Entrectinib has antitumor efficacy in NTRK fusion-positive tumors
medwireNews: The multikinase inhibitor entrectinib elicits systemic and intracranial responses in patients with locally advanced or metastatic solid tumors harboring NTRK fusions, including those with non-small-cell lung cancer (NSCLC), suggests a pooled analysis of three early-phase clinical trials.
Additionally, the drug has “a manageable safety profile,” presenting author Robert Doebele (University of Colorado, Aurora, USA) told delegates at the AACR Annual Meeting 2019, held in Atlanta, Georgia, USA.
He explained that entrectinib – a potent inhibitor of TRK, ROS1, and ALK with central nervous system (CNS) activity – was investigated in the phase I ALKA-372-001 and STARTRK-1 dose-escalation trials and the phase II STARTRK-2 study that used a dose of 600 mg/day. A total of 54 adult patients with NTRK fusion-positive tumors were evaluable for efficacy across the three trials (the majority drawn from STARTRK-2), of whom 10 had a diagnosis of NSCLC.
In the full cohort of patients with NTRK fusion-positive tumors, the objective response rate (ORR) was 57.4%, while it was 70.0% for those with NTRK fusion-positive NSCLC. Complete responses were observed in four and one patient, respectively, and the corresponding median durations of response were 10.4 months and not reached.
Eleven patients in the full cohort had CNS metastases at baseline, including six of the NSCLC patients, and the intracranial ORRs were 54.5% and 66.7%, respectively. The median duration of intracranial responses was 14.3 months across all patients and was not reached for those with NSCLC.
Discussing the safety profile, Doebele highlighted that most of the adverse events (AEs) were of grade 1 or 2 and were managed by dose reductions or interruptions. A total of 4.4% of participants discontinued entrectinib due to treatment-related AEs.
Anemia was the most frequently observed treatment-related AE of grade 3 or 4, at a rate of 11.8%, followed by weight gain and fatigue, at 10.3% and 7.4%, respectively. There were no grade 5 AEs that were considered related to treatment.
In conclusion, the presenter summarized that “entrectinib induced clinically meaningful, durable systemic and intracranial responses in patients with NTRK fusion-positive solid tumors.”
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