EGFR Testing for Metastatic Non-Small Cell Lung Cancer with Jonathan W. Riess, MD, MS: Case 1 - Episode 7
Jonathan Riess, MD, MS:In terms of safety and efficacy data for osimertinib, there has been a number of presentations and publications. I think the most pertinent is the New England Journal of Medicine publication in 2015 by Dr. Jänne and his colleagues that found for patients treated with osimertinib, the response rate was about 60% in patients who had T790M-positive EGFR-mutant lung cancer with a median progression-free survival of about 9.6 months. In patients who were EGFR T790M-negative, the response rate was only about 20%. And those that progressed right after an EGFR TKI, it was even lower than that. The median progression-free survival was about 2.8 months, so it’s a big differential. That data are essentially what have changed the standard of care for T790M-positive EGFR-mutant nonsmall cell lung cancer.
In terms of safety data, generally osimertinib is more EGFR wild-type sparing than erlotinib or afatinib and the other earlier generation EGFR TKI. But, it more potently inhibits T790M and then also inhibits the EGFR-activating mutation, such as exon 19 deletion and L858R. It has similar side effects to previous generation EGFR TKI inhibitors in terms of rash and diarrhea. In my experience, it’s been reported that it’s a bit attenuated because it’s more EGFR wild-type sparing, so patients generally tolerate it better than the previous EGFR inhibitor that they were on.
Other side effects to watch out for would be monitoring with a baseline echocardiogram based on the package insert. There wasn’t a comparator, but there was a low rate; less than 2% of congestive heart failure reported as well as EKG monitoring. There’s also a risk of pneumonitis as with in other EGFR TKIs. So, that’s something that’s rare, but does happen. That’s another thing to look out for in terms of side effects from osimertinib, but generally it’s been well tolerated in the patients that I’ve treated. You still need to watch out for those side effects. The safety and efficacy profile is very favorable for patients that have the EGFR T790M mutation.
Riess case 1:
A 44-year-old female with relapsed stage IV adenocarcinoma.