Case Discussion: A 62 year-old Never-Smoker with Stage IV Adenocarcinoma

Jared Weiss, MD:The patient was a man in his early 60s, a never-smoker, and had had tissue-based testing for EGFR mutation, which had shown an exon 19 mutation. He was treated with erlotinib. He had side effects of diarrhea and rash that were managed, and he was treated for about a year before a decision was made that a subsequent line of therapy was required. He, again, had tissue-based testing looking for T790M, and T790M was indeed present. Osimertinib was prescribed. He had less diarrhea and less rash than he did with the first-generation agent. He said that he globally felt better. He did have a response to that therapy, which is ongoing.

This patient actually had been observed for a few months that year with asymptomatic progression, but then he started to develop a little more cough and a little bit more shortness of breath. We were able to correlate it to a central lung lesion that we thought was the cause. And that was actually the lesion that was then biopsied for his T790M testing. Repeat molecular testing was prescribed. The method to acquire tissue for this was discussed at our multidisciplinary tumor board, where his old and new scans were put up on a large screen for comparison because we’re looking for a spot that’s actually growing. And a discussion ensued between myself, the interventional pulmonologist, the interventional radiologist, and the surgeon about the safest and most efficacious way to acquire tissue. We made a decision to do so by bronchoscopy. That testing was successful and revealed a T790M mutation, with no complications from the biopsy.

We prescribed osimertinib. He did still have some diarrhea and rash, but less than he had had on his first line of therapy. He did have a partial response; it was tolerated very well. One character that toxicity tables, and even maybe quality-of-life measures, don’t always get at is that global sense of well-being; that patients say, “I feel well” versus “I feel sick.” And this patient had a dramatic improvement in that global feeling of well-being. He thought that he really felt quite well on the therapy.

Weiss case 2:

A 62 year-old neversmoker with stage IV adenocarcinoma

• Mutation testing showed an EGFR exon 19 mutation
• The patient was treated with erlotinib for 1 year; he developed diarrhea and rash which was successfully managed
• After 3 months, his disease showed progression on CT; he remained without symptoms.
• He subsequently developed cough and shortness of breath, correlated to progression of a centrally located lung lesion on his follow up CT scan
• Repeat biopsy and molecular testing of the central lesion showed EGFR T790M-positivity
• He was switched to osimertinib therapy and achieved a partial response
• The patient reported dramatic improvement in his well-being