Study Explores Immunotherapy vs. Chemoimmunotherapy Decisions For Advanced Non-Small Lung Cancer

In treating advanced non-small cell lung cancer (aNSCLC), the choice between immunotherapy alone and chemoimmunotherapy (a combination of chemotherapy with the newer immunotherapy agents) depends on several factors. Clinical guidelines typically do not favor one treatment over the other. Both options have shown similar outcomes in patients with a high proportion of lung cancer cells expressing programmed cell death ligand 1 (PD-L1), a biomarker often linked to cancer aggressiveness. Real-world treatment decisions are far from straightforward.

Results of a study published last month in JAMA Network Open explore the factors that may influence clinicians' choices, revealing that age, performance status, healthcare setting and socioeconomic factors all play a role in determining whether patients receive immunotherapy alone or in combination with chemotherapy.

Some of the FDA-approved immunotherapy agents used to treat NSCLC are Opdivo (nivolumab), Keytruda (pembrolizumab) and Imfinzi (durvalumab).

Researchers from the University of Pennsylvania in Philadelphia and Emory University in Atlanta analyzed first-line treatment data from more than nearly 5,500 patients with aNSCLC. About half (2,690, or 49.4%) received just immunotherapy, and the majority (3,119, or 57.3%) were PD-L1 high. Tumor proportion scores determine whether a patient’s disease is categorized as a high or low PD-L1. As the name suggests, the scores are the proportion of tumor cells that express PD-L1. When 50% or more of the cells express PD-L1, those cancers are deemed high PD-L1.

In this study, factors favoring the use of immunotherapy monotherapy included older age (over 75), poorer performance status (ECOG score of 2 or higher), being treated at academic medical centers, female sex, the presence of brain metastases, and concurrent use of anti-infectives. In contrast, factors favoring chemoimmunotherapy included higher socioeconomic status, being uninsured, a more recent diagnosis and prior glucocorticoid/steroid use.

“Chemoimmunotherapy use increased, relative to immunomonotherapy, from 2018 to 2024,” lead author Vinayak S. Ahluwalia, a medical student at the University of Pennsylvania, said in an interview with Managed Healthcare Executive.

“In the PDL1-high group, immunotherapy alone was more likely to be prescribed at academic medical centers, whereas patients with the highest socioeconomic status received chemoimmunotherapy more often than those with the lowest socioeconomic status,” Ahluwalia said. “These findings suggest differences in the treatment regimens based on practice setting or socioeconomic status.”

In the research letter, Ahluwalia and his co-author, Ravi B. Parikh, M.D., M.P.P., of Emory University, said the difference in treatment according to socioeconomic status could be explained by “well-resourced patients being able to leverage a support system while undergoing chemotherapy.”

They said the finding that uninsured patients were also more likely to receive chemoimmunotherapy "should be investigated further."

Although both immunotherapy and chemoimmunotherapy are effective for those with high PD-L1 expression, the study's results suggest that clinicians increasingly opt for chemoimmunotherapy as treatment time progresses, despite similar outcomes reported for both options in clinical trials. The choice seems to be further shaped by practical factors, such as access to healthcare.

Another notable finding was that steroid use prior to treatment decreased the likelihood of receiving immunotherapy alone. This aligns with research suggesting that these steroids may reduce the efficacy of immunotherapy, leading some clinicians to opt for chemotherapy.

This study does have some limitations. For one, there were more White patients in the group than those from minoritized racial and ethnic backgrounds, which could make it harder to fully understand racial disparities. Also, although the authors considered factors like performance status and the presence of bone and brain metastases, they were unable to account for signs of rapidly progressing disease, which often lead to the addition of chemotherapy for patients with high PD-L1.