Weiss Discusses Treatment Options in 3 Lung Cancer Cases
Published Online:4:48 PM, Mon December 19, 2016
Jared Weiss, MD
In the first case, the patient was a 65-year-old male who presented to his physician with a cough and shortness of breath. He was ultimately diagnosed with stage IV non-small cell lung cancer (NSCLC).
The patient is very active, rides his bicycle long distance for leisure, and speaks a lot for work.
MRI testing of the brain came back negative. A tissue biopsy showed EGFR-positive adenocarcinoma.
TARGETED ONCOLOGY: What treatment would you suggest giving to this patient?
Weiss: The key point of this case is the presence of an EGFR mutation. For best progression-free survival (PFS), and for best side effect profile, this patient should be treated with an EGFR tyrosine kinase inhibitor (TKI). There are 3 FDA-approved TKIs: gefitinib (Iressa), erlotinib (Tarceva), and afatinib (Gilotrif).
Any of these 3 would be reasonable for this patient. In [this] case, his physician picked gefitinib because of a lower incidence of rash and diarrhea, and his interest in riding long distances. Also, since he speaks a lot for work, he wanted to avoid rash.
The patient was treated with gefitinib. His cough and shortness of breath rapidly resolved. He experienced mild rash and mild diarrhea.
TARGETED ONCOLOGY: How would you manage these toxicities for this patient?
Weiss: For the rash, he could be given a steroid cream such as aclometasone (Aclovate), topically applied. If it’s more than mild, he could also be given an anti-inflammatory antibiotic, such as minocycline (Minocin).
The first-line approach for the diarrhea would be loperamide (Imodium) after each loose stool. If that is not adequate, more aggressive drugs such as atropine (Lomotil) or octreotide (Sandostatin) could be used by someone skilled in the use of those medicines.
After 10 months, CT imaging showed slow growth of peripheral lung nodules. This was followed on serial imaging over 4 months, at which time the pace of growth increased.
TARGETED ONCOLOGY: What is the next step for this patient now that he has progressed?
Weiss: Fifty percent or 60% of resistance to first-line EGFR TKIs, like gefitinib, are [due to] a secondary mutation called T790M. The right maneuver at this point is to re-biopsy a growing nodule and test for T790M.
The patient was started on osimertinib and his response to treatment is ongoing at 10 months.
In the second case, the patient was a 62-year-old never-smoker who presented with stage IV adenocarcinoma. An extensive immunohistochemistry workup was conducted by pathology prior to the patient meeting with their doctor. This confirmed CK7+, CK20-, TTF1+ non-small cell carcinoma. The patient was negative for many other markers.
Molecular testing was requested, but the tissue had been used up. The patient is opposed to a repeat biopsy.
TARGETED ONCOLOGY: What should be done for this patient?
Weiss: There are 2 reasonable answers. The core answer is that it is mandatory to get molecular testing, and there are 2 ways to do it. You can either do a repeat biopsy to try and get a better specimen, or you could get a liquid biopsy—plasma-based molecular testing.
A liquid biopsy was performed for the sake of molecular testing, which revealed an exon 19 EGFR mutation.
The patient was treated with erlotinib and remained on the treatment for 10 months, after which progression was noted in the central chest as well as multiple new sites of metastases.
TARGETED ONCOLOGY: The patient’s liquid testing was negative for T790M. He requested treatment with an immunotherapy he saw on TV. What should you do at this time?
Weiss: Immunotherapy would not be the most promising option for this patient. The existing data for efficacy of the immunotherapy drugs in patients with the EGFR mutation show less promise than for patients without the EGFR mutation.
The right thing to do for this patient would be a platinum-based doublet therapy.
The patient was treated with carboplatin and pemetrexed for 2 cycles. As of his first scan a minor response is noted.
In the third case, the patient was a 40-year-old male professor who was diagnosed with EGFR-mutant stage IV NSCLC.
The patient requested to be treated in the first-line setting with osimertinib (Tagrisso).
TARGETED ONCOLOGY: Would you recommend giving osimertinib to a patient like this?
Weiss: At the current time, osimertinib is not FDA approved for the first-line treatment of stage IV lung cancer, however, it is actively being studied for that indication.