1. 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)

2. 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.