Yes, I do treat with RET inhibitors regardless of PD-L1 status given the response rates on the order of 70-85% in treatment naive patients with selpercatinib and pralsetinib. If we look to the data of immunotherapy in other actionable oncogene driven subsets of lung cancer like EGFR mt NSCLC, the re...

For RET rearranged metastatic NSCLC, I'm using selpercatinib (now could consider pralsetinib as well) frontline irrespective of PD-L1 status. In a retrospective study, Offin et al analyzed 74 patients with NSCLC with RET-re-arrangement (61 patients with metastatic disease). 26 patients had suff...

Yes, I would use RET inhibitor first line. None - would wait for full molecular testing to determine best course of treatment.

RET fusions are typically found in patients who never smoked or very light smoking history. Treatment with immune checkpoint inhibitors, not surprisingly, are generally associated with lower efficacy and concern about rapid progression in a small case series (IMMUNOTARGET registry, Mazieres et al. P...

Despite lower efficacy to IO (Mazieres et al., PMID 31125062; Offin et al., PMID 31192313), RET-positive NSCLC seems to be sensitive to chemotherapy used in first line based on current evidence (Gautschi et al., PMID 28447912) and specifically pemetrexed-based chemotherapy (Drilon et al., PMID ...