2O - Phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR mutant non-small cell lung cancer (NSCLC): Analysis of adverse events (AEs)

Background

Most patients with EGFR mutant NSCLC who have an initial response to OSI exhibit persistent residual disease that may enable emergence of acquired resistance. Eliminating residual disease with LCT may delay resistance and improve clinical outcomes. Safety of OSI with LCT, however, is not well defined. Here we report safety data from a multicenter randomized phase II study of OSI with or without LCT for patients with EGFR mutant NSCLC.

Methods

Metastatic NSCLC patients with tyrosine kinase inhibitor naïve EGFR mutation (L858R/Exon 19 deletion) or T790M resistance mutation after prior therapy received 6–12 weeks of induction OSI. Patients without progression per RECIST 1.1 were randomized to OSI alone vs LCT plus OSI until progression. Primary objective was progression free survival. Secondary objective was safety. Patients were evaluated every 8 weeks using CTCAE v4.0. All possible, probable, and definite treatment related AEs were analyzed.

Results

From 2018 to 2022, 122 patients (median age: 65, range: 30–88) were randomized (63 to OSI alone; 59 to OSI plus LCT). Among 59 patients who received LCT, 35 (59%) received RT alone, 17 (29%) received surgery alone, and 7 (12%) received both RT and surgery. At median follow up of 16 months (range: 2–49), there were no grade 4/5 AEs. There was no significant difference in grade 3 AEs between OSI alone and OSI plus LCT (16% vs 29%; p = 0.08). The most common grade 3 AEs with OSI alone were hyponatremia (4.8%), transaminitis (4.8%), and pneumonitis (3.4%). The most common grade 3 AEs with OSI plus LCT were hyponatremia (6.8%), diarrhea (3.4%), empyema (3.4%), and pneumonitis (1.7%). Among 42 patients that received RT, 1 (2%) had a grade 3 AE possibly related to RT (non-cardiac chest pain). Among 24 surgical patients, 3 (13%) had surgery related grade 3 AEs (1 arterial injury, 2 empyema). Common grade 1–2 AEs with OSI plus LCT were fatigue (56%), diarrhea (45%), dyspnea (31%), cough (29%), pneumonitis (10%), dysphagia (12%), and esophagitis (7%).

Conclusions

OSI plus LCT is well tolerated in EGFR mutated metastatic NSCLC patients without significant increase in serious AEs compared to OSI alone.

Clinical trial identification

NCT03410043.

Legal entity responsible for the study

The University of Texas MD Anderson Cancer Center.

Funding

National Comprehensive Cancer Network (NCCN).

Disclosure

S.J. Gandhi: Financial Interests, Institutional, Research Grant: Nanobiotix Inc, BMS, Gateway Foundation.