Cases 2 & 3: Treatment Decisions Based on Cell-Free DNA Testing

Jonathan W. Riess, MD, MS: I can think of two patients where plasma cell—free DNA was more informative, and then the other where tissue biopsy was more informative. I had a patient who was in her mid-40s and she had an EGFR exon 19 deletion, so I discussed with her afatinib versus erlotinib. We had decided to try afatinib. She was on that for about 11 months, and then she had some small pulmonary nodules that looked new, but it was nonspecific. She was asymptomatic, and we decided we’d wait a few weeks and get another scan. The following scan showed clear progression, including growth of her primary lesion in the lung, and she was developing a little more cough. We decided—at that time she was in clinic—we would send cell-free DNA from the blood. We sent that and it was negative for both the activating mutation and EGFR T790M, exon 19 deletion as well. So, that activating mutation and T790M were both negative, and we decided to get a tissue biopsy right away of the primary lesion. We had sent that off and the tissue was positive for EGFR T790M. She was placed on osimertinib and had an excellent response. She is doing very well with minimal side effects.

I had another patient who was in her late 60s who developed growth of her primary lung cancer and some other pulmonary nodules. It was clear progression. She was having some more symptoms. I started by obtaining a tissue biopsy. This was right before cell-free DNA testing was available at our institution. She had a biopsy, but the location turned out to be very difficult and there wasn’t sufficient tissue for molecular testing. At that point, we had cell-free DNA testing available. We sent that off and that was positive for EGFR T790M. So, it was tissue negative, plasma positive this time. And, in that patient, I think it was like a week before I saw her for follow-up. Osimertinib was approved by the FDA, so it was the perfect time. We put her on osimertinib and she had a fantastic response for some time.

So, that worked out well and that’s the other side. Depending on the situation, plasma cell—free DNA testing or tissue testing can be informative. But, I think the key is to try to test and find T790M positivity any way you can in order to get osimertinib for the patient. I generally start off with plasma because the patient is there in clinic. Then, if it’s positive, switch to osimertinib, especially if there’s symptomatic progression, there’s high tumor bulk, and there’s clear growth of the cancer and that the tempo is picking up. If the plasma is negative, go to tissue to try to detect T790M that way.

Riess case 3:

68-year-old woman undergoing plasma testing for EGFR T790M Mutation.

• The patient is a 68-year-old woman previously diagnosed with adenocarcinoma
• She later developed growth of her primary tumor and several pulmonary nodules.
• She complained of shortness of breath
• Biopsy tissue was insufficient for mutation testing; plasma testing showed the presence of T790M
• After being switched to osimertinib, the patient has sustained disease control