Mitigating the Risk of New Cancer Therapies

Advances in lung cancer treatment have changed survival in ways that were unimaginable even a decade ago. Targeted drugs, immunotherapies, and emerging antibody—drug conjugates are helping many patients live longer—and live well. But these gains may come with risks, including one called drug-induced pneumonitis, an inflammatory reaction in the lungs that ranges from mild to life-threatening.

Yale School of Medicine’s Jennifer Possick, MD, and Kathleen McAvoy, MD, see this complication often. For them, the biggest challenge is that pneumonitis may not appear to be a dramatic medical event, and its symptoms resemble those of other respiratory illnesses. Their recent review, published in Seminars in Respiratory and Critical Care Medicine, aims to help clinicians better recognize these subtle signs before they escalate.

The risk of pneumonitis has grown as cancer therapies have evolved. Many drugs now used in lung cancer and other malignancies, including epidermal growth factor receptor (EGFR) inhibitors, anaplastic lymphoma kinase (ALK) inhibitors, immune checkpoint inhibitors, and several antibody–drug conjugates, can trigger lung inflammation. Patients with underlying lung disease or prior radiation are at higher risk, but even people without those factors can develop reactions.

Possick, associate professor of medicine in the Section of Pulmonary, Critical Care and Sleep Medicine (Yale-PCCSM) and medical director of the Winchester Center for Lung Disease, emphasizes that this uncertainty should not prevent patients from receiving therapies that can dramatically extend their lives. “Some people with serious underlying lung disease can receive treatment safely and benefit tremendously,” she says. “The challenge is that we don’t yet have a reliable way to predict who will do well and who might have a dangerous reaction.”

Because pneumonitis can be mistaken for more common conditions like COPD or respiratory infections, identifying the condition requires deliberate teamwork. Radiologists, oncologists, pulmonologists, and pharmacists all play a role in piecing together the clinical picture.

“We’re not on one side and the oncologist is on the other with the patient stuck in the middle,” Possick says. “We’re holding hands around the patient to figure out the safest way forward.”

Researchers are working to build better prediction tools. Biomarkers, radiomic imaging features, and artificial intelligence models show early promise, but McAvoy notes that the science is still developing. “It’s very grassroots right now,” she explains. “There is no single test that tells us who is at risk.”

In the meantime, the most powerful tool may be awareness among clinicians and patients. Possick encourages people to speak up early when subtle changes arise. “If someone tells us their cough seems different than usual, or they cannot walk as far as last week, those clues can matter more than anything else,” she says. That emphasis on recognizing small shifts is a central message in their published review, which they hope will benefit clinicians and patients alike.

“The review draws attention and provides comprehensive information to a phenomenon that is rising in importance but is still not fully understood and definitely requires much more research,” says Naftali Kaminski, MD, Boehringer Ingelheim Pharmaceuticals, Inc. Professor of Medicine and section chief of Yale-PCCSM. “At Yale, the close collaboration of the pulmonary and lung cancer teams puts us in an ideal position to make a difference in the understanding and management of lung cancer treatment-induced pneumonitis.”

Both Possick and McAvoy want patients to know that involving a pulmonologist in their cancer care is not a setback.

“Having a pulmonologist involved does not mean treatment is over,” Possick says. “It means we’re working to keep people feeling as well as possible for as long and safely as possible.”