Osimertinib plus consolidative radiotherapy for advanced EGFR mutant non-small cell lung cancer: a multicentre,...

Despite high response rates to epidermal growth factor receptor (EGFR) inhibitors, patients with advanced EGFR 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.

This multicentre, single-arm phase 2 trial was conducted at two sites in the USA. Eligible patients (aged ≥18 years) had advanced EGFR 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.

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.

These findings show osimertinib plus consolidative RT was well tolerated and demonstrates promising efficacy in patients with advanced EGFR 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.

AstraZeneca and the Biostatistics Shared Resource, UT Southwestern Harold C. Simmons Comprehensive Cancer Center.