Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses the available EGFR TKIs in the frontline setting for the treatment of patients with 

-positive non—small cell lung cancer (NSCLC).

Currently there are 5 FDA-approved TKIs indicated for frontline treatment of patients with 

-positive NSCLC; these include erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), dacomitinib (Vizimpro), and osimertinib (Tagrisso).

Most notably were the results of the phase III FLAURA study, which prompted the FDA approval of osimertinib in April 2018. In the trial, patients were randomized to receive either osimertinib, gefitinib, or erlotinib. Investigators reported a significant improvement in progression-free survival (PFS) in patients who received osimertinib; overall survival (OS) data are still maturing. Overall, the therapy was well tolerated with low incidences of rash. The study was practice-changing, says Clarke.

In 2018, the FDA also approved dacomitinib, which shows higher rates of grade 3/4 diarrhea and rash compared with gefitinib. However, an improvement in PFS as well as OS has been seen with dacomitinib. At this point, most [healthcare providers] feel that osimertinib remains the preferred frontline therapy based on tolerability and PFS benefit, concludes Clarke.

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Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses the available EGFR TKIs in the frontline setting for the treatment of patients with EGFR-positive non–small cell lung cancer (NSCLC).

Dr. Clarke on Available EGFR TKIs in Frontline Treatment of EGFR+ NSCLC

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses combination approaches beyond progression on osimertinib (Tagrisso) in 

-mutant non—small cell lung cancer (NSCLC).

Several studies have looked at anti-VEGF therapies in combination with anti-EGFR therapies and have shown a consistent improvement in progression-free survival (PFS), says Clarke. However, one study that came out of Japan in 2018 showed that there was no improvement in overall survival with the combination of bevacizumab (Avastin) and erlotinib (Tarceva) compared with erlotinib alone, calling into question the future role of these agents.

In terms of anticipated approaches, data regarding the combination of ramucirumab (Cyramza) and erlotinib are expected, says Clarke. According to a press release, treatment with the combination led to an improvement in PFS. Additionally, there have been studies looking at different therapies following progression on osimertinib. Exciting data from the phase Ib TATTON study showed response rates ranging from 30% to 50% with the combination of savolitinib and osimertinib and a median duration of response of 8 months. Overall, physicians are looking at the rationale for combinations following progression on osimertinib, concludes Clarke.

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses combination approaches beyond progression on osimertinib (Tagrisso) in EGFR-mutant non–small cell lung cancer (NSCLC).

Dr. Clarke on Combination Approaches Beyond Progression on Osimertinib in Lung Cancer

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, compares EGFR TKIs in 

Both osimertinib (Tagrisso) and dacomitinib (Vizimpro) are FDA approved for the frontline treatment of this patient population, but osimertinib has emerged as the preferred agent in this setting. Clarke says that osimertinib, a third-generation EGFR TKI, has a longer median progression-free survival and a more favorable toxicity profile than dacomitinib, a second-generation irreversible pan-HER TKI.

Osimertinib appears to spare normal tissue better than other EGFR inhibitors, while dacomitinib is a potent drug, Clarke adds. Dacomitinib demonstrated an improvement in overall survival (OS) compared with gefitinib (Iressa) in the phase III ARCHER 1050 study. Researchers are still waiting for OS data with osimertinib, says Clarke. In terms of toxicity, osimertinib has lower rates of grade 3/4 adverse events with less incidence of rash and diarrhea.

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, compares EGFR TKIs in EGFR-positive non–small cell lung cancer.

Dr. Clarke Compares TKIs in EGFR+ NSCLC

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses the evolution of biomarkers in directing treatment for patients with non—small cell lung cancer (NSCLC).

The use of biomarkers in NSCLC can help guide treatment. Biomarkers can be classified by genotyping and immune therapy. There are a couple of different ways to perform genotyping for lung cancer patients, either using tissue-based or plasma-based methods. Plasma-based methods, such as the use of liquid biopsies, can be particularly useful in sparing patients from the risks of tissue-based procedures.

On the immune-oncology side, PD-L1 measurement and expression remains the most well-validated and widely used biomarker in lung cancer, says Clarke. PD-L1 is a dynamic and heterogeneous biomarker, but it can be problematic because patients can have high expression and not respond to immune therapy and have low expression and respond well to immunotherapy.

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses the evolution of biomarkers in directing treatment for patients with non–small cell lung cancer (NSCLC).

Jeffrey M. Clarke, MD

Articles

Dr. Clarke on Available EGFR TKIs in Frontline Treatment of EGFR+ NSCLC

Dr. Clarke on Combination Approaches Beyond Progression on Osimertinib in Lung Cancer

Dr. Clarke Compares TKIs in EGFR+ NSCLC

Dr. Clarke on the State of Biomarkers in NSCLC