A cancer diagnosis is usually unexpected, but especially so for a healthy 44-year old like Sara Vernon Sterman. After being diagnosed with non-small cell lung cancer, Sarah found out she was eligible for newer targeted drugs that could help rid her body of this disease.

Under the care of Dr. Charu Aggarwal, MD, MPH, Sara has tried three different drugs, including one that demanded a dietary schedule that she found very constraining. She now takes an alectinib (Alecensain®) pill daily with minimal to no side effects.

Dr. Aggarwal is optimistic about these new treatment methods and amazed by how much the science has developed since she began practicing medicine.

"I started my fellowship in 2008. At that time, we didn't have many options for lung cancer. It's so exciting to be able to look back and see, just in 10 years, we have 12 oral drugs available and six immunotherapy agents that have a role in lung cancer," reflects Dr. Aggarwal.

Dr. Aggarwal studies immunotherapy treatment for lung and head and neck cancers. Yet, like many cancer researchers at Penn, the scope of her work is wider because of her relationships with other doctors and scientists on campus — relationships fostered by the Abramson Cancer Center's Thoracic Oncology Translational Center of Excellence (TCE).

It typically takes at least five years for a biological breakthrough to evolve into a drug that may benefit people. The TCEs aim to accelerate the pace. In lung cancer, this means a focus on early detection and treatment, and most promisingly, treatment with immunotherapy. Most advanced non-small cell lung cancer patients at Penn now receive some form of immunotherapy as a first- or second-line treatment.

"Overall as a lung program, we are really changing the treatment paradigm for this disease," says Dr. Aggarwal. She points to a 2016 study that established a combination immunotherapy/chemotherapy as a first-line treatment for advanced non-small cell lung cancer. The study was led by Corey J. Langer, MD, Professor, who co-directs the TCE with Steven M. Albelda, MD, William Maul Measey Professor.

TCE members work together to come up with ideas and prioritize ones that have the most potential. "If you look across the landscape of immunotherapy, there are thousands of trials. The way to set it apart is to have the trials be based in the science, how these cancers work, and how we can target them best," says Joshua M. Bauml, MD, Assistant Professor, who also studies immunotherapies.

Strong relationships with philanthropy and industry help make this possible. "These relationships give us the opportunity to take our ideas to industry to do interesting science when other organizations or the government may not have the funding," adds Dr. Aggarwal.

Priority Areas of Research

Tests to Detect and Monitor Lung Cancer

Many people at risk for lung cancer do not get screened. Those who do run a risk of receiving false positive results. Science sees a future in blood tests, which are less costly and invasive than scans and tissue biopsies, and potentially more accurate.

Pulmonologist Anil D. Vachani, MD, MS, Associate Professor, focuses on finding better ways to screen people at high risk of developing lung cancer. One study, still in the early stages, relies on circulating DNA technology, and the expertise of Erica L. Carpenter, MBA, PhD, who directs the Circulating Tumor Material Center. "This is a population at risk. If we can provide them with more sensitive noninvasive monitoring in addition to the low-dose CT scans they already get as standard of care, this would be wonderful. It would give clinicians another tool to help these patients," says Dr. Carpenter.

Another line of research looks at blood tests to monitor or predict how lung cancer patients respond to treatment. Drs. Aggarwal and Albelda recently found that circulating tumor cells may help predict response to treatment in people with small cell lung cancer.

In advanced non-small cell lung cancer (NSCLC), liquid biopsy using circulating tumor DNA can detect genetic changes in a patient's tumor. This information helps doctors deliver personalized care without the need for an invasive biopsy. Dr. Aggarwal continues to collaborate with Dr. Carpenter to develop liquid biopsy in NSCLC, looking for response patterns in people treated with targeted therapy, immunotherapy, and chemotherapy.

Better Treatments, Better Outcomes

The Power of Combination Therapies

Immunotherapy has been a game-changer, but even the most effective drugs don't work for everyone. Penn studies explore new or better treatment options. They involve new forms of immunotherapy, combining therapies, or administering drugs in a different way or at a different phase in the treatment process.

As an example, Dr. Albelda and Sunil Singhal, MD, William Maul Measey Associate Professor, are trying to rev up immune response before lung cancer surgery. They use a viral vector to locally activate the immune response before removing the tumors surgically. It is hoped this strong immune response will prevent tumor recurrence. This line of research picks up on earlier gene therapy work in mesothelioma and lung cancer done at Penn by Drs. Albelda and Aggarwal. Dr. Singhal became interested in research as a fellow in Dr. Albelda's lab.

Dr. Bauml recently completed a study of immunotherapy after locally ablative treatment for patients with limited metastases, what physicians call "oligometastatic" disease. Preliminary findings have been very promising, and accrual to the trial was excellent. He is currently in discussions with multiple partners to determine the next step for this patient population.