Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study

Abstract

SUMMARY BACKROUND: Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some experiencing limited disease progression (oligoprogression). We hypothesized that stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve outcomes. METHODS: We conducted a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC), defined as ≤ 5 progressive lesions on PET/CT or CT and after ≥ 1 line of systemic therapy (NCT03808662). Patients were enrolled from a tertiary cancer centre in New York City and six Tri-State regional sites, with a 1:1 randomisation between standard of care (SOC) and SBRT plus SOC. The primary endpoint was 12-month progression-free survival (PFS). FINDINGS: From January 2019 to July 2021, 106 patients were randomised – 47 with breast cancer and 59 with NSCLC. The median follow-up was 11.6 months for SOC arm and 12.1 months for SBRT arm. One-third of breast cancers were triple-negative and 86% of NSCLC had no actionable mutation. Median PFS was 3.2 months in SOC arm vs. 7.2 months in SBRT arm (p=0.002). Pre-specified subgroup analysis identified significant PFS benefit from SBRT in NSCLC (2.2 vs. 10 months; p=0.002) but not in the breast cancer (4.2 vs. 4.4 months; p=0.20). Eight patients in the SBRT arm had grade ≥ 2 toxicities related to SBRT. The study was closed to accrual before reaching the targeted 160 patients due to meeting the preplanned efficacy endpoint during an interim analysis. Changes in cell-free DNA metrics from baseline to first follow-up after SBRT suggested oligoprogression in NSCLC, distinct from the systemic progression observed in breast cancer. INTERPRETATION: The trial confirmed oligoprogression in metastatic NSCLC that could be effectively treated with SBRT, leading to a ≥ 4-fold increase in PFS compared to SOC, in contrast to breast cancer. Further studies to validate these findings and understand the striking differential benefits are warranted.