Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study

Original: J Clin Oncol; 37: 1558-65

Author(s): Gomez DR, Tang C, Zhang J, et al

Reviewer: Vasileios S. Skouras MD

Published: 08 Aug, 2019

The study is a multicenter, phase II, randomized trial that included patients with oligometastatic stage IV non-small-cell lung cancer (NSCLC) and no disease progression after the standard first-line systemic therapy. Oligometastatic status was defined by the presence of up to three metastases (not including the primary tumor) while standard first-line systemic therapy included at least four cycles of platinum-based chemotherapy, or at least 3 months of targeted therapy with an EGFR-TKI or ALK-inhibitor for tumors with actionable EGFR mutations or ALK re-arrangement, respectively. The patients were randomized to either local consolidative therapy (LCT) with radiation therapy or surgery followed by maintenance or observation (LCT arm) or to standard maintenance or observation (MT/O arm). The primary outcome was progression-free survival (PFS) with secondary outcomes being overall survival (OS), toxicity and appearance of new lesions. A total of 49 (n=25 in the LCT and n=24 in the MT/O arm) patients had been randomized before the early closure of the trial due to a significant PFS benefit in the LCT arm. After a median follow-up time of 38.8 months, a statistically significant benefit in PFS (14.2 vs. 4.4 months), OS (41.2 vs. 18.9 months) and time to appearance of new lesions (14.2 vs. 6.0 months) was confirmed for the patients in the LCT arm, who also experienced no additional severe (grade 3 or greater) toxicities compared to the MT/O arm. The authors concluded that LCT improves PFS and OS of patients with oligometastatic disease that does not progress after standard first-line systemic treatment.

In contrast to the curative-intent treatment strategies (i.e. surgical resection, radiotherapy, chemoradiation) that are currently used in stage I-III NSCLC, the management of NSCLC patients with distant metastases (i.e. stage IV disease) has been classically based on the administration of only systemic therapy, which however is associated with a negligible (i.e. <5%) probability of curing the disease. LCT with the use of newer radiotherapy techniques in the context of chemoradiation with or without subsequent surgical resection has been shown to be beneficial in patients with locally advanced disease (i.e. those with metastases to mediastinal lymph nodes). The question then arose whether we could move one step forward to use a similar approach in patients with limited number of distant metastases (i.e. oligometastatic disease), with a widely accepted definition (as to the number of metastases) of oligometastatic disease lacking though. Despite the limitations (low number of included patients and heterogeneity in first-line treatment regimens), the promising results of this study seem to signal the beginning of a new era in the management of metastatic NSCLC. Further studies are definitely required not only to confirm the results in larger populations but also to accurately define oligometastatic disease before the routine use of such strategies in clinical practice.

Respiratory digests
Thoracic oncology