October 6, 2022

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Lorbrena: non-small cell lung cancer death risk reduced by 72%

Lorbrena: non-small cell lung cancer death risk reduced by 72%

Lorbrena: non-small cell lung cancer death risk reduced by 72%. Recently, the US FDA announced that it has accepted the third-generation ALK inhibitor Lorlatinib (Lorlatinib, trade name Lorbrena) Supplemental New Drug Application (sNDA) for the first-line treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) patients.

Recently, the US FDA announced that it has accepted the third-generation ALK inhibitor Lorlatinib (Lorlatinib, trade name Lorbrena) Supplemental New Drug Application (sNDA) for the first-line treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) patients.

Lorbrena: non-small cell lung cancer death risk reduced by 72%  Recently, the US FDA announced that it has accepted the third-generation ALK inhibitor Lorlatinib (Lorlatinib, trade name Lorbrena) Supplemental New Drug Application (sNDA) for the first-line treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) patients.  Recently, the US FDA announced that it has accepted the third-generation ALK inhibitor Lorlatinib (Lorlatinib, trade name Lorbrena) Supplemental New Drug Application (sNDA) for the first-line treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) patients.    At the same time, the FDA also granted priority review qualifications and is expected to respond in April this year.  ▌Lung cancer with "diamond target"  Lung cancer is one of the leading causes of cancer deaths worldwide. 1.8 million people are diagnosed with lung cancer every year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all lung cancers.  Among them, about 3% to 5% of NSCLC patients will have anaplastic lymphoma kinase (ALK) rearrangement. ALK gene rearrangement occurs mostly in young patients and non-smokers or small-smokers, and most of them are lung adenocarcinoma.    ALK mutation can be said to be a "diamond mutation" in lung cancer, and the effective rate of its targeted drugs is much higher than that of patients with EGFR mutations.  Up to now, there are five targeted drugs for ALK mutations. The first generation: crizotinib; the second generation: ceritinib, aletinib, brigatinib; the third generation: lauratinib. These drugs have greatly improved the survival rate of this type of lung cancer patient population.  ▌The third generation ALK inhibitor: loratinib  Loratinib is a third-generation ALK inhibitor that is effective against almost all ALK-resistant mutations currently known. It has strong blood-brain barrier penetration and can be used to treat brain metastases. Up to 40% of ALK-positive lung cancer patients have brain metastases.  In November 2018, lauratinib was approved as a second-line treatment for patients with ALK-positive metastatic NSCLC.  As a new generation of ALK inhibitors, the advantage of loratinib is that it can target different types of ALK+ patients with the highest effective rate; moreover, it also has a good effect on patients who are resistant to all three ALK inhibitors.    ▌The risk of death is reduced by 72%! Clinical trial data is gratifying  This sNDA is the result of the pivotal Phase 3 CROWN clinical trial. CROWN is a global, randomized, phase 3 clinical trial designed to evaluate the efficacy and safety of loratinib and the first generation ALK inhibitor Crizotinib in ALK+ NSCLC patients.  The study enrolled 296 patients with newly-treated advanced ALK-positive NSCLC and randomly assigned them at a ratio of 1:1. Among them, about 1/4 of the patients (26.4%) had brain metastases at baseline.  The results of the study published in the New England Journal of Medicine last November showed:  1. Compared with the existing standard first-line therapy crizotinib, loratinib reduces the risk of disease progression or death by 72%.  2. Compared with crizotinib, the progression-free survival (PFS) of patients in the loratinib treatment group was significantly prolonged (not reached), while the crizotinib group was 9.3 months.  3. In patients with brain metastases, loratinib shows its significant advantages. At 1 year follow-up, the survival rate without central nervous system progression in the loratinib group was 96%, while that in the crizotinib group was only 60%. Loratinib reduces the risk of central nervous system progression or death by 93%!  4. Among the patients with evaluable brain metastases, 82% of the loratinib group had intracranial remission, of which 71% achieved complete intracranial remission. Only 23% of the crizotinib group achieved intracranial remission, including 1 complete remission.  Loratinib can not only significantly improve PFS in patients, but also has a higher intracranial remission rate. It is expected that the drug will be approved as a first-line treatment for ALK+ NSCLC patients, and will bring new treatment options for patients with brain metastases. 

At the same time, the FDA also granted priority review qualifications and is expected to respond in April this year.

 

▌Lung cancer with “diamond target”

Lung cancer is one of the leading causes of cancer deaths worldwide. 1.8 million people are diagnosed with lung cancer every year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all lung cancers.

Among them, about 3% to 5% of NSCLC patients will have anaplastic lymphoma kinase (ALK) rearrangement. ALK gene rearrangement occurs mostly in young patients and non-smokers or small-smokers, and most of them are lung adenocarcinoma.

 

ALK mutation can be said to be a “diamond mutation” in lung cancer, and the effective rate of its targeted drugs is much higher than that of patients with EGFR mutations.

Up to now, there are five targeted drugs for ALK mutations. The first generation: crizotinib; the second generation: ceritinib, aletinib, brigatinib; the third generation: lauratinib. These drugs have greatly improved the survival rate of this type of lung cancer patient population.

 

▌The third generation ALK inhibitor: loratinib

Loratinib is a third-generation ALK inhibitor that is effective against almost all ALK-resistant mutations currently known. It has strong blood-brain barrier penetration and can be used to treat brain metastases. Up to 40% of ALK-positive lung cancer patients have brain metastases.

In November 2018, lauratinib was approved as a second-line treatment for patients with ALK-positive metastatic NSCLC.

As a new generation of ALK inhibitors, the advantage of loratinib is that it can target different types of ALK+ patients with the highest effective rate; moreover, it also has a good effect on patients who are resistant to all three ALK inhibitors.

 

▌The risk of death is reduced by 72%! Clinical trial data is gratifying

This sNDA is the result of the pivotal Phase 3 CROWN clinical trial. CROWN is a global, randomized, phase 3 clinical trial designed to evaluate the efficacy and safety of loratinib and the first generation ALK inhibitor Crizotinib in ALK+ NSCLC patients.

The study enrolled 296 patients with newly-treated advanced ALK-positive NSCLC and randomly assigned them at a ratio of 1:1. Among them, about 1/4 of the patients (26.4%) had brain metastases at baseline.

The results of the study published in the New England Journal of Medicine last November showed:

1. Compared with the existing standard first-line therapy crizotinib, loratinib reduces the risk of disease progression or death by 72%.

2. Compared with crizotinib, the progression-free survival (PFS) of patients in the loratinib treatment group was significantly prolonged (not reached), while the crizotinib group was 9.3 months.

3. In patients with brain metastases, loratinib shows its significant advantages. At 1 year follow-up, the survival rate without central nervous system progression in the loratinib group was 96%, while that in the crizotinib group was only 60%. Loratinib reduces the risk of central nervous system progression or death by 93%!

4. Among the patients with evaluable brain metastases, 82% of the loratinib group had intracranial remission, of which 71% achieved complete intracranial remission. Only 23% of the crizotinib group achieved intracranial remission, including 1 complete remission.

Loratinib can not only significantly improve PFS in patients, but also has a higher intracranial remission rate. It is expected that the drug will be approved as a first-line treatment for ALK+ NSCLC patients, and will bring new treatment options for patients with brain metastases.

 

(source:internet, reference only)


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