1. Stage IB through IIIA --> if resectable--> surgery then 4 cycles adjuvant chemo.
If margins positive--> repeat resection ( preferred) or RT
Recent updates:
Add adjuvant atezo for 1 yr after 4 cycles adjuvant chemo if PDL1= or>1% for a DFS benefit
If EGFR mutant, add osimertinib for 3 yr after 4 cycles chemo
OR if able to use neoadjuvant chemo io do 3 cycles nivo with carbo taxol--> surgery---> 6 months nivo--> OS benefit.
My take on this:
Early stage resectable, do NGS to identify EGFR/ALK mutations. If positive, plan for surgery, adjuvant chemo, and then osimertinib for 3 years. This may change once the results of the NeoADAURA trial become available. ADAURA showed a DFS benefit with 90% patients with no disease progression at 5 yr and median DFS of 5.5 yr.
If no driver mutations, and resectable do neoadjuvant nivo with carbo taxol. High rate of path CR 37% and OS benefit.
ALK mutations: ongoing trials using alectinib
2. A side note on KRAS mutated versus wild type patients: best rx available now is chemo IO even if PDL1 > 50% do not use single agent IO.
3. Seribantumab trials in those with NRG1 mutations ( rare mutations) is a HER 3 antibody ( similar to Perjeta) and has a 33% response in this population comparable to chemo. Diarrhea.
TDxd in exon 19 or 20 insertions - ongoing trials
3. IIIB/IIIC unresectable
concurrent chemo RT followed by 1 yr durva in all comers irrespective of EGFR mutation status. Although in Europe, these patients are not given durva. Ideally enroll in a clinical trial after concurrent chemo RT.
NRG Lung 004 trial: in patients with PDL1> 50% omit chemo and use concurrent IO RT followed by maintenance IO ( durva). Bottom line, this was safe. Efficacy data pending.
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