Helen J. Ross, MD, medical oncologist, Banner MD Anderson Cancer Center, discusses toxicity concerns with combinations therapies in 

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

In cases of resistance to first-, second-, or third-generation EGFR inhibitors, combination therapies have been evaluated, says Ross. For example, if a patient develops resistance to osimertinib (Tagrisso), adding agents such as gefitinib (Iressa) or erlotinib (Tarceva) could be beneficial, Ross explains. However, on-target toxicities, such as inflammation, irritation, gastrointestinal toxicities, and skin toxicities, have limited the utility of this treatment approach, says Ross.

Similarly, evaluation of combination TKIs and immunotherapy was halted because of severe immune-related toxicities, including cardiac and pulmonary adverse effects (AEs), in this patient population, Ross explains. As such, developing a better understanding of the mechanisms of these toxicities, as well as identifying whether a specific patient population may have a lower risk of developing severe AEs, could allow these combination approaches to enter the treatment paradigm, concludes Ross. 

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Helen J. Ross, MD, discusses toxicity concerns with combinations therapies in EGFR-mutant non–small cell lung cancer. 



Dr. Ross on Toxicity Concerns With Combination Therapies in EGFR+ NSCLC 

Helen J. Ross, MD, medical oncologist, Banner MD Anderson Cancer Center, discusses the utility of first- and second-generation EGFR inhibitors in 

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

Since the 2018 FDA approval of osimertinib (Tagrisso) for the frontline treatment of patients with 

-mutant metastatic NSCLC, the use of first- and second-generation EGFR inhibitors has declined, says Ross. However, certain circumstances may warrant using a first- or second-generation agent vs osimertinib. For example, some patients with 

-mutant NSCLC who develop resistance to osimertinib may still be sensitive to a first- or second-generation inhibitor, says Ross. Research efforts are ongoing to understand which patients may require this treatment approach, Ross adds. 

In general, patients in the United States will receive osimertinib in the frontline setting, explains Ross. Moreover, based on the survival advantage noted with osimertinib vs gefitinib (Iressa) or erlotinib (Tarceva) in the phase 3 FLAURA trial (NCT02296125), it is likely that osimertinib is the optimal treatment approach for this patient population, Ross says. Additionally, utilizing osimertinib as a first-line therapy is warranted because approximately 20% to 30% of patients with NSCLC will not receive second-line therapy. Ultimately, it is important to utilize the most effective agent up front, Ross explains.

Notably, patients who were receiving a first- or second-generation EGFR inhibitor prior to the approval of osimertinib should remain on therapy if they are tolerating it and have disease control, Ross concludes.

Helen J. Ross, MD, discusses the utility of first- and second-generation EGFR inhibitors in EGFR-mutant non–small cell lung cancer. 



Helen J. Ross, MD

Articles

Dr. Ross on Toxicity Concerns With Combination Therapies in EGFR+ NSCLC

Dr. Ross on the Utility of First- and Second-Generation EGFR Inhibitors in EGFR-Mutant NSCLC