the researchers found that about half of the patients with PDL-1 levels higher than 50 percent tested positive for a KRAS mutation.

Patients with KRAS mutation and treated with a checkpoint inhibitor alone had superior survival compared to patients without the mutation: 21.1 vs 13.6 months. Among patients treated with chemo and immunotherapy, however, there was no significant survival difference between patients with or without the mutation. Also, patients without the mutation treated with just immunotherapy had worse survival than those treated with chemo and immunotherapy (13.6 vs 19.3 months), although the difference was not statistically significant.

These findings are applicable to a large subset of lung cancer patients, the researchers said.

charu aggarwal
Charu Aggarwal, MD, MPH

“A third of patients with non-small cell lung cancer have high PD-L1, and of those patients, many have a mutation in KRAS,” said co-senior author Charu Aggarwal, MD, MPH, the Leslye M. Heisler Associate Professor for Lung Cancer Excellence in Penn’s Perelman School of Medicine. “There will be clinical implications for a large portion of patients with advanced lung cancer, as we learn more about this mutation and how other mutations may play a role in response.”

Penn co-authors on the study Miles Tan, Roger B Cohen, and Corey J. Langer.

The work was supported in part by the National Institutes of Health Cancer Clinical Epidemiology Training Grant (T32-CA-09679).

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $8.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $496 million awarded in the 2020 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.

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