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| Molecular Profile | ALK rearrange |
| Therapy | Lorlatinib |
| Indication/Tumor Type | lung non-small cell carcinoma |
| Response Type | sensitive |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase Ib/II | Actionable | In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate (ORR) of 82.4% (14/17, all partial responses (PR)) and 63.6% (21/33, all PR) in Asian and non-Asian patients with ALK-positive non-small cell lung cancer who had prior Xalkori (crizotinib) treatment and an ORR of 47.2% (25/53, 2 complete responses, 23 PR) and 30.1% (22/73, all PR) in patients previously treated with any second-generation ALK inhibitor (PMID: 35660971; NCT01970865). | 35660971 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). | 29074098 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). | 30596843 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase II | Actionable | In a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an intracranial disease control rate of 95% (21/22), intracranial objective response rate of 59% (13/22; 6 complete responses, 7 partial responses), a median intracranial progression-free survival (PFS) rate of 24.6 months, and a 12-month PFS rate of 79% in patients with ALK-rearranged non-small cell lung cancer, who previously demonstrated central nervous system progression on second-generation ALK inhibitors (PMID: 35584349; NCT02927340). | 35584349 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase III | Actionable | In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608). | 38819031 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 30285222; ESMO.org). | 30285222 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608). | 33207094 detail... detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). | detail... detail... 30413378 |
| PubMed Id | Reference Title | Details |
|---|---|---|
| (29074098) | Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. | Full reference... |
| NCCN.org | Full reference... | |
| (30413378) | Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. | Full reference... |
| (30596843) | Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. | Full reference... |
| ESMO Clinical Practice Guidelines | Full reference... | |
| ESMO Clinical Practice Guidelines | Full reference... | |
| Full reference... | ||
| Full reference... | ||
| Lorbrena (lorlatinib) FDA Drug Label | Full reference... | |
| Lorbrena (lorlatinib) FDA Drug Label | Full reference... | |
| (33207094) | First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. | Full reference... |
| (35584349) | Phase II Study of Lorlatinib in Patients With Anaplastic Lymphoma Kinase-Positive Lung Cancer and CNS-Specific Relapse. | Full reference... |
| (30285222) | Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | Full reference... |
| (35660971) | Efficacy and safety of lorlatinib in Asian and non-Asian patients with ALK-positive advanced non-small cell lung cancer: Subgroup analysis of a global phase 2 trial. | Full reference... |
| (38819031) | Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. | Full reference... |