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Effective lung cancer treatment requires precision medicine
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NEW YORK — Oncologists should know the biomarker status of EGFR, ALK, ROS1, BRAF or PD-L1 before the use of chemotherapy to treat lung cancer patients, according to a presenter at Chemotherapy Foundation Symposium.
This is similar to the need to identify HER-2 status among patients with breast cancer prior to beginning treatment.
“I think we are in a precision medicine field, and lung cancer is a model of this and patients should not be treated until [an oncologist] has this information,” Edward S. Kim, MD, chair of solid tumor oncology and investigational therapeutics at Levine Cancer Institute, told HemOnc Today. “It is part of the diagnostic workup.”
Kim, a HemOnc Today Editorial Board member, presented a session about how to best choose an EGFR tyrosine kinase inhibitor for the treatment of patients with lung cancer based on available research.
“It’s really been an exciting last couple of years for EGFR,” Kim said. “This is an area where it has been put off to the side a little bit because of all the excitement around ALK, PD-L1 and ROS-1 and all these other mutations. To actually see that there have been some therapeutic changes over the last couple of years is really nice, because this is what oncologists like, to be able to apply results to the clinic.”
The era of first-line treatment with an EGFR TKI started with erlotinib (Tarceva; Genentech, Astellas) and gefitinib (Iressa, AstraZeneca), and then a newer generation drug afatinib (Gilotrif, Boehringer Ingelheim), which also was indicated in the first-line setting and more specifically showed additional activity among patients who harbored a specific exon 19 deletion EGFR mutation, according to Kim.
“Previously, we had just considered all the EGFR mutations the same, but that's no longer true,” he said. “We have to look at the individual mutations and make sure [we know] what we have.”
Since then, osimertinib (Tagrisso, AstraZeneca) has come on the scene targeting T790M — a resistance mutation that occurs after treatment with an EGFR TKI, which occurs 50% to 60% of the time.
The strategy now, as Kim said, is to find an EGFR mutation and give the patient a TKI that best treats the disease — Kim’s institution uses afatinib. Typically, a patient will receive treatment for a year or two, and then the drug will begin to lose its effect, he said. Once the tumor starts to grow again, a patient undergoes another biopsy and, in approximately 50% to 60% of cases, a T790M mutation is identified and patients receive osimertinib.
“That’s 2-plus years of treatment, with pills; we’re not talking about IV chemotherapy, we’re not talking about hair loss, we’re not talking about reduced blood counts, and that is so amazing to do in lung cancer,” Kim said. “It is a similar reminder of metastatic breast cancer, where the physician can just keep doing the hormone therapies and cycle them until things get worse.”
Kim noted that erlotinib is not used to treat any wild-type indications, nor as a second-line, third-line or maintenance treatment.
“That’s the first change: We are being more marker specific,” he said.
Additionally, the randomized phase 3 FLAURA trial demonstrated that giving osimertinib — compared with erlotinib or gefitinib — upfront among patients with a sensitizing mutation demonstrated a PFS improvement of 9 or more months.
“That is now changing the standard of care, and the standard of care now will be first-line in these specific mutations,” Kim said.
However, Kim acknowledged that oncologists will likely question what to use as a second-line agent after osimertinib in the upfront setting.
He advises that markers are being investigated and developed, including C797S which has an early marker that seems to confer resistance to osimertinib, he said.
Although there is not yet much known about the incidence, as more patients are treated with osimertinib, that will be easier to define.
“Anecdotal evidence shows that first-generation TKIs actually can target this mutation, so we might actually be flipping the script the other way and patients may still be on pills for several years, it just might be in the reverse order, depending on the incidence of this,” he said. “I'm confident with the way immunotherapy is entering the market, the way drug development is occurring with combinations and the safety profiles of some chemotherapies, and combinations, that we’re going to have solutions for this situation. I really think it is important to use the best drug first because we know that we don't necessarily have every opportunity in the world to treat patients, so when we do have them in front of us and they’re feeling well, we should treat them with the most effective agent.” – by Ryan McDonald
Reference:
Kim ES. Choosing a First-Line EGFR TKI: What Do the Data Tell Us in 2017? Presented at: Chemotherapy Foundation Symposium; Nov. 8-10, 2017; New York.
Disclosure: Kim reports consultant roles with AstraZeneca, Boehringer Ingelheim, Celgene and Eli Lilly.