Dr Sampath on the Safety of Consolidative Radiotherapy Plus Osimertinib in Advanced EGFR-Mutant NSCLC

“Given the concerns for causing pneumonitis with concurrent osimertinib and radiation, because there have been data on that leading up to this trial, we purposely had patients hold osimertinib [during radiotherapy], and that made a big difference as far as toxicity outcomes.”

Sagus Sampath, MD, an associate clinical professor and medical director of the Department of Radiation Oncology at City of Hope, discussed the safety profile of consolidative radiotherapy administered in conjunction with osimertinib (Tagrisso) in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC), based on findings from a phase 2 trial (NCT03667820) evaluating long-term local and intracranial control outcomes.

The study sought to determine whether combining targeted therapy with local radiation could be delivered safely without compromising efficacy or increasing pulmonary toxicity. A key aspect of the study design involved holding osimertinib during thoracic radiotherapy to mitigate the risk of treatment-related pneumonitis—a well-documented concern in prior experiences with concurrent EGFR TKIs and thoracic radiation, Sampath began. As he noted, most lesions treated in the trial were thoracic or lung-based, necessitating caution when combining these modalities.

The study demonstrated that this approach was both safe and feasible, Sampath reported. The incidence of symptomatic or grade 3 or higher pneumonitis was considered acceptably low given the potential risk for pulmonary toxicity in this setting, Sampath stated. These findings suggest that temporary interruption of osimertinib during radiotherapy significantly reduces the risk of high-grade pneumonitis and maintains the therapeutic benefits of both systemic and local treatments, he summarized.

Importantly, the interruption of osimertinib during radiation did not appear to compromise efficacy outcomes, Sampath said. The data indicated that holding osimertinib during radiotherapy maintained durable disease control, including local and intracranial responses, supporting the safety and effectiveness of this combined modality approach, he emphasized. According to Sampath, these findings underscore the value of a balanced treatment strategy that mitigates toxicity without sacrificing clinical benefit.