Alecensa Appears Superior to Xalkori in ALK positive NSCLC Involving the Brain

The results from two separate clinical studies comparing Alecensa® (alectinib) to Xalkori (crizotinib) presented at the European Society for Medical Oncology in Madrid demonstrate that Alecensa®  s superior in treating non small cell lung caner (NSCLC) that has spread to the brain in anaplastic lymphoma kinase (ALK) gene positive NSCLC.

Non-squamous NSCLC is the most common type of lung cancer. Approximately 7% of patients with NSCLC have a specific genetic mutation within a gene called the ALK-gene. This mutation is associated with the development and spread of cancer. Patients with this mutation are referred to as having ALK+ NSCLC.

Precision cancer medicines have recently been developed to specifically target the ALK mutations associated with the growth of lung cancer. These agents result in a decrease of growth and spread of ALK+ cancer cells. Xalkori was the first ALK+ targeted agent approved by the United States Food and Drug Administration (FDA) for the treatment of ALK+ NSCLC. Treatment with Xalkori is a standard therapeutic approach for advanced ALK+ NSCLC.  Alecensa is also an agent targeted against the ALK mutations in NSCLC. Although both agents target the ALK mutation, there are subtle distinctions in their structure, resulting in different cellular mechanisms by way they create their anti-cancer effects.

Findings from the ALUR trial1, as well as a secondary analysis of the ALEX trial2 both show Alecensa can significantly decrease CNS progression of NSCLC in both the first-line as well as the second-line treatment setting.

Doctors presented results from the ALUR clinical trial, which included 107 ALK+ NSCLC patients whose disease had progressed after a previous first-line combination treatment of both platinum-based chemotherapy and Xalkori. These patients were treated with either standard relapse chemotherapy or Alecensa and directly compared.

Among patients who had measurable CNS disease at baseline, the CNS overall response rate was 54.2% in those treated with Alecensa compared to zero for those treated with chemotherapy. Alecensa delayed cancer progression by 9.6 months compared to 1.4 months with chemotherapy.

Another study presented at the meeting, the ALEX trial3, previously showed significantly better outcomes among treatment-naive ALK-positive NSCLC patients who were treated with Alecensa compared to Xalkori. A new subgroup analysis, focusing specifically on 122 patients who had CNS metastases at baseline suggested that Alecensa controls existing CNS metastases and inhibits the formation of new metastases better than Xalkori.

Taken together the results of these trials suggest that Alecensa appears superior to Xalkori for the control of CNS metastases in patients with ALK positive NSCLC.

References:

  1. Abstracts 1299O_PR ‘Primary results from the phase III ALUR study of alectinib versus chemotherapy in previously treated ALK+ non-small-cell lung cancer (NSCLC).
  2. Abstract 1298O_PR “Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study.
  3. N Engl J Med. 2017 Jun 6. doi: 10.1056/NEJMoa1704795.

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