PROFILE 1014: trial | Bending the Curve: Trial by Trial

PROFILE 1014

First-line crizotinib versus pemetrexed-platinum chemotherapy in ALK-positive nonsquamous NSCLC (PROFILE 1014)

Population

Advanced ALK-positive nonsquamous NSCLC with no previous systemic treatment for advanced disease

Design

Open-label phase 3 trial; crossover to crizotinib after progression permitted for chemotherapy patients; primary endpoint progression-free survival by independent radiologic review

Primary endpoint

PFS

Arms

Crizotinib (experimental): Crizotinib 250 mg twice daily
Pemetrexed plus platinum (control): Pemetrexed 500 mg per square metre plus cisplatin 75 mg per square metre or carboplatin (AUC 5 to 6) every 3 weeks, up to six cycles

People

Solomon BJ, PROFILE 1014 Investigators

PFSHR 0.45 (95% CI 0.35–0.60)Δ median PFS+3.9 monthsΔ ORR+29 pointsOSHR 0.82 (95% CI 0.54–1.26)Δ 12-month OS+5 points

Show the numbers

Results reported for PROFILE 1014
Endpoint	Analysis	Crizotinib	Pemetrexed plus platinum	Effect
PFSAll randomised patients (n=343)Independent radiologic review	primarySolomon 2014	median 10.9 months	median 7 months	HR 0.45 (95% CI 0.35–0.60)P<0.001
ORRAll randomised patients (n=343)	primarySolomon 2014	74%	45%	P<0.001
OSAll randomised patients (n=343)	interimSolomon 2014	84% at 12 mo	79% at 12 mo	HR 0.82 (95% CI 0.54–1.26)P=0.36Median overall survival was not reached in either group; crossover to crizotinib was permitted. The abstract does not name the OS analysis type; labelled 'interim' because a separate paper reports the final OS analysis of PROFILE 1014 (Solomon et al., J Clin Oncol 2018, PMID 29768118, not recorded here).

Results reported for PROFILE 1014
Endpoint	Analysis	Crizotinib	Pemetrexed plus platinum	Effect
PFSAll randomised patients (n=343)Independent radiologic review	primarySolomon 2014	median 10.9 months	median 7 months	HR 0.45 (95% CI 0.35–0.60)P<0.001
ORRAll randomised patients (n=343)	primarySolomon 2014	74%	45%	P<0.001
OSAll randomised patients (n=343)	interimSolomon 2014	84% at 12 mo	79% at 12 mo	HR 0.82 (95% CI 0.54–1.26)P=0.36Median overall survival was not reached in either group; crossover to crizotinib was permitted. The abstract does not name the OS analysis type; labelled 'interim' because a separate paper reports the final OS analysis of PROFILE 1014 (Solomon et al., J Clin Oncol 2018, PMID 29768118, not recorded here).

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

Data table

Endpoint	HR	95% CI
PFS	0.45	0.35–0.6
OS	0.82	0.54–1.26

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

Show curves

Crizotinib (experimental)
Pemetrexed plus platinum (control)

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

Data table (modelled values)

Months	Crizotinib	Pemetrexed plus platinum
0	100.0%	100.0%
7	64.1%	50.0%
14	41.1%	25.0%
20	28.0%	13.8%
27	18.0%	6.9%

Appears in

2010 Crizotinib for ALK-positive lung cancer (2010-2014)

Sources

Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-77.
PubMed DOI