How do you manage maintenance therapy in metastatic NSCLC, adenocarcinoma with good response to initial chemo (carboplatin, pemetrexed, pembrolizumab) with borderline renal function that has worsened during initial treatment?

This is a difficult situation as it may not be possible to discern if creatinine elevation is related to pemetrexed versus immune checkpoint inhibitor (ICI)-nephritis; therefore, nephrology assessment would be crucial.

I assume the question is regarding patients with significant renal impairment (i.e. CrCl < 45 mL/minute). For this scenario, holding pemetrexed would be the safest choice based on the package insert. Decision regarding pembrolizumab would depend on the severity of renal impairment. If Cr is more than 2-3x above baseline; pembrolizumab needs to be held as ICI-nephritis cannot be ruled out (Brahmer et al., PMID 29442540). If renal impairment is less severe, pembrolizumab can be continued, while ruling out alternative etiologies,...