Additional EGFR-TKI Therapy Research in NSCLC

Corey J. Langer, MD:In the last 3 to 4 months, really since the end of 2017, theEGFRmutation field has grown and has become even more complicated. There’s a major trial, called FLAURA, that was presented at the ESMO 2017 Congress. The trial directly compared osimertinib, a third-generation TKI targetingT790M, to either frontline erlotinib or gefitinib. It’s important to note that afatinib wasn’t in the control arm of this study. Osimertinib yielded a somewhat higher response rate but significantly improved progression-free survival—about 18.9 months versus roughly 10 to 11 months in the control group.

In the minds of many of my colleagues, and to some extent myself, osimertinib has now effectively displaced gefitinib and erlotinib. It has never been directly compared with afatinib. In LUX-Lung 3, afatinib, at least in those with actionable mutations, yielded a median progression-free survival that was basically between 13 and 14 months. So, afatinib has always performed a little bit better than gefitinib and erlotinib.

This has caused some flux in the field. Afatinib still maintains an indication for treatment-naïve individuals with an actionable mutation. And, very importantly, it has an indication that is shared by none of the other agents—use with less common mutations like exon 18 and select exon 19 mutations. I anticipate a time when we will start evaluating the results of studies that are combining angiogenesis inhibitors with TKIs. One wonders whether that combination might be equal to, or, perhaps, exceed osimertinib.

So, stay tuned. In the next 12 to 24 months, I think there will be a lot more data for individuals withEGFRmutations, and I anticipate a further improvement in their therapeutic outcomes.

Transcript edited for clarity.

June 2017

• A 61-year-old Caucasian woman presented with persistent cough and shortness of breath
• Patient history:
  • Never smoked
  • Mild hypertension, controlled on diuretic
  • No major cardiovascular disease or diabetes
  • Worked at local jazz club until symptoms forced her to resign
• Physical exam and imaging:
  • No palpable masses
  • CT reveals multiple tumors in right lung and brain metastases
  • ECOG PS: 1
• Biopsy and mutation analysis:
  • Adenocarcinoma
  • EGFRexon 19 deletion
  • No ALK rearrangement
• Started treatment with afatinib 40 mg once daily
  • Developed diarrhea that necessitated dose interruption
  • Recovered and resumed treatment at 30 mg once daily

March 2018

• Patient remains on afatinib, with no apparent progression