ESMO 2017: ALEX and ALUR Trials: Alectinib Shows CNS Benefit in ALK-Positive NSCLC


Key Points

  • ALUR included 107 ALK-positive NSCLC patients whose disease had progressed after a previous first-line combination treatment of both platinum-based chemotherapy and crizotinib.
  • ALEX included treatment-naive ALK-positive NSCLC patients who were randomized to alectinib compared to crizotinib.

Data from two separate phase III studies presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid show the particular central nervous system (CNS) activity of alectinib (Alecensa) in patients with advanced non–small cell lung cancer involving a mutation of the anaplastic lymphoma kinase gene (ALK-positive NSCLC).

Findings from the ALUR trial (Abstract 1299O_PR), as well as a secondary analysis of the ALEX trial (Abstract 1298O_PR) show alectinib can significantly decrease CNS progression of NSCLC, both in the first-line and second-line treatment settings.

“Patients with NSCLC have a high risk of CNS and brain metastases,” commented Fiona Blackhall, PhD, FRCP, of the University of Manchester and The Christie Hospital, UK. “These trials provide an important evidence base for the CNS efficacy of alectinib that can be translated to routine clinical care.”

The ALUR results “support alectinib as a new standard of care for patients with previously treated ALK-positive NSCLC,” noted the study’s investigator Silvia Novello, MD, PhD, of the University of Turin, Italy.


ALUR included 107 patients with ALK-positive NSCLC whose disease had progressed after a previous first-line combination treatment of both platinum-based chemotherapy and crizotinib. They were randomized to second-line therapy with either standard relapse chemotherapy or alectinib.

Median progression-free survival was significantly longer in the alectinib group compared to the chemotherapy group—9.6 vs 1.4 months (hazard ratio [HR] = 0.15, 95% confidence interval [CI] = 0.08–0.29; P < .001), with a marked difference in CNS response, reported Dr. Novello.

Among patients who had measurable CNS disease at baseline, the CNS overall response rate was 54.2% in those treated with alectinib compared to zero in the chemotherapy group (p < 0.001).

The safety profile of alectinib compared favorably with chemotherapy, despite the substantially longer duration of treatment for patients on alectinib (20 weeks, vs 6 weeks with chemotherapy).

“This is another important goal reached in the field of thoracic oncology,” said Dr. Novello. “ALK-positive patients represent 4% of patients with advanced NSCLC, which is the leading cause of solid cancer deaths in men and women in several countries. CNS data are extremely relevant for these patients—the brain is a frequent site of metastasis for them—and these results are important because if we’re aiming to prolong survival, we must aim to preserve their neurocognitive capacity. A drug that has this activity on brain metastases can allow us to modify treatment and reduce the need for whole-brain radiotherapy.”


Another study to be presented at the meeting, the ALEX trial, previously showed significantly better progression-free survival among treatment-naive ALK-positive NSCLC patients who were randomized to alectinib compared to crizotinib (HR for disease progression or death = 0.47, 95% CI = 0.34–0.65; P < .001).

This new subgroup analysis, focusing specifically on 122 patients who had CNS metastases at baseline, “suggests that alectinib controls existing CNS metastases and inhibits the formation of new metastases better than crizotinib,” said Shirish Gadgeel, MD, of the University of Michigan.

“Clearly this superiority against CNS metastases contributes to the overall efficacy of alectinib,” he added. “By its superior efficacy in the CNS, alectinib limits the morbidity [not only] from these metastases, but also from treatments such as whole-brain irradiation.” 


ALK-positive NSCLC was discovered only 10 years ago, and progress in identifying precision medicines has been rapid, noted Dr. Blackhall. “Early on, patients were observed to be at high risk of CNS disease, and after the discovery of the first-in-class ALK inhibitor, crizotinib [Xalkori], there has been a focus on development of next-generation ALK inhibitors with improved CNS penetration. The results of the ALUR and ALEX trials provide proof of clinically significant CNS efficacy for alectinib and indicate that CNS staging should be routine for optimal care of patients with ALK-positive lung cancer.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.