Jaishri O. Blakeley, MD
Invited study discussant Jaishri O. Blakeley, MD, Director of the Johns Hopkins Comprehensive Neurofibromatosis Center, Baltimore, changed the title of her talk to “Finding Needles in Haystacks,” “because this is what we do with CNS [central nervous system] tumors,” she told listeners.
“ALK represents a common mutation in a rare tumor, and we see remarkable response rates when the appropriate therapy is applied to the right variant,” she continued.
“Of the seven patients with adult-onset neuroblastoma who had ALK-positive disease and were treated with ALK inhibitors, five had an objective radiographic response, and six had clinical benefit. This is great news in these heavily treated patients,” stated Dr. Blakeley. “This is a remarkable response rate and rate of clinical benefit.”
However, she cautioned, three of the seven patients had to discontinue treatment due to adverse events.
“CNS tumors are driven and maybe even dependent on targetable pathways. This and other ultra-rare tumors require dedicated molecular testing to show that a targetable variant is present. This is well worth the effort, because the objective response rate and long-term benefit can be just remarkable,” stated Dr. Blakely. “The negative side is that these drugs require continuous dosing, which can impact quality of life. That said, precision medicine is here for neuro-oncology,” she noted.
Even though next-generation sequencing is becoming more widely used, and more targetable genetic alterations are being identified, this doesn’t always translate to use of targeted therapy.
As Dr. Blakely pointed out, in one study of sequencing, actionable alterations were found in 37.6% of participants, but 17.4% received treatment based on next-generation sequencing results. Of 94 patients, 35 (37.2%) with CNS tumors were assigned to a treatment arm based on an actionable variant, and 23 of the 35 participants (65.7%) were enrolled on the desired treatment.1
Disclosure: Dr. Blakeley has served as a consultant or advisor to AbbVie, Astellas Pharma, AstraZeneca, Exelixis, and Vertex Pharmaceuticals; has received institutional research funding from Bristol Myers Squibb, GlaxoSmithKline, Lilly, and Sanofi; has been reimbursed for travel, accommodations, or other expenses by Exelixis; and has held uncompensated institutional relationships with SpringWorks Therapeutics.
1. Flaherty KT, Gray RJ, Chen AP, et al: Molecular landscape and actionable alterations in a genomically guided cancer clinical trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J Clin Oncol 38:3883-3894, 2020.
Targeting mutations appears to be bearing fruit in the treatment of some difficult-to-treat tumors. For instance, in one study of adult-onset neuroblastoma, targeting ALK mutations in ALK-positive tumors demonstrated activity, even in patients who had not responded to their first ALK inhibitor. Of...