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Entrectinib safe, effective for ROS1-positive non-small cell lung cancer
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Entrectinib shrank tumors among patients with ROS1-positive non-small cell lung cancer and generally was well tolerated, according to results from an integrated analysis presented at the International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.
Entrectinib (RXDX-101; Ignyta, Genentech) is a tyrosine kinase inhibitor of the TRKA/B/C and ROS1 proteins that can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.
Robert C. Doebele, MD, PhD, director of University of Colorado Cancer Center Thoracic Oncology Research Initiative, and colleagues assessed entrectinib among 53 patients with NSCLC with ROS1-activiating gene fusions from the phase 2 STARTRK-2, phase 1 STARTRK-1 and phase 1 ALKA trials.
Results of the integrated analysis showed entrectinib conferred an objective response rate of 77.4% (95% CI, 63.8-87.7).
Median duration of response was 24.6 months (95% CI, 11.4-34.8).
“The data look very exciting,” Doebele said in a press release. “The hope is that entrectinib could replace crizotinib [Xalkori, Pfizer] as a first-line therapy against ROS1-positive NSCLC.”
Approximately 30% to 40% of patients with ROS1-positive NSCLC have brain metastases at time of diagnosis.
Among 23 patients with cancer in their central nervous system, researchers observed an intracranial ORR of 55% (95% CI, 31.5-76.9). Median intracranial duration of response was 12.9 months (95% CI, 5.6-not reached).
Median PFS was 13.6 months (95% CI, 4.5-not reached) among those with CNS disease and 26.3 months (95% CI, 15.7-36.6) among those without.
“This trial includes generally poorer-prognosis patients than in previous trials of ROS1-directed therapies, given the high percentage of patients with brain metastases and the inclusion of patients with an ECOG performance status of two,” Doebele said. “And yet despite treating a sicker population, entrectinib results remain very competitive with those of previous trials.”
Among 355 patients evaluable for safety across the trials, researchers mostly observed grade 1 and grade 2 adverse events. Treatment-related adverse events led to dose reduction among 27.3% of patients and treatment discontinuation among 3.9%.
“These results show the potential of precision medicines to deliver tailored and effective treatment options for people with non-small cell lung cancer, including those whose tumors have spread to the central nervous system,” Sandra Horning, MD, chief medical officer and head of global product development at Genentech, said in a company-issued press release. “We are also investigating entrectinib in NTRK fusion-positive tumors across several different cancer types and look forward to presenting those results in the near future.” – by Cassie Homer
Reference:
Doebele R, et al. Abstract OA02.01. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; September 23-26, 2018; Toronto, Canada.
Disclosures: Doebele reports ownership interest in Rain Therapeutics; speakers or advisory board roles with Ariad, AstraZeneca, Bayer, Bristol-Myers Squibb, Ignyta and Takeda; research funding or honoraria from Ariad, AstraZeneca, Guardant Health, Ignyta, Pfizer, Spectrum Pharmas, Takeda and Trovagene; and intellectual property with Abbott Molecular, Rain Therapeutics and Igynta. Please see the abstract for all other authors’ relevant financial disclosures.