Case Discussion: A 65-year-old Man with Stage IV NSCLC

Jared Weiss, MD:We may as well use a real-world de-identified case. The patient was in his mid-60s and was diagnosed with stage IV adenocarcinoma of the lung. He had tissue-based testing that defined the presence of a classical EGFR mutation, and he chose to enter a clinical trial that randomized patients to erlotinib or the combination of erlotinib and bevacizumab. He was randomized to the erlotinib arm and was treated with erlotinib. This was complicated by side effects of diarrhea and rash. The diarrhea was fairly easily controlled with Imodium, although it did have a small, but real, effect on his quality of life. The rash really bothered him because he lectured a lot. He had a very public presence and wearing his cancer bothered him. This was treated with minocycline and topical steroids with real efficacy, but not complete resolution.

He received erlotinib for about 10 months, at which point his cancer was progressing asymptomatically, as seen on a CAT scan. We felt, at that time, that the pace of progression was slow, and he was completely asymptomatic. So, we elected to continue erlotinib and repeat scans 3 months later. This was done, and 3 months later, the cancer was growing more rapidly. One of the spots was fairly central in a location that made me fear that if we allowed it to keep growing, he would get into trouble. We considered the approach of radiation to the spots of progression, followed by re-initiation of his erlotinib. We actually have a clinical trial that does exactly that, but it was felt that not all of his lesions were amenable to stereotactic radiosurgery—and there were a number of them. I believe there were five of them. We decided that that wasn’t the right way to go for him.

There is now an FDA-approved third-generation EGFR tyrosine kinase inhibitor called osimertinib, or its brand name, Tagrisso. This is a drug that is specifically designed to take out not only mutated EGFR, but also T790M-mutated EGFR. T790M represents about 60% of acquired resistance to the first-line agents. This agent has been studied extensively, and in most of the studies, the response rate is about two-thirds. And just like with the first-line agents, most of the patients who don’t achieve a response do have stable disease. The drug is also very tolerable. It actually has less side effects, particularly less rash and less diarrhea than the first-line agents. Patients feel very good on it, and it’s very effective. So, this patient had testing very specifically looking for the presence of T790M, with the goal of using this agent.

This patient’s case was presented at our multidisciplinary tumor board, where his most recent scan was put up on a very large screen and compared to the prior. One of the lesions that was growing was central. After discussion between the surgeon, the interventional pulmonologist, and the interventional radiologist, a decision was made that the safest and most effective way to acquire tissue for the purposes of this testing would be through bronchoscopy. That was done; it did show a T790M result, and he was treated with osimertinib.

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
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