How would you approach frontline treatment of a patient with metastatic non-squamous NSCLC with ERBB2 amplification and PD-L1 > 50%?

This interesting case brings up how to separate in our work fact from fiction. We are presented with a case of a patient with metastatic non-squamous non-small cell lung cancer with a PD-L1 TPS score of 55% and ERBB2 amplification by Foundation One testing.

What is the right approach? Standard chemo/immunotherapy as per Keynote 189? Or the Impower 150 regimen adding bevacizumab to a triplet backbone as there was a signal of activity for the EGFR/ALK subset? Or should we use targeted therapy to be...

Regarding front line therapy for ERBB2/HER2 alterations for NSCLC in the era of immune checkpoint inhibition, limited data is available. The most extensive data presented is based on ERBB2 exon 20 insertion mutations rather than amplification in NSCLC. Mazieres and colleagues published on the efficacy of immune checkpoint inhibition in patients with driver alterations, and those with BRAF, MET and KRAS experienced the highest response rates. Patients with ERBB2/HER2 insertion mutations had a res...

Very erudite discussions by both @Dr. First Last and @Dr. First Last. I've very little to add. I just want to remind readers that this patient would have been eligible technically for either KN 024 or KN 189 since neither study explicitly excluded ERBB2/HER2 abnormalities, only EGFR and ALK. Clinical factors would likely govern my decision to go with either pembrolizumab alone or the combination of pembrolizumab and pem/carbo. If the metastatic burden were high and the patient highly symptomatic...