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The content of this webpage has been produced in line with the LORVIQUA®▼ (lorlatinib) Summary of Product Characteristics for Great Britain.
If you are an HCP in Northern Ireland click here.
LORVIQUA®▼ (lorlatinib) Prescribing Information for Great Britain and Northern Ireland click here. XALKORI® (crizotinib) Prescribing Information for Great Britain and Northern Ireland click here. Adverse event reporting information can be found at the bottom of the page.
The CROWN study is a global, open-label, randomised, multicentre Phase 3 trial comparing the efficacy and safety of LORVIQUA® against crizotinib in treatment-naïve ALK+ advanced NSCLC patients.1,2
The primary endpoint for the CROWN study was progression-free survival (PFS)* assessed by Blinded Independent Central Review (BICR).1
Secondary endpoints included:2
The probability of PFS* at 12 months was 78% (95% CI: 70-84%) for LORVIQUA® (n=149) and 39% (95% CI: 30-48%) for crizotinib (n=147).1
Median PFS* was not reached (95% CI: NR-NR) in the LORVIQUA® arm vs. 9.3 months (95% CI: 7.6-11.1 months) in the crizotinib arm.1
LORVIQUA® reduced the risk of progression or death by 72% vs. crizotinib (HR: 0.28 [95% CI: 0.19-0.41]; p<0.001).1
Adapted from Shaw AT, et al. NEJM. 2020.1
Data cutoff: March 20, 2022.1
The probability of PFS* at 36 months was 64% for LORVIQUA® (n=149) and 19% for crizotinib (n=147).
Median PFS* was NR (95% CI: NR-NR) in the LORVIQUA® arm vs. 9.3 months (95% CI: 7.6-11.1 months) in the crizotinib arm.2
LORVIQUA® reduced the risk of progression or death by 73% vs. crizotinib (HR: 0.27 [95% CI: 0.184-0.388]).2
Adapted from Shaw AT, et al. NEJM. 2020. and Solomon BJ, et al. Lancet Respir Med. 2022.1,2
Data cutoff: September 20, 2021.2
At 36 months, the HR for PFS* by BICR favoured LORVIQUA® over crizotinib across all prespecified patient subgroups.2,3
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022. Supplementary Appendix.3
Data cutoff: September 20,2021.2
| Patients (n) | Events (n) | mPFS (months) | |
| LORVIQUA® | 37 | 16 | NR (95% CI: 18.2-NR) |
| Crizotinib | 39 | 27 | 7.2 (95% CI: 3.7-9.2) |
| HR (95% CI) | 0.21 (0.10-0.44) | ||
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
At 36 months, LORVIQUA® reduced the risk of progression or death in patients with baseline brain metastases by 79% vs. crizotinib (HR: 0.21 [95% CI: 0.10-0.44]).2
| Patients (n) | Events (n) | mPFS (months) | |
| LORVIQUA® | 112 | 33 | NR (95% CI: NR-NR) |
| Crizotinib | 108 | 65 | 11.0 (95% CI: 9.0-14.6) |
| HR (95% CI) | 0.29 (0.19-0.44) | ||
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
At 36 months, LORVIQUA® reduced the risk of progression or death in patients without baseline metastases by 71% vs. crizotinib (HR: 0.29 [95% CI: 0.19-0.44]).2
At 36 months, 92% of patients in the LORVIQUA® arm (n=149) were without IC progression vs. 38% in the crizotinib arm (n=147).
Median IC-TTP was NR (95% CI: NR-NR) in the LORVIQUA® arm vs. 16.6 months (95% CI: 11.1 months-NR) in the crizotinib arm.2
LORVIQUA® reduced the risk of IC progression by 92% vs. crizotinib (HR: 0.08 [95% CI: 0.040-0.174]).2
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
Data cutoff: September 20,2021.2
| Patients (n) | Events (n) | mIC-TTP (months) | |
| LORVIQUA® | 37 | 8 | NR (95% CI: NR-NR) |
| Crizotinib | 39 | 26 | 7.3 (95% CI: 3.7-9.3) |
| HR (95% CI) | 0.10 (0.04-0.27) | ||
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
At 36 months, LORVIQUA® reduced the risk of IC progression in patients with baseline brain metastases by 90% vs. crizotinib (HR 0.10 [95% CI: 0.04-0.27]).2
| Patients (n) | Events (n) | mIC-TTP (months) | |
| LORVIQUA® | 112 | 1 | NR (95% CI: NR-NR) |
| Crizotinib | 108 | 25 | 30.8 (95% CI: 18.4-NR) |
| HR (95% CI) | 0.02 (0.002-0.14) | ||
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
At 36 months, LORVIQUA® reduced the risk of IC progression in patients without baseline brain metastases by 98% vs. crizotinib (HR 0.02 [95% CI: 0.002-0.14]).2
At 36 months, ORR was achieved in 77% of patients treated with LORVIQUA® (n=149) vs. 59% with crizotinib (n=147). Patients in the LORVIQUA® arm were more than two times more likely to have an ORR compared to patients in the crizotinib arm (OR: 2.37 [95% CI: 1.41-4.10]). 3% of patients in the LORVIQUA® arm achieved complete response vs. 0% in the crizotinib arm.2
In patients with ≥1 measurable brain metastases at baseline, 83% achieved IC-ORR with LORVIQUA® (n=18) vs. 23% with crizotinib (n=13). Patients in the LORVIQUA® arm were more than 17 times more likely to have a IC-ORR compared to patients in the crizotinib arm (OR: 17.74 [95% CI: 2.07-173.00). 72% of patients in the LORVIQUA® arm achieved a complete response vs. 8% in the crizotinib arm.2
| LORVIQUA® | Crizotinib | |
| ITT population, n | 149 | 147 |
| Confirmed ORR by BICR, n(%) | 115 (77) | 86 (59) |
| Complete response | 4 (3) | 0 |
| Median DOR (95% CI), months | NR (NR-NR) | 9.6 (9.0-12.9) |
| Patients with measurable and non-measurable baseline brain metastases, n | 37 | 39 |
| Confirmed IC ORR by BICR, n(%) | 24 (65) | 7 (18) |
| Complete IC response | 22 (59) | 5 (13) |
| Median IC-DOR (95% CI), months | NR (NR-NR) | 9.4 (6.0-11.1) |
| Patients with measurable baseline brain metastases, n | 18 | 13 |
| Confirmed IC ORR by BIRC, n(%) | 15 (83) | 3 (23) |
| Complete IC response | 13 (72) | 1 (8) |
| Median IC-DOR (95% CI), months | NR (NR-NR) | 10.2 (9.4-11.1) |
Adapted from Solomon BJ, et al. Lancet Respir Med. 2022.2
OS was hierarchically tested for significance at the time of the interim analysis of PFS, as the primary endpoint was statistically significantly in favour of the LORVIQUA® arm.1
At the time of data cutoff for the interim analysis, OS data were still evolving, with deaths occurring in 15% of patients in the LORVIQUA® arm (n=149) vs. 19% in the crizotinib arm (n=147). LORVIQUA® reduced the risk of death vs. crizotinib by 28% (HR: 0.72 [95% CI: 0.41-1.25]), though the between-group difference in OS was not significant.1
*Defined as the time from randomisation to RECIST-defined disease progression or death from any cause.1
†At the time of the interim analysis the median follow-up for PFS was 18.3 months in the LORVIQUA arm and 14.8 months in the crizotinib arm.1
‡At the time of the updated analysis, the median duration of treatment was 33.3 months (IQR: 13.9-39.8) with LORVIQUA® and 9.6 months (IQR: 4.7-17.1) with crizotinib. Median duration of follow-up for PFS was 36.7 months (IQR: 31.3-41.9) with LORVIQUA® and 29.3 months (IQR: 10.8-35.0) with crizotinib.2
Outcomes for the secondary endpoint of patient-reported quality of life.
Safety profile of LORVIQUA® in the CROWN Study.
ALK: anaplastic lymphoma kinase, BICR: Blinded Independent Central Review, CI: confidence interval, DoR: duration of response, ECOG: Eastern Cooperative Oncology Group, HR: hazard ratio, IA: investigator-assessed, IC: intracranial, ITT: intention-to-treat, NR: not reached, NSCLC: non-small cell lung cancer, ORR: objective response rate, OS: overall survival, PFS: progression-free survival, QoL: quality of life, RECIST: Response Evaluation Criteria in Solid Tumours, TTP: time to progression, TTR: time to response.
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