Table 2.

Composition of the patient population in subgroups stratified by underlying PD-L1 expression and TMB level, and first-line treatment for each strategy

PD-L1	TMB	1L Treatment	PFS-HRa	Percentage of each subgroup constituting the population per strategyb
				A: PD-L1 alone	B: TMB alone	C: PD-L1 and TMB	D: PD-L1 + DB	E: TMB + DB	F: PD-L1 and TMB + DB
PD-L1 high	TMB high	Pembro	0.375	8.75	8.75	8.75	6.39	6.39	6.39
	TMB high	Pembro+ChT	0.270	0.00	0.00	0.00	2.36	2.36	2.36
	TMB low	Pembro	0.635	16.25	0.00	0.00	11.86	0.00	0.00
	TMB low	Pembro+ChT	0.457	0.00	16.25	16.25	4.39	16.25	16.25
PD-L1 intermediate	TMB high	Pembro	0.750	0.00	10.15	0.00	0.00	7.41	0.00
	TMB high	Pembro+ChT	0.413	10.15	0.00	10.15	10.15	2.74	10.15
	TMB low	Pembro	1.270	0.00	0.00	0.00	0.00	0.00	0.00
	TMB low	Pembro+ChT	0.699	18.85	18.85	18.85	18.85	18.85	18.85
PD-L1 low	TMB high	Pembro	1.266	0.00	16.10	0.00	0.00	11.75	0.00
	TMB high	Pembro+ChT	0.563	16.10	0.00	16.10	16.10	4.35	16.10
	TMB low	Pembro	1.786	0.00	0.00	0.00	0.00	0.00	0.00
	TMB low	Pembro+ChT	0.770	29.99	29.99	29.99	29.99	29.99	29.99
Total percentage of Pembro				25.00	35.00	8.75	18.25	25.55	6.39
Total percentage of Pembro+ChT				75.00	65.00	91.25	81.75	74.45	93.61

1L first-line, ChT chemotherapy, DB disease burden, Pembro pembrolizumab, Pembro+ChT pembrolizumab with chemotherapy (here assumed ChT as cisplatin-pemetrexed), PD-L1 programmed death-ligand 1, PFS-HR progression-free hazard ratio of 1L treatment compared to ChT, TMB tumor mutational burden

^aPFS-HR values were computed assuming independent predictive values of TMB and PD-L1 on treatment benefit [8, 18, 20] (details are given in Sect. 1.2 of the ESM)

^bPercentage depends on the prevalence of the biomarker used in the treatment choice (i.e., PD-L1 and TMB) and the percentage of patients with high tumor/disease burden