advanced lung adenocarcinoma subtype PD-L1 <50% EGFR or ALK or ROS1 positive [~20%] TKI 1st line PD-L1 <50% EGFR, ALK, ROS1 neg. [~50%] cytotoxic chemotherapy 1st line PD-L1 ≥50% EGFR, ALK, ROS1 neg. [~30%] anti-PD-1 pembrolizumab 1st line B advanced lung adenocarcinoma subtype 1st line therapy 2nd line therapy 3rd line therapy classic driver oncogene enriched (EGFR/ALK/ROS1 pos.) approved matched TKI approved TKI (EGFR-T790M+ or ALK) or cytotoxic chemotherapy (EGFR-T790M- or ROS1) cytotoxic chemotherapy or anti-PD-1 or anti-PD-L1 or BSC immune checkpoint inhibitor (PD-L1 TPS ≥50%) anti-PD-1 (pembrolizumab) non-oncogene non-immune (EGFR/ALK/ROS1 neg., PD-L1 TPS <50%) (+/- bevacizumab) anti-PD-1 (nivolumab or pembrolizumab) or anti-PD-L1 (atezolizumab)

Supplementary Figure 1. Separation of lung adenocarcinomas in different subgroups by driver oncogene status and PD-L1 IHC TPS. A. Graphic pie chart representation of the reported frequency of driver oncogene mutations (EGFR, or ALK, or ROS1) with approved therapies, PD-L1 tumor proportion score (TPS) of ≥50%, and biomarker negative status. B. Systemic therapy options available based on the presence of driver oncogene mutations (EGFR, or ALK, or ROS1) with approved therapies or PD-L1 TPS of ≥50% using clone 22C3. BSC, best supportive care.