ALEX: trial | Bending the Curve: Trial by Trial

ALEX

Alectinib versus crizotinib in untreated ALK-positive advanced NSCLC (ALEX)

Phase 3N = 303NCT02075840

Population

Previously untreated advanced (stage III/IV) ALK-positive NSCLC

Design

Randomised, open-label phase 3 trial of alectinib 600 mg twice daily versus crizotinib 250 mg twice daily; primary endpoint investigator-assessed progression-free survival; included patients with asymptomatic CNS disease

Primary endpoint

PFS

Arms

Alectinib (experimental, n = 152): Alectinib 600 mg twice daily
Crizotinib (control, n = 151): Crizotinib 250 mg twice daily

People

Peters S, ALEX Trial Investigators

PFSHR 0.47 (95% CI 0.34–0.65)Δ 12-month PFS+19.7 pointsPFSHR 0.43 (95% CI 0.32–0.58)Δ median PFS+23.9 monthsOSHR 0.67 (95% CI 0.46–0.98)Δ 60-month OS+17 points

Show the numbers

Results reported for ALEX
Endpoint	Analysis	Alectinib	Crizotinib	Effect
PFSAll randomised patients (n=303)Investigator-assessed	primaryPeters 2017	68.4% at 12 mo (61.0–75.9%)	48.7% at 12 mo (40.4–56.9%)	HR 0.47 (95% CI 0.34–0.65)P<0.001The abstract calls this the 12-month event-free survival rate for investigator-assessed PFS. Median follow-up was 17.6 months with crizotinib and 18.6 months with alectinib; the median PFS with alectinib was not reached at this analysis.
PFSAll randomised patients (n=303)Investigator-assessed	finalMok 2020	median 34.8 months	median 10.9 months	HR 0.43 (95% CI 0.32–0.58)The paper titles this the final progression-free survival analysis.
OSAll randomised patients (n=303)	long term-updateMok 2020	62.5% at 5 y (54.3–70.8%)	45.5% at 5 y (33.6–57.4%)	HR 0.67 (95% CI 0.46–0.98)Overall survival data were immature (37% of events); median OS was not reached with alectinib and was 57.4 months with crizotinib. The paper presents this as updated overall survival (cut-off 29 November 2019).
OSAll randomised patients (n=303)	finalPeters 2026	median 81.1 months	median 54.2 months (34.6–75.6)	HR 0.78 (95% CI 0.56–1.08)The 95% confidence interval for the alectinib median is 62.3 months to not estimable (upper bound cannot be stored). Median follow-up was 53.5 months with alectinib and 23.3 months with crizotinib. The abstract describes this as the final overall survival analysis; no P value is given.

Results reported for ALEX
Endpoint	Analysis	Alectinib	Crizotinib	Effect
PFSAll randomised patients (n=303)Investigator-assessed	primaryPeters 2017	68.4% at 12 mo (61.0–75.9%)	48.7% at 12 mo (40.4–56.9%)	HR 0.47 (95% CI 0.34–0.65)P<0.001The abstract calls this the 12-month event-free survival rate for investigator-assessed PFS. Median follow-up was 17.6 months with crizotinib and 18.6 months with alectinib; the median PFS with alectinib was not reached at this analysis.
PFSAll randomised patients (n=303)Investigator-assessed	finalMok 2020	median 34.8 months	median 10.9 months	HR 0.43 (95% CI 0.32–0.58)The paper titles this the final progression-free survival analysis.
OSAll randomised patients (n=303)	long term-updateMok 2020	62.5% at 5 y (54.3–70.8%)	45.5% at 5 y (33.6–57.4%)	HR 0.67 (95% CI 0.46–0.98)Overall survival data were immature (37% of events); median OS was not reached with alectinib and was 57.4 months with crizotinib. The paper presents this as updated overall survival (cut-off 29 November 2019).
OSAll randomised patients (n=303)	finalPeters 2026	median 81.1 months	median 54.2 months (34.6–75.6)	HR 0.78 (95% CI 0.56–1.08)The 95% confidence interval for the alectinib median is 62.3 months to not estimable (upper bound cannot be stored). Median follow-up was 53.5 months with alectinib and 23.3 months with crizotinib. The abstract describes this as the final overall survival analysis; no P value is given.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.47	0.34–0.65
PFS	0.43	0.32–0.58
OS	0.67	0.46–0.98
OS	0.78	0.56–1.08

Illustrative — modelled from reported values, not trial data. PFS, final.

Show curves

Alectinib (experimental)
Crizotinib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Alectinib	Crizotinib
0	100.0%	100.0%
22	64.5%	24.7%
44	41.6%	6.1%
65	27.4%	1.6%
87	17.7%	0.4%

Illustrative — modelled from reported values, not trial data. OS, final.

Show curves

Alectinib (experimental)
Crizotinib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Alectinib	Crizotinib
0	100.0%	100.0%
51	64.7%	52.1%
101	42.2%	27.5%
152	27.3%	14.3%
203	17.6%	7.5%

Appears in

2017 ALEX: alectinib vs crizotinib first-line

Sources

Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(9):829-838.
PubMed DOI
Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064.
PubMed DOI
Peters S, Camidge R, Dziadziuszko R, Gadgeel S, Shaw AT, Kim DW, et al. Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study. Ann Oncol. 2026;37(1):92-103.
PubMed DOI