ALEX and ALUR trials demonstrate CNS efficacy with alectinib for NSCLC

By Liz Meszaros, MDLinx
Published September 14, 2017

Key Takeaways

Alectinib may significantly decrease central nervous system (CNS) progression of non-small cell lung cancer (NSCLC) when used as first- and second-line treatment, according to results from two phase 3 studies—ALUR and ALEX—presented here at the European Society for Medical Oncology (ESMO) 2017 Congress.

“This is another important goal reached in the field of thoracic oncology,” said ALUR study investigator Dr. Silvia Novello, University of Turin, Italy. “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 which has this activity on brain metastases can allow us to modify treatment and reduce the need for whole brain radiotherapy.”

Their results “support alectinib as a new standard-of-care for patients with previously treated ALK-positive NSCLC,” she added.

For this trial, Dr. Novello and colleagues included 107 ALK-positive NSCLC patients with disease progression despite first-line combination treatment of both platinum-based chemotherapy and crizotinib. They randomized patients to second-line therapy with either standard relapse chemotherapy or alectinib, and found significantly longer median progression-free survival (PFS) in patients treated with alectinib compared with chemotherapy (9.6 vs 1.4 months, respectively; HR: 0.15; 95% CI: 0.08, 0.29; P < 0.001).

Researchers observed a marked difference in CNS responses between the groups. In patients with measurable CNS disease at baseline, the CNS overall response rate (ORR) was significantly higher in patients treated with alectinib compared with chemotherapy (54.2% vs 0.0%; P < 0.001).

In addition, Dr. Novello and fellow researchers found that the safety profile of alectinib was comparable to that of chemotherapy, despite a substantially longer duration of treatment (20 vs 6 weeks, respectively).
Similarly, in a new subgroup analysis of data from the ALEX trial, researchers had previously shown significantly better PFS in treatment-naïve ALK-positive NSCLC patients treated with alectinib compared with crizotinib (HR for disease progression or death: 0.47; 95% CI: 0.34, 0.65; P < 0.001).

In this analysis, researchers included 122 patients with CNS metastases at baseline, and found that alectinib controlled existing CNS metastases as well as inhibited the formation of new metastases better than crizotinib.

“Clearly this superiority against CNS metastases contributes to the overall efficacy of alectinib,” said lead author Shirish Gadgeel, MBBS, University of Michigan, Ann Arbor, MI. “By its superior efficacy in the CNS, alectinib limits the morbidity both from these metastases but also from treatments such as whole brain radiation.”

“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, 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,” commented Prof. Fiona Blackhall, from the University of Manchester and The Christie Hospital, UK, who was not involved in either study.

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