Use of stereotactic body radiation therapy (SBRT) with erlotinib for unselected patients with limited, but progressive, metastatic non-small cell cancer (NSCLC) as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high progression-free survival (PFS) and overall survival (OS), substantially greater than historical values for patients who only received systemic agents.
Patients with stage IV NSCLC who progress through first-line therapy have poor PFS and OS, most commonly failing in original sites of gross disease. Cytoreduction with SBRT may help systemic agents delay relapse. This was purpose of single arm phase II study that included patients with stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression.
After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. The PFS, OS, and other endpoints were evaluated. The study results are reported in the Journal of Clinical Oncology.
Twenty-four patients with a median age of 67 years were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated.
Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field.
Two grade 3 toxicities were radiation related. None of 13 patients tested were positive for an EGFR mutation.
In this study, the combination of erlotinib with SBRT improved OS to 20 months compared to historic 6 to 9 month survival times among erlotinib-only treated patients. The combination improved PFS from the historical 2 to 4 months to 14.7 months for similarly selected NSCLC patients.
"Technologies have developed in the last few years that have yielded game-changing, paradigm-shifting approaches, allowing us to reconsider how radiation is delivered in combination with surgery, chemotherapy, and other systemic therapies," said Dr. Robert Timmerman, Vice Chairman of Radiation Oncology at UT Southwestern Medical Center and corresponding study author.
The trial was supported by OSI Pharmaceuticals.