Incorporating Real-World Evidence into Clinical Decisions in NSCLC - Episode 5

Referring to Real-World Evidence When Managing EGFR-Mutant NSCLC

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Information provided by real-world data that is noted to be the most valuable to thoracic oncologists and others who manage patients with EGFR-mutant non–small cell lung cancer.

Lyudmila Bazhenova, MD: For the next polling question we have: For which of the following types of information do you see the most value in real-world evidence? Go ahead and answer. Your options are effectiveness in real-world clinical practice, patient subgroups not routinely included in clinical trials, and real-world safety and management of adverse events.

Dr Albrecht, can you comment on the results of this poll?

Federico Albrecht, MD:Can you tell me the percentages?

Lyudmila Bazhenova, MD: Eighty percent of the people felt that patient subgroups not routinely included in clinical trials are the most likely to be used. No. 2 was effectiveness, and 0% answered real-world safety.

Federico Albrecht, MD:Great. I agree with the group because the randomized controlled trials many times exclude a different subgroup of patients than we encounter in the clinics, and we want to know if that specific medication, in this case a TKI [tyrosine kinase inhibitor], will help patients with certain EGFR mutations. For example, there was a sample of a paper that showed a randomized controlled trial. For randomized controlled trials, many papers included only patients with exon 19 and exon 21 and excluded many mutations that were uncommon but seen in many patients with lung cancer. Whether a TKI was effective in patients was not answered by the randomized clinical trials. Many retrospective observational studies showed that afatinib was active and effective in patients with uncommon mutations. This is an important observational real-world study—actually a combination of real-world evidence—that led 1 of our regulatory agencies, the FDA, to approve afatinib for uncommon mutations. This is a clear example of how a regulatory agency can accept and interpret data and real-world evidence and formulate an indication. This is very important.

The other important thing is that many physicians want to know what to do with patients with brain metastases. Brain metastases were often not included in those randomized clinical trials. This real-world evidence trial showed, and there were samples in this paper, that the outcome of patients who received TKI was inferior for patients with brain metastases. However, the TKI, in this case afatinib, showed an advantage for first-generation TKIs. In this way, when we encounter these type of patients, we can feel reassured. For patient subgroups not routinely included in those clinical trials, with this type of information we know we can treat those patients in our clinic.

This is real-world evidence that you can use a TKI and know that that patient may benefit from it. That’s the benefit of real-world studies. There are some limitations—Dr Bazhenova touched on them—but that’s complementary information. That’s my take on this polling question.

Lyudmila Bazhenova, MD: I can’t agree with you more. In addition to the groups you mentioned, we have patients with leptomeningeal carcinomatosis. If we’re talking about the EGFR population, those patients have a high risk of developing leptomeningeal disease, especially the longer they survive on EGFR TKIs. Unfortunately, those patients are routinely excluded from clinical trials. The only evidence we have for those patients is 1 clinical trial, called BLOOM, which looks at osimertinib in leptomeningeal disease. The rest of the data we have are from real-world evidence—prospective, retrospective, and case series. It’s very important because we have to treat the patients and give them some idea of how effective the treatment is. At this point the only information we can give our patients is from real-world evidence, so I agree with you that it’s absolutely complementary.

Transcript edited for clarity.