Table 4.

Summary of clinical trials and observational studies that have examined the prognostic association between the VeriStrat test in advanced NSCLC (stage IIIb/IV, progressive/recurrent disease) and outcomes, including TOPICAL.

						Hazard ratio for Good vs Poor (95% CI)a
Reference (first author)	Treatment	Line of therapy	Number patients	% with PS 2	% with VeriStrat ‘Good’	Overall survival	Progression-free survival
Randomised clinical trials
Carbone 2012 [10]	Erlotinib vs placebo	Second/third	436	33 (PS 2–3)	61	0.67 (0.45–1.01)b	0.56 (0.40–0.80)b
						10.5 vs 4.0 monthsc	3.7 vs 1.8 monthsc
Peters 2007 [11]	Erlotinib vs docetaxel	Second	80e	9	72	0.49 (0.28–0.86)#	0.73 (0.44–1.22)#
Stinchcombe 2013 [12]	Gemcitabine vs erlotinib vs both	First	98	28	64	0.53 (0.32–0.90)	0.51 (0.30–0.86)
Gregorc 2014 [13]	Erlotinib vs pemetrexed or docetaxel	Second	263	6	70	0.53 (0.35–0.80)	0.57 (0.44–0.75)#
Gadgeel 2017 [14]	Erlotinib vs afatinib	Second	675	0.3	61	0.41 (0.35–0.49)	0.65 (0.54–0.77)
Spigel 2018 [15]	Erlotinib vs placebo (all had pazopanib)	Second/third	88	14	72	0.42 (0.26–0.69)#	0.44 (0.26–0.73)#
Buttigliero 2019 [16]	Tivantinib vs placebo (all had erlotinib)	Second/third	996	0.2	72	Tiva: 0.33 (0.26–0.42)# Plac: 0.45 (0.35–0.58)#	0.52 (0.40–0.67)
TOPICAL trial	Erlotinib vs placebo	First	527	56% (plus 27% PS 3)	55	0.58 (0.48–0.70)	0.67 (0.56–0.81)
Single-arm clinical trials
Taguchi 2007 [9]	Erlotinib	First	96	26	72	0.53 (0.30–0.94)	0.53 (0.33–0.85)#
Amann 2010 [17]	Erlotinib	First	88	25	73	0.44 (0.18–1.08)	0.51 (0.28–0.90)#
Carbone 2010 [18]	Erlotinib + bevacizumab	Second	34	0	76	0.14 (0.03–0.58)#	0.04 (0.01–0.24)#
Dingemans 2012 [19]	Sorafenib	≥1 prior line	55f	5	58	0.77 (0.59–1.11)#	0.71 (0.53–1.0)#
Kuiper 2012 [20]	Erlotinib + sorafenib	First	50	0	66	0.30 (0.12–0.74)#	0.40 (0.17–0.94)#
Akerley 2013 [21]	Erlotinib + bevacizumab	First	41	0	76	16.5 vs 4.6 monthsd	4.4 vs 1.4 monthsd
Gautschi 2013 [22]	Erlotinib + bevacizumab	First	114	5	76	0.48 (0.29–0.78)#	0.77 (0.48–1.22)#
Observational studies
Taguchi 2007 [9]	Gefitinib	≥ second	67	24	58	0.74 (0.55–0.99)	0.56 (0.28–0.89)#
Lazzari 2012 [23]	Gefitinib	≥1 prior line	108	18	69	0.44 (0.26–0.72)	0.52 (0.30–0.92)
Grossi 2016 [24]	Pemetrexed + platinum	First	76	3	66	0.23 (0.11–0.46)	0.39 (0.22–0.71)

ECOG, Eastern Cooperative Oncology Group; CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; OS, overall survival; PS, performance status.

None of the studies except Carbone 2012 and TOPICAL included patients with PS 3.

^aAdjusted HRs (for various patient/tumour characteristics), except where indicated by # which are unadjusted HRs.

^bPlacebo group only.

^cMedian OS (or PFS) among patients with Good vs Poor VeriStrat, all received erlotinib.

^dMedian OS (or PFS) among patients with Good vs Poor VeriStrat.

^eNot EGFR positive.

^fAll had KRAS mutant tumours.