Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non–small cell lung cancer: a multicentre, single-arm, phase 2 trial
Sagus Sampath, Sawsan Rashdan, Puneeth Iyengar, Townes A Mickel, Song Zhang, Chul Ahn, Ang Gao, Jonathan E. Dowell, Yuanyuan Zhang, Kenneth D. Westover, Suzanne Cole, Arya Amini, Adam Rock, Erminia Massarelli, Marianna Koczywas, David E. Gerber
Abstract
Background: mutant non-small cell lung cancer (NSCLC) generally experience disease progression within 2 years. We evaluated whether consolidative radiation therapy (RT) to residual sites of disease at the time of expected best response to EGFR inhibition prolongs disease control. Methods: mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; and no prior treatment with EGFR or immune checkpoint inhibitors. Patients with stable or responding disease after 8 weeks of osimertinib 80 mg orally daily received radiation therapy (RT) to persisting lesions, followed by continued osimertinib until progression or intolerance. The primary endpoint was progression-free survival (PFS) in all participants who received at least one dose of osimertinib, assessed radiographically every 8 weeks. Secondary endpoints were toxicity, duration on osimertinib, and overall survival (OS). This trial is registered with Clinicaltrials.gov, NCT03667820. Findings: Between Oct 15, 2018, and July 1, 2021, 42 patients (32 female, 10 male) were enrolled and initiated osimertinib, of whom 32 (76%) received consolidative RT, primarily stereotactic RT. The most common reasons RT was not administered were insufficient residual disease (10%) and inadequate response (5%). At a median follow-up of 35.7 months, median PFS was 32.3 months (95% CI, 21.9-51.7), median OS was 45 months (95% CI, 39.3-56.4), and median duration of osimertinib was 32.4 months. Osimertinib-related toxicities, including skin, nail, and gastrointestinal events, occurred at expected rates and were almost always grade 1-2. Two patients (5%) developed pneumonitis, including one grade 4 event. Interpretation: mutant NSCLC. Because this approach may be less complex and less toxic than multi-agent targeted therapy regimens for this population, the results of ongoing randomised trials testing similar strategies are awaited. Funding: AstraZeneca and the Biostatistics Shared Resource, UT Southwestern Harold C. Simmons Comprehensive Cancer Center.