CROWN
First-line lorlatinib versus crizotinib in advanced ALK-positive NSCLC (CROWN)
Phase 3N = 296NCT03052608
- Population
- Advanced ALK-positive NSCLC with no previous systemic treatment for metastatic disease
- Design
- Global randomised phase 3 trial (open-label per the 2023 report) of lorlatinib 100 mg once daily versus crizotinib 250 mg twice daily; primary endpoint progression-free survival by blinded independent central review; first report was a planned interim analysis
- Primary endpoint
- PFS
- Arms
- Lorlatinib (experimental, n = 149): Lorlatinib 100 mg once daily
- Crizotinib (control, n = 147): Crizotinib 250 mg twice daily
- People
- Shaw AT, CROWN Trial Investigators
Show the numbers
| Endpoint | Analysis | Lorlatinib | Crizotinib | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (n=296)Blinded independent central review | interimShaw 2020 | 78% at 12 mo (70–84%) | 39% at 12 mo (30–48%) | HR 0.28 (95% CI 0.19–0.41)P<0.001Planned interim efficacy analysis after approximately 133 of 177 expected events; median PFS is not given in the abstract. |
| ORRAll randomised patients (n=296)Independently assessed | interimShaw 2020 | 76% (68–83%) | 58% (49–66%) | Among patients with measurable brain metastases, intracranial response was 82% (95% CI 57 to 96) with lorlatinib and 23% (5 to 54) with crizotinib; 71% of lorlatinib-treated patients had an intracranial complete response. |
| PFSAll randomised patients (n=296)Blinded independent central review | long term-updateSolomon 2023 | 64% at 3 y (55–71%) | median 9.3 months (7.6–11.1); 19% at 3 y (12–27%) | HR 0.27 (95% CI 0.18–0.39)Unplanned analysis presented descriptively (the primary endpoint was met at the planned interim analysis); median PFS with lorlatinib was not reached. Median follow-up for PFS was 36.7 months (lorlatinib) and 29.3 months (crizotinib). |
| PFSAll randomised patients (n=296)Investigator-assessed | long term-updateSolomon 2024 | 60% at 5 y (51–68%) | median 9.1 months (7.4–10.9); 8% at 5 y (3–14%) | HR 0.19 (95% CI 0.13–0.27)Post hoc analysis of investigator-assessed outcomes (the abstract states 'post hoc'); median PFS with lorlatinib was not reached (95% CI 64.3 months to not reached). Median follow-up for PFS was 60.2 months (lorlatinib) and 55.1 months (crizotinib). |
| Endpoint | Analysis | Lorlatinib | Crizotinib | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (n=296)Blinded independent central review | interimShaw 2020 | 78% at 12 mo (70–84%) | 39% at 12 mo (30–48%) | HR 0.28 (95% CI 0.19–0.41)P<0.001Planned interim efficacy analysis after approximately 133 of 177 expected events; median PFS is not given in the abstract. |
| ORRAll randomised patients (n=296)Independently assessed | interimShaw 2020 | 76% (68–83%) | 58% (49–66%) | Among patients with measurable brain metastases, intracranial response was 82% (95% CI 57 to 96) with lorlatinib and 23% (5 to 54) with crizotinib; 71% of lorlatinib-treated patients had an intracranial complete response. |
| PFSAll randomised patients (n=296)Blinded independent central review | long term-updateSolomon 2023 | 64% at 3 y (55–71%) | median 9.3 months (7.6–11.1); 19% at 3 y (12–27%) | HR 0.27 (95% CI 0.18–0.39)Unplanned analysis presented descriptively (the primary endpoint was met at the planned interim analysis); median PFS with lorlatinib was not reached. Median follow-up for PFS was 36.7 months (lorlatinib) and 29.3 months (crizotinib). |
| PFSAll randomised patients (n=296)Investigator-assessed | long term-updateSolomon 2024 | 60% at 5 y (51–68%) | median 9.1 months (7.4–10.9); 8% at 5 y (3–14%) | HR 0.19 (95% CI 0.13–0.27)Post hoc analysis of investigator-assessed outcomes (the abstract states 'post hoc'); median PFS with lorlatinib was not reached (95% CI 64.3 months to not reached). Median follow-up for PFS was 60.2 months (lorlatinib) and 55.1 months (crizotinib). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.28 | 0.19–0.41 |
| PFS | 0.27 | 0.18–0.39 |
| PFS | 0.19 | 0.13–0.27 |
- Crizotinib (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Crizotinib |
|---|---|
| 0 | 100.0% |
| 6 | 63.9% |
| 12 | 40.9% |
| 17 | 28.2% |
| 23 | 18.0% |
- Crizotinib (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Crizotinib |
|---|---|
| 0 | 100.0% |
| 6 | 63.3% |
| 11 | 43.3% |
| 17 | 27.4% |
| 23 | 17.3% |
Appears in
Sources
Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020;383(21):2018-2029.
Solomon BJ, Bauer TM, Mok TSK, Liu G, Mazieres J, de Marinis F, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354-366.
Solomon BJ, Liu G, Felip E, Mok TSK, Soo RA, Mazieres J, et al. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. 2024;42(29):3400-3409.