Use of consolidative stereotactic ablative radiotherapy (SAbR) prior to maintenance chemotherapy improves progression-free survival (PFS) by more than 6 months in patients with non-small-cell lung cancer (NSCLC) who have limited metastases, a recent phase II study has shown. [ASTRO 2017, abstract LBA3; JAMA Oncol 2017, doi: 10.1001/jamaoncol.2017.3501]

In this study, 29 NSCLC patients with limited metastases (defined as up to five metastatic sites) were randomized to receive SAbR followed by maintenance chemotherapy (n=14), or maintenance chemotherapy alone (n=15). The primary endpoint was PFS. Secondary endpoints included overall survival (OS), tolerability, local and distant tumour control, and patterns of progression.

“Previous studies suggest a benefit of adding local therapy, in the form of SAbR or surgery, to systemic therapy for NSCLC patients with limited metastases,” explained lead author Dr Puneeth Lyengar of the University of Texas Southwestern Medical Center, Dallas, Texas, US.

The study was terminated prematurely after an unplanned interim analysis at a median follow-up of 9.6 months, which found an overwhelming PFS benefit in SAbR-treated patients.

Median PFS was 9.7 months in the SAbR plus maintenance chemotherapy group vs 3.5 months in the maintenance chemotherapy alone group (hazard ratio, 0.304; p=0.01).

“Median PFS nearly tripled in patients who received SAbR prior to maintenance chemotherapy,” reported Lyengar. “We hope and expect that it will correlate with OS. However, median OS was not reached in both arms at the time of analysis. We were also unable to identify predictors of survival benefit owing to the small sample size of the study.”

The frequency of grade ≥3 adverse events was similar in both groups (n=4 with SAbR plus maintenance chemotherapy, n=3 with maintenance chemotherapy alone).

The choice of maintenance chemotherapy in the study was left to the discretion of the treating physicians, and consisted of pemetrexed (n=19), bevacizumab (n=4), gemcitabine (n=3), docetaxel (n=2) or erlotinib (n=1).

Ten patients receiving maintenance chemotherapy alone had disease progression, of which seven had progression at the primary tumour. Among patients who received SAbR plus chemotherapy, four experienced disease progression, but none of the sites of progression were within the radiated field.

“The clear and dramatic shift in patterns of progression suggests that SAbR effectively augments systemic therapy in controlling gross disease, which in turn shifts subsequent focus to prevention and control of distant sites,” suggested Lyengar. “This protection against local recurrence appears to have contributed to longer PFS, and may ultimately be shown to improve OS.”

“Two phase III studies have been initiated to further evaluate the OS benefit with SAbR in the treatment of NSCLC with limited metastases,” he added. [https://clinicaltrials.gov/ct2/show/NCT03137771; https://clinicaltrials.gov/ct2/show/NCT02417662]

“Despite the approval of immunotherapy in the first-line setting, there will still be a substantial proportion of patients with metastatic NSCLC who will receive chemotherapy as part of their treatment,” said Lyengar. “Therefore, the findings of this study will continue to be relevant to the management of NSCLC.”