Table 3.

Comparison of first-line phase III trials in advanced ALK-rearranged NSCLC patients.

	PROFILE 1014 [3]		ALEX [11]		ALTA-1L [12]		eXalt3 [13]		ASCEND-4 [15]		CROWN [22]
	Crizotinib	Chemotherapy	Alectinib	Crizotinib	Brigatinib	Crizotinib	Ensartinib	Crizotinib	Ceritinib	Chemotherapy	Lorlatinib	Crizotinib
ORR	74%	45%	83%	76%	74%	62%	74%	67%	72.5%	26.7%	76%	58%
mPFS (months)	10.9	7	34.8	10.9	29.4	9.2	25.8	12.7	16·6	8.1	NR	9.3
PFS HR	0.45; 95% CI, 0.35–0.60		0.43; 95% CI 0.32–0.48		0.43; 95% CI, 0.31–0.61		0.51; 95% CI, 0.35–0.72		0·55; 95% CI 0·42–0·73		0.28; 95% CI, 0.19–0.41
Intracranial response rate	-	-	81%	50%	78%	26%	63.6%	21.1%	72·7%	27.3%	82%	23%
Frequency of dose reduction	-	-	20%	20%	38%	25%	24%	20%	80%	45%	21%	15%
Frequency of discontinuation	12%	14%	15%	15%	13%	9%	9%	7%	5%	11%	7%	9%
Key adverse events	dision disorders, diarrhea, nausea, and edema	nausea, fatigue, vomiting, and decreased appetite	myalgia, increased blood bilirubin, increased ALT	nausea, diarrhea, and vomiting	ILD/pneumonitis, nausea, CPK increase, ALT increase, lipase increase	nausea, diarrhea, edema	Rash, pruritus, nausea, pyrexia, ALT and AST increase	liver toxic effects, nausea, edema, and constipation	diarrhea, nausea, vomiting, AST and ALT increase	nausea, vomiting and anemia	Edema, Hypercholesterolemia, hypertriglyceridemia, increased weight, neuropathy, cognitive effects, speech effects	Diarrhea, vision disorder, vomiting, increased alanine aminotransferase level, fatigue, constipation, increased aspartate aminotransferase level, decreased appetite, dysgeusia, and bradycardia

ORR, objective response rate; PFS, progression-free survival; NR, not reached; CNS, central nervous system; HR, hazard ratio; CI, confidence interval.