Local Consolidative Therapy vs Observation in Limited Metastatic NSCLC

Local consolidative therapy (LCT) boosted overall survival (OS) compared with maintenance therapy/observation (MT/O) in patients with oligometastatic (ie, limited) non–small-cell lung cancer (NSCLC), according to research presented at the 2018 American Society for Radiation Oncology (ASTRO) Annual Meeting.

“We previously observed that LCT improves progression-free survival (PFS) in patients with oligometastatic NSCLC after front-line systemic therapy without progression. Here we report the final analysis of this trial, including the mature secondary endpoint of OS,” wrote the study authors, led by Daniel R. Gomez, MD, who is associate medical director, service chief of the Thoracic Section, and associate professor in the Department of Radiation Oncology, Division of Radiation Oncology, at The University of Texas MD Anderson Cancer Center in Houston.

In a multicenter, randomized, controlled phase II trial, researchers evaluated 49 patients with stage IV NSCLC with 3 or fewer metastatic lesions. Additional inclusion criteria were an ECOG performance status of 2 or lower and no progression following front-line systemic therapy. Standard front-line systemic therapy consisted of either 4 or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements.

Dr. Gomez and colleagues randomized patients to receive either standard MT/O or LCT. LCT consisted of radiation or surgery to all remaining active sites of disease followed by MT/O. The primary endpoint was PFS. Secondary endpoints included OS, toxicity, and time to appearance of a new lesion.

The investigators previously reported the results of this trial with a median follow-up of 12.4 months, which showed a benefit in PFS. In the current study, the median follow-up was 38.8 months.

A durable PFS benefit, with a median of 14.2 months, was observed in the LCT group (95% CI, 7.4–24.3) vs 4.4 months in the MT/O arm (95% CI, 2.2–8.3; P = .014). This benefit was also observed in LCT patients during extended follow-up. No new grade 3 or higher toxicities were reported.

“To our knowledge, this study represents the first randomized data showing an OS benefit for local ablative therapy in patients with oligometastatic NSCLC that do not progress after front-line systemic therapy,” concluded the researchers. “Ongoing phase II/III trials will assess the effect of LCT in larger populations and with the incorporation of novel therapeutic agents (immunotherapy, targeted therapy).”

In an interview with Cancer Network, Benjamin Kann, MD, who is a radiation oncologist at Yale Cancer Center in New Haven, Connecticut, commented on the significance of the Gomez et al study and how it compares with other studies.

“This is the first prospective, randomized study to demonstrate that local tumor therapy improves overall survival in patients with limited metastatic-or oligometastatic-non–small-cell lung cancer. Median overall survival was 2 years greater in patients who received local therapy upfront. The study suggests that local therapy should be considered for patients with limited metastatic disease (3 lesions or fewer), whose disease has not progressed following chemotherapy and can be safely treated with radiotherapy and/or surgery,” he said. “Prior studies have shown similar substantial improvements in progression-free survival for this population, though they had not been powered to detect an overall survival benefit. Of note, the results of this study are comparable to those from the simultaneously presented SABR-COMET trial, which hints at improved overall for patients with limited metastatic disease from several primary cancer types (not just lung cancer) who receive local radiotherapy to their lesions.”

Dr. Kann also commented on the future significance of the results. “The study suggests that local therapy should be considered for patients with limited metastatic non–small-cell lung cancer who have not progressed following systemic therapy, and whose disease sites are amenable to radiotherapy and/or surgery. This study should encourage further investigation to determine the effect of local therapy in larger patient sample sizes and in the context of immunotherapy.”