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Clinicians Slow to Adopt PD-1, PD-L1 Inhibitors in NSCLC


A significant subset of patients continues to receive chemotherapy monotherapy despite the availability of newer approaches, including programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors.

The approvals of programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors have led to a significant shift in first-line therapeutic choices in patients with non–small cell lung cancer (NSCLC), in the United States, although many patients are still treated with chemotherapy alone, according to a new report in Cancer Medicine.

The FDA ushered in a new era of NSCLC therapy in 2015 when it approved pembrolizumab (Keytruda) as monotherapy for tumors with high levels of PD-L1 expression. Since then, the indication has expanded and several other agents, including atezolizumab (Tecentriq) and nivolumab (Opdivo) have gained approvals in NSCLC, further widening the list of options for patients.

Yet, in this new report, the study authors note research looking into how the approvals have changed real-world therapeutic choices is sparse.

In their investigation, funded by BeiGene, the study team used the IBM MarketScan database to identify patients who began first-line treatment for NSCLC between May 2017 and October 2020. Their goal was to analyze first-line treatment choices and see if the availability of PD-1 and PD-L1 inhibitors led to any shifts in treatment practices in the United States.

The authors identified 5431 patients who began NSCLC therapy during the study period. Forty-seven percent were treated with chemotherapy alone, and most of the other patients were treated with a PD-1 or PD-L1 therapy. Twenty-five percent were given a PD-1 or PD-L1 inhibitor in combination with chemotherapy, 15% were treated with PD-1 or PD-L1 monotherapy, and 13% received targeted therapy.

Treatment patterns shifted significantly over time, the authors said.

“The proportion of patients who received PD(L)1i [inhibitor] monotherapy and targeted therapy remained relatively stable over these 4 years,” they wrote. “The percentage of patients receiving PD(L)1i with chemotherapy more than doubled during this same period.”

In 2017, 61% of patients received chemotherapy monotherapy, but that dropped to 38% by 2020. Meanwhile, just 13% of patients were given a PD-1 or PD-L1 inhibitor with chemotherapy in 2017. By 2020, 34% of patients received the combination therapy.

Although the trends suggest clinicians are increasingly turning toward newer therapies, the authors said there are significant barriers to wider adoption. Those include concerns about whether outcomes from a controlled clinical trial setting will match real-world outcomes and a lack of data regarding long-term adverse effects.

The analysis further showed that physicians were less likely to use PD-1 or PD-L1 inhibitors in patients older than age 65 and those with respiratory or kidney disease.

“Additionally, a higher proportion of males to females received PD(L)1i monotherapy use—a possible explanation may be that higher smoking rates in males are associated with higher tumor mutation burden and increased PD-L1 expression,” the investigators wrote.

They noted their database is limited to patients with commercial insurance, and so it may not fully reflect treatment patterns among older patients on Medicare. They also said the data set did not allow them to evaluate the reasons for the treatment decisions made for certain patients.

Still, the investigators said the data show that a significant proportion of patients are still not receiving the latest therapies. They said it is important to conduct further research to better understand why that is.

“As more immunotherapy agents and combinations are approved and used in clinical practice, practice patterns should continue to be evaluated to ensure NSCLC patients are receiving optimal treatment,” they concluded.


Veluswamy R, Hirsch FR, Taioli E, et al. Real-world longitudinal practice patterns in the use of PD-1 and PD-L1 inhibitors as first-line therapy in patients with non-small cell lung cancer in the United States. Cancer Med. Published online May 2, 2022. doi:10.1002/cam4.4785

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