Episode Details

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we continue our discussion on metastatic non-small cell lung cancer, focusing on NSCLC with driver mutations.

* The approach to treatment of a patient with widespread metastatic NSCLC (mNSCLC) is very different than a patient without distant disease, which highlights why we do what we do:

- Important to complete staging (discussed in prior episodes) to determine the extent of disease

- Important to check molecular testing (looking for mutations in the cancer cells) and IHC for tumor proportion score (TPS) helps determine treatment options

- If your molecular testing is identified in a driver mutation gene, there are targeted options for this!

*Driver mutations are predictive of response to an oral therapy and a LACK of response to immune therapy (particularly in EGFR and ALK mutated patients)

* EGFR Mutation:

- Pay attention to the types of mutation in EGFR (not all are the same):

-- Exon 19 deletion

-- Exon 19 L858R

-- Exon 21 T790M

-- Exon 20 Insertion (Osimertinib [see below] cannot be used for this mutation)

- Osimertinib is first-line standard of care for patients with EGFR

-- Used to be a second-line agent. Many patients with EGFR mutations receiving earlier generation TKIs would develop resistance and when these tumors were sequenced, they would have Exon 21 T790M mutations. Osimertinib was effective even with this mutation and had superior overall survival data compared to chemotherapy (AURA3 Trial)

--Now it is used in first-line setting for patients with EGFR mutation based on the FLAURA trial

--- In this study, patients received osimertinib as first line vs. older generation EGFR-targeting TKIs (erlotinib or gefitib) and Osimertinib had better outcomes:

---- Showed that the median OS was 38.6 months with Osi vs. 31.8 months; also improved brain penetration! 

---- Also effective in patients with metastatic disease to the brain:

----- Only 6% of patients had CNS progression with Osi vs. 15% with others

- What if a patient is on Osi and later develops new brain mets?

-- If there is progression within just the brain (and good control in other sites of the body) you can refer patient to Radiation Oncology for SRS

-- Remember, based on discussion with Dr. Osmundson in our RadOnc lectures (Episode 028), it is important to HOLD Osimertinib if patient is going to get radiation to minimize the side effects

- What is patient had progression of disease in several sites throughout the body?

-- Management is less straightforward.

-- In many of these cases, you can consider:

--- Consolidative radiation - If small amounts of disease

--- Changing therapy - I