Company warns about risk for severe infections with drug approved for lung, thyroid cancers
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Data from a phase 3 trial designed to compare pralsetinib with standard therapy for certain patients with advanced lung cancer revealed a risk for severe — and potentially fatal — infections with the drug, according to its manufacturer.
Pralsetinib (Gavreto, Rigel Pharmaceuticals) is an oral kinase inhibitor designed to target oncogenic RET alterations.
The agent is approved in the United States for treatment of adults with RET fusion-positive locally advanced or metastatic non-small cell lung cancer, as well as patients aged 12 years or older with locally advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy.
The ongoing randomized phase 3 AcceleRET-Lung trial is designed to evaluate pralsetinib vs. standard of care for first-line treatment of RET fusion-positive metastatic NSCLC.
Rigel Pharmaceuticals issued a “dear health care provider” letter Oct. 24 noting an ad hoc analysis “demonstrated an imbalance” in the risk for severe or fatal infections — including severe opportunistic infections — between the pralsetinib and standard-of-care groups.
An imbalance in fatal events — primarily due to infections — between the treatment groups triggered the analysis.
Fourteen patients (13%) assigned pralsetinib and five patients (4.8%) assigned standard of care had experienced fatal adverse events. Five patients (4.6%) assigned pralsetinib and none assigned standard of care experienced fatal infection events.
The letter — signed by Lisa Rojkjaer, MD, Rigel’s executive vice president and chief medical officer — noted “no clustering of any noninfectious events suggestive of a causal role of pralsetinib” had been observed.
At the time the ad hoc review took place, 212 patients had received treatment on study (pralsetinib, n = 108; standard, n = 104).
More than three times as many patients assigned pralsetinib had developed grade 3 to grade 5 infections (25.9% vs. 7.7%).
Statistical analyses revealed a “significant imbalance” in severe infection adverse events, with a RR of 3.33 (95% CI, 1.57-7.06), according to the letter.
Half of the severe infections reported in the pralsetinib group developed within 66 days of treatment, and about half of severe infections developed in the lungs.
Seven patients (6.5%) assigned pralsetinib developed severe opportunistic infections, including pneumocystis jirovecii pneumonia, cytomegalovirus pneumonia, legionella pneumonia or esophageal candidiasis. No severe opportunistic infections occurred in the standard-of-care group.
“This data supports concluding that severe infections, including opportunistic infections, warrants an update to the Product Information in Warnings and Precautions, to alert prescribers and patients of this risk,” the letter read. “The corresponding updates to the product label will be forthcoming.”
The letter encouraged prescribers to monitor patients treated with pralsetinib closely for symptoms or signs of infection, and to ensure patients are current on vaccinations. The drug should be withheld if a patient is deemed to have an active infection, resumed with dose reduction once the infection resolves, and permanently discontinued in the setting of a life-threatening infection, the letter read.
Health care providers or patients may report adverse events to Rigel Pharmaceuticals by calling (800) 983-1329 or by emailing producthelp@rigel.com. Adverse events also may be reported to the FDA online at www.fda.gov/medwatch or by calling (800) FDA-1088.
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