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Originally published September 9, 2026
Last updated September 10, 2026
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Clinical trials are the gold standard for choosing evidence-based treatments. But increasingly, real-world analyses are going to be required to help validate results in diverse populations that are more representative of the United States today.
“Clinical trials occur in a very select population of patients,” says Jorge J. Nieva, MD, a medical oncologist with the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC. “Most people don’t qualify for clinical trials because they’ve got some other comorbidity. Or they fall outside of the treatment window. Or they simply don’t want to participate in a clinical trial for whatever reason. This is common with Americans who don’t like the randomization assignments.”
In situations like these, analyses from large datasets can be used to validate which treatments are actually effective in the real world.
That was the thinking behind a recent study led by Keck Medicine researchers who used insurance claims data to study the effectiveness of five tyrosine kinase inhibitors (TKIs) to better understand differences in how the drugs affect patient outcomes in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer.
“Because we’ve shifted much of our clinical trial infrastructure overseas, the patients are a little less representative of the United States,” says Nieva, the study’s senior author. “People want to be sure that the findings from clinical trials really do apply to an American population. Our real-world populations are often much older than people who enroll in clinical trials. They’re often a little bit frailer. And so real-world data helps us ensure that what was applicable to a young, healthy overseas population is also very applicable to a U.S. population.”
The growing number of FDA-approved TKIs for first-line treatment of ALK+ lung cancer has made treatment selection increasingly complex. Although current National Comprehensive Cancer Network (NCCN) guidelines endorse four TKIs as equivalent first-line options for advanced ALK+ disease, clinical trial findings may not completely represent outcomes in broader, real-world patient populations.
In their analysis, researchers compared insurance data from 940 patients who used crizotinib, alectinib, lorlatinib, brigatinib and ceritinib (which is not a preferred NCCN treatment) between 2016 and 2024. The study was the first to investigate the real-world use of the newer ALK inhibitors lorlatinib and brigatinib outside clinical trials. Its findings, recently published in Lung Cancer, offer important guidance to patients and physicians when weighing treatment options.
“We found that our real-world results closely mirrored those reported in clinical trials,” Nieva says. “For example, in the ALEX trial comparing alectinib and crizotinib — the two most commonly used ALK inhibitors in our dataset — alectinib demonstrated superior progression-free survival. We observed a similar pattern in our real-world analysis, with patients remaining on alectinib treatment for longer periods. The strong concordance between our findings and the clinical trial data increases confidence in both the validity of our study and the evidence supporting the comparative effectiveness of these therapies.”
One of the biggest challenges of this study was the availability of follow-up data.
“Patients with ALK+ lung cancer thankfully live a long time. That means, however, that you can’t look at outcomes just one or two years into drug treatment; you’ve got to look at outcomes five and 10 years into drug treatment to really see differences between groups,” Nieva says.
The researchers used either time to treatment discontinuation or death as a surrogate for progression-free survival. “In retrospective data sets, you can’t do CT scans like you would in clinical trials to measure progression-free survival, so instead, we measure how long the patient remains on a drug and we consider that a surrogate for how long it was until the tumor became resistant and started to grow through the drug,” Nieva says.
The data came from Optum’s Clinformatics Data Mart database, “but we didn’t have indefinite access to the database,” Nieva explains. “So, we had to make sure that the publication review happened while we still had access. And actually, we had to push the publisher to get the reviews done and finalized quickly, because there came a time when if we were asked to make any revisions or edits or ask any additional questions of the data set, it was no longer going to be available to us.”
The biggest takeaways for practicing oncologists? “The study makes it very clear that crizotinib probably shouldn’t be used as the initial agent anymore,” Nieva says. “That’s something that’s already been known from clinical trial literature. But this study reinforces that.”
The study can also help with cost-savings decision making, he adds. “For example, there may have been temptation by some to say, ‘Alectinib is not generic, but crizotinib now is, and the prices of crizotinib have gone way down. Is it safe to substitute a generic?’ And I think the answer that we have here is no. It’s not a good idea to use something like generic crizotinib instead of alectinib,” Nieva says.
For rare tumors like those in ALK+ lung cancer, oncologists have a lot of options and may also wonder if their course of treatment is the most contemporary choice.
“At Keck Medicine, we’re happy to help clinicians who are taking care of patients with rare diseases by providing second opinions to reinforce their treatment selection, perhaps modify it or talk about clinical trials that the patients may want to participate in,” Nieva says. “I’m always happy to be a resource for clinicians who are dealing with rare subtypes of diseases to help make sure that they have confidence their patient is getting the most contemporary option available.”
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