Brain MRI surveillance needed for TKI-treated ALK or ROS1-positive NSCLC
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CHICAGO — Retrospective data showed how common central nervous system metastases are among patients with non-small cell lung cancer and ALK or ROS1 alterations who have been treated with tyrosine kinase inhibitors.
“I’m really excited about this study because it’s a collaboration between 12 sites across North America, including one in Canada,” Melina Marmarelis, MD, assistant professor of medicine at University of Pennsylvania, told Healio about a presentation from ASCO Annual Meeting. “It’s a retrospective cohort study of patients with ALK and ROS1 alterations in non-small cell lung cancer. It’s one of the biggest retrospective studies out there.”
The study collaborators came from 12 Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC) sites.
“This is a cohort of patients starting in 2003 all the way to 2021,” Marmarelis said. “This will allow us to really look at treatment patterns and the effect of sequential therapies, in particular, on things like brain metastases.”
The final analyses included 566 patients with ALK (n = 464) and ROS1 (n = 102) alterations. In the ALK group, 92% (n = 426) received a TKI at some point during therapy and 86% (n = 88) in the ROS1 group. TKI was first line therapy for 262 patients with the ALK alteration and for 48 patients with ROS1.
The most common first line TKI was crizotinib (Xalkori, Pfizer) for both ALK and ROS1 alterations, followed by alectinib (Alecensa, Genetech) for ALK and lorlatinib (Lorbrena, Pfizer) for ROS1. The second most common initial TKI was alectinib for ALK and entrectinib (Rozlytrek, Genentech) for ROS1. For patients with ALK alterations, the median follow-up time was 31.1 (95% CI, 27.6-35) months and 32.6 (95% CI, 25.7-39.6) months for patients with ROS1 alterations.
According to the abstract, the median overall survival from start of the first TKI was 53.3 months for ALK alterations (95% CI, 40-68.9) and 42 months for ROS1 alterations (95% CI, 31.8-not reached). Prior to receiving first line therapy, 321 patients had available brain imaging. Of these patients, 40% with ALK alterations, (n = 105) and 39% with ROS1 (n = 23) had CNS disease.
“We zeroed in on brain metastases for this presentation and showed that they are still very prevalent among patients with ALK and ROS1 alterations,” Marmarelis said. “In particular, with the earlier TKIs such as crizotinib, patients are more likely to develop a new brain metastasis while on treatment as opposed to some later-generation TKIs.”
Among patients without previous CNS disease, brain metastases developed at 24 months in 14.4% (95% CI, 6.1-26.1) of patients in the ALK group who received other TKI’s compared with 48.9% (95% CI, ) who received crizotinib. For patients in the ROS1 group, 47.4% (95% CI, 27.9-64.6) developed brain metastases at 24 months. Treatment discontinuation of first TKI occurred a median 11.2 months for ALK alteration and 10.8 months for ROS1.
“What this really shows is that even with later-generation TKIs, brain metastases are common and routine surveillance with brain MRIs should be included in the treatment of these patients,” Marmarelis concluded.
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Marmarelis, ME, et al. Treatment patterns and outcomes in ALK or ROS1 altered NSCLC: An ATOMIC Registry Study. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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