Would you consider checkpoint inhibitor therapy alone in a patient with metastatic NSCLC with PDL-1 < 1% who is otherwise refusing chemotherapy?

I would not personally recommend a checkpoint inhibitor in the first line setting of a PDL1 negative metastatic NSCLC. I think genomic analysis would help guide that decision as well. For example, the presence of an STK11 mutation would make me even more hesitant to recommend a single agent checkpoi...

I would not do single agent IO.

I would consider ipilumumab+nivolumab based on Checkmate-227, where PDL1<1% and TMB-low subgroups showed benefit.

I agree with @Dr. First Last's answer. I would generally try to understand why the patient is refusing chemo (ie chemo + pembro), and reassure them about 4 cycles of chemo, then maintenance pembro; however, if after thoughtful consideration they still refuse chemo, I'd think about nivo/ipi given the...

With the available keynote data, I would not recommend pembro for PD-L1 <1%. If they have good functional status and no overt autoimmune diseases, ipi+Nivo is an option for TMB high expressers. I would also get full NGS testing, either tissue or liquid if not enough tissue is available.