# PROFILE 1014

Source: https://onco.cc/trials/profile-1014/  
OnCo record `profile-1014` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The trial that made an ALK pill, rather than chemotherapy, the first treatment for ALK-positive lung cancer.

## Summary

Crizotinib had been approved in 2011 on single-arm response data and confirmed against second-line chemotherapy in PROFILE 1007, but whether it should come before chemotherapy was unknown. PROFILE 1014 randomised 343 patients with untreated advanced ALK-positive non-squamous disease to crizotinib 250 mg twice daily or to pemetrexed with cisplatin or carboplatin every three weeks for up to six cycles, with crossover to crizotinib permitted at progression.

Median progression-free survival by independent radiological review was 10.9 months with crizotinib against 7.0 months with chemotherapy (hazard ratio 0.45, 95 percent confidence interval 0.35 to 0.60).

PROFILE 1014 is now historical as a treatment recommendation: ALEX, ALTA-1L and CROWN each beat crizotinib with a later-generation inhibitor, and the brain, where crizotinib penetrates poorly, is where they win. Its importance is as the first demonstration that targeting the fusion beats chemotherapy from the start, the template every later fusion programme followed.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-25
- Registry id: NCT01154140
- Phase: 3
- Setting: Untreated advanced ALK-positive non-squamous non-small-cell lung cancer: crizotinib 250 mg twice daily versus pemetrexed with cisplatin or carboplatin for up to six cycles, with progression-free survival by independent radiological review as the primary endpoint and crossover allowed
- Sponsor: Pfizer
- Enrolled: 343
- Result: Median progression-free survival 10.9 against 7.0 months (hazard ratio 0.45, 95 percent confidence interval 0.35 to 0.60).
- Outcomes: Progression-free survival (independent radiological review): Crizotinib 10.9 months vs Pemetrexed and platinum 7 months, HR 0.45
- Replication: Superseded rather than replicated: ALEX (alectinib), ALTA-1L (brigatinib), ALESIA (alectinib in Asia) and CROWN (lorlatinib) all used crizotinib as the control and beat it.

## Sources

- ClinicalTrials.gov NCT01154140: https://clinicaltrials.gov/study/NCT01154140
- PROFILE 1014 (New England Journal of Medicine 2014): https://doi.org/10.1056/NEJMoa1408440

## Connected records

- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Platinum agents](https://onco.cc/technologies/platinum/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/)
- drugs: [Alectinib](https://onco.cc/drugs/alectinib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- trials: [ALESIA](https://onco.cc/trials/alesia/), [ALEX](https://onco.cc/trials/alex/), [ALTA-1L](https://onco.cc/trials/alta-1l/), [CROWN](https://onco.cc/trials/crown/), [J-ALEX](https://onco.cc/trials/j-alex/)

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