Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions
Alectinib demonstrates better CNS efficacy in ALK+ NSCLC
Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405
Key clinical point: Alectinib showed superior CNS activity and significantly delayed CNS progression over crizotinib in patients with treatment-naive anaplastic lymphoma kinase–positive non–small cell lung cancer.
Major finding: Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) and was comparable among patients with and without baseline CNS metastases or prior radiotherapy.
Study details: A phase 3 trial of 303 patients receiving alectinib (600 mg) or crizotinib (250 mg) twice daily.
Disclosures: F. Hoffman-La Roche funded the study. Dr. Gadgeel disclosed honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.
Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405
The results of the phase 3 ALEX trial provide strong rationale for the first-line use of alectinib in patients with non–small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements.
Alectinib showed robust evidence of intracranial and extracranial efficacy, not only eliciting responses in existing brain metastases but also helping prevent new ones. These results likely translate into significant improvements in quality of life, function, and survival for patients, and reduce the well-documented health economic burden associated with the development of CNS metastases.
Newer-generation ALK inhibitors, such as brigatinib and lorlatinib, also show CNS activity and are currently in phase 3 trials. It will be important to assess their effects on brain metastases to help determine their role in managing patients with ALK-positive NSCLC.
Alesha A. Thai, MD, is with the Peter MacCallum Cancer Centre in Melbourne and Benjamin J. Solomon, MD, is with the University of Melbourne. Dr. Thai disclosed no conflicts of interest. Dr. Solomon disclosed advisory board relationships with Roche-Genentech, Pfizer, Novartis, AstraZeneca, Merck, and Bristol-Myers Squibb. These comments are from their editorial (Ann Oncol. 2018 Sep 18. doi: 10.1093/annonc/mdy415).