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First-line Osimertinib and Bevacizumab Treatment in Metastatic EGFR-Mutant Lung Cancer

By: Anna Nowogrodzki
Posted: Wednesday, August 5, 2020

The combination of osimertinib and bevacizumab in the first-line setting seems to be safe and tolerable for patients with metastatic EGFR-mutant lung cancer, according to the results of a phase I/II trial. Helena A. Yu, MD, of Memorial Sloan Kettering Cancer Center, and colleagues published their study findings in JAMA Oncology, noting a randomized phase III trial comparing the combination with osimertinib monotherapy is “moving forward.”

“The combination had promising activity against central nervous system metastases,” the authors added. “Of the six patients with measurable central nervous system disease, all had a partial or complete central nervous system response.”

The single-center study enrolled 49 patients with metastatic EGFR-mutant lung cancer between August 2016 and May 2018. Patients’ median age was 60 years, and 34 were women. Phase I of the study used a “3 + 3 dose de-escalation design.” The largest dose was tolerated and was therefore used in phase II.

In phase II, researchers gave 43 patients 80 mg of osimertinib daily and 15 mg/kg of bevacizumab every 3 weeks. The primary endpoint of phase II, 12-month progression-free survival, was 76%. The overall response rate was 80%. The median progression-free survival was 19 months. The median overall survival was not reached: 89% of patients were alive after 12 months. When analysis began on August 1, 2019, nine patients (18%) were still on study without progressive disease.

No patients had grade 5 adverse events, and the only treatment-associated grade 4 adverse event reported was proteinuria. The sole adverse event requiring treatment discontinuation was a grade 2 reduction in ejection fraction, which reversed in a patient with preexisting heart disease after discontinuing osimertinib. Thirteen patients required a dose reduction of osimertinib to 40 mg.

Disclosure: The study authors’ disclosure information may be found at jamanetwork.com.



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