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NSCLC – Alectinib shows CNS benefit in two Phase-III studies

Findings from the ALUR trial1, as well as a secondary analysis of the ALEX trial2 show that the ALK-inhibitor alectinib can significantly decrease CNS progression of NSCLC, both in the first-line as well as the second-line treatment setting.
The ALUR results “support alectinib as a new standard-of-care for patients with previously treated ALK-positive NSCLC,” noted that study’s investigator Dr. Silvia Novello, from the University of Turin, Italy.

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. They were randomised to second-line therapy with either standard relapse chemotherapy or alectinib.
Median progression free survival (PFS) was significantly longer in the alectinib group compared to the chemotherapy group – 9.6 versus 1.4 months (hazard ratio (HR) 0.15, 95 % CI 0.08–0.29; p < 0.001).
Among patients who had measurable CNS disease at baseline, the CNS overall response rate (ORR) was 54.2% in those treated with alectinib compared to zero in the chemotherapy group (p < 0.001).The safety profile of alectinib compared favourably with chemotherapy.

“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.”

The ALEX trial, previously showed significantly better PFS among treatment-naive ALK-positive NSCLC patients who were randomised to alectinib compared to crizotinib. The 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 Dr. Shirish Gadgeel, from the University of Michigan, in Ann Arbor, Michigan, USA.

Both studies are going to be presented at the ESMO 2017 in Madrid.

1 Wolf J et al., 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 Gadgeel S et al., 12980_PR: Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study