What is your preferred first line approach to patients with Stage IV non-squamous NSCLC with good performance status, no driver mutations, PD-L1 low-positive, and CKD IIIB or worse, CrCl < 45 mL/min?

This is a common scenario. For patients with PD-L1 high tumors, would certainly, of course, feel comfortable with ICI monotherapy. For squamous NSCLC with PD-L1 low or negative, the question is more straightforward since taxane can be given in the setting of renal insufficiency. For nonsquamous NSCLC where we generally would offer pemetrexed therapy, this becomes more challenging.

First, I would point you to excellent and thorough discussions of chemotherapy in the setting of renal insufficiency provided by Dr. @Dr. First Last on prior questions: here and here.

The only thing I might add is we have looked at a limited series of patients from our center and found that pemetrexed can be given with caution and doe modification in select patien...