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Immunotherapy and EGFR, ALK Inhibitors Deliver Precision Medicine in NSCLC

Gina Columbus @ginacolumbusonc
Published: Thursday, Dec 21, 2017

Now, we know that not only should you start with an EGFR TKI if a patient has an EGFR mutation present, but there are actually better EGFR TKIs out there in situations. Osimertinib brings the latest data set that shows an improved PFS over the traditional erlotinib or gefitinib drugs. There is still that small segment of uncommon mutations in which afatinib (Gilotrif) may be more appropriate for. Right now, osimertinib is rising to the top as far as the frontline choice.

What are your thoughts on PD-L1 as a prognostic biomarker?

There are [a lot] immunotherapies that are FDA approved out there. Several of them are in lung cancer, but most are in bladder cancer. Only one of them uses PD-L1 expression as a marker to determine treatment. There had been some criticisms about this marker. We are not crazy about expression or immunohistochemistry, especially as biomarkers, but we still use HER2 in that manner. I wish there was a better marker, but I am okay that we have PD-L1 as a biomarker, because it does tell us who should be treated in the first-line setting. No other drug has been able to demonstrate with PD-L1 expression or not that there is benefit in the frontline setting. Pembrolizumab does this with a PD-L1 score greater than 50%.

Now, again, you have a situation where you don’t have to use chemotherapy; that is a big deal for patients. Certainly, if you don’t have high expression, you can use chemotherapy—sometimes in combination with antiangiogenesis drugs, and then in the second-line setting you can use one of several approved drugs, including atezolizumab (Tecentriq) or nivolumab (Opdivo). 

For ALK-positive NSCLC, alectinib has now been approved in the first-line setting. What is the impact of this approval?

ALK NSCLC is another area that has transformed patient care. If you find an ALK translocation present, you can substitute a pill instead of chemotherapy. It is a smaller population of patients—4% to 6%. We have had several drugs, but we are now also seeing emerging, newer-generation drugs—alectinib in particular—that has shown a tremendously large PFS versus earlier traditional drugs like crizotinib (Xalkori).

Alectinib has really changed the standard of care in ALK-positive patients. Now, everyone is asking the question, "What do you do after alectinib?" There are some drugs out there being tested [such as] brigatinib (Alunbrig), and lorlatinib is coming. Perhaps you can resort back to the first-generation drugs, but alectinib is clearly one of the new super drugs like osimertinib. They both have characteristics where they have better PFS than traditional agents, they both penetrate the CNS reliably, and they both [have] less [severe] side effect profiles, which is, again, the whole package there. 

Precision medicine is a term thrown around frequently in lung cancer. How should community oncologists be thinking about and using it in their practice?

Precision medicine is a label that has evolved over time. When we practiced 20 years ago, precision wasn’t getting the exact histologic diagnosis. It was non–small disease versus small cell disease, or adenocarcinoma versus squamous versus non–small cell disease. We have evolved from superficial terminology, but we were still trying to be precise based on what the technology was.

Now, we have gone past just the histology. We have gone into, “What does the genomic signature say?” What are those markers telling us that is unique about these cancer cells? That is what has helped us stratify into whether you’re going to give somebody chemotherapy and you’re not sure what the benefit is—versus giving them a targeted agent where we have a very reliable and predictable benefit and more efficacy.

References

  1. Ramalingam S, Reungwetwattana T, Chewaskulyong B, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA. Presented at: 2017 ESMO Congress; Madrid, Spain; September 9-12, 2017. Abstract LBA2_PR.2.
  2. FDA Approves Genentech’s Alecensa (Alectinib) as First-Line Treatment for People with Specific Type of Lung Cancer. Genentech. Available at: http://bit.ly/2zmLda7. Accessed November 6, 2017.



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TitleExpiration DateCME Credits
Medical Crossfire®: Leveraging Liquid Biopsies in Tumor Characterization for NSCLC TherapyJan 31, 20181.5
Oncology Best Practice™: Choosing Therapies for Patients with EGFR-Mutant Lung Cancers: More Options... More Decisions... Better OutcomesFeb 28, 20182.0
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