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Local consolidative therapy improves survival in oligometastatic NSCLC
Aggressive consolidative therapy to the primary lesion and all metastatic sites appeared associated with improved OS among patients with synchronous oligometastatic non-small cell lung cancer, according to study results scheduled for presentation at Multidisciplinary Thoracic Cancers Symposium.
“Comprehensive local consolidation was associated with durable, long-term survival, with 1- and 5-year survival rates approximating that which was historically observed in earlier stages of disease,” Erin M. Corsini, MD, clinical research fellow at The University of Texas MD Anderson Cancer Center, said during a press cast. “Given our findings, we speculate that patients with adenocarcinoma, low intrathoracic disease burden and absence of bone metastases constitute those patients most likely to drive durable survival benefit.”
In the retrospective, single-institution study, Corsini and colleagues analyzed 194 patients (median age, 62 years; 111 men) with stage IV NSCLC and three or fewer synchronous metastatic lesions. Among these patients, 149 had adenocarcinoma and 136 had two to three distant metastasis (brain, n = 86; bone, n = 51; adrenal, n = 36; liver, n = 7).
A majority of patients (n = 175) received systemic therapy. Most also received local consolidative therapy to the primary lesion (n = 145), to all distant metastases (n = 147), and to all disease sites (n = 121).
Median follow up was 52.3 months (interquartile range [IQR], 29.9-98).
Researchers observed lower rates of locoregional progression among patients who received local consolidative therapy to the primary tumor compared with patients who did not (21% vs. 43%; P < .01).
Results showed median OS for all patients of 26.5 months (95% CI, 23-30).
Patients who underwent comprehensive local consolidative therapy achieved longer OS (29 months; range, 25-42) than patients who did not receive this therapy (23 months; range, 16-35). Further, comprehensive local consolidative therapy was associated with higher survival rates at 1 year (85% vs. 72%), 3 years (43% vs. 35%) and 5 years (32% vs. 19%).
Comprehensive local consolidative therapy appeared associated with improved OS when applied to all disease sites (HR = 0.67; 95% CI, 0.47-0.96), a trend that continued when applied to the primary lesion (HR = 0.71; 95% CI, 0.49-1.05). However, consolidative therapy to distant metastases did not appear associated with a survival benefit (HR = 0.77; 95% CI, 0.52-1.16)
Results of a multivariable analysis showed independent associations between improved OS and comprehensive local consolidative therapy to all sites of disease (HR = 0.68; 95% CI, 0.47-0.97) and adenocarcinoma histology (HR = 0.71; 95% CI, 0.56-0.9).
Univariable analysis showed an association between progression on first-line systemic therapy and increased risk for death (HR = 1.87; 95% CI, 1.15-3.02).
“We submit the observed rate of the systemic failure in this cohort highlights the need to further examine whether the benefits associated with this novel treatment paradigm can be further enhanced by the use of contemporary systemic agents,” Corsini said. – by John DeRosier
Reference:
Mitchell KG, et al. Abstract 1. Scheduled for presentation at: Multidisciplinary Thoracic Cancers Symposium; March 14-16, 2019; San Diego.
Disclosures: Corsini reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Multiple recent randomized trials suggest a PFS or OS advantage for the addition of local consolidative radiation in patients with oligometastatic NSCLC without progression after first-line systemic therapy. Similar results were noted in a broader cohort including patients with NSCLC, with the effect being potentially strong and measured in years (17 months with systemic therapy alone vs. 41.2 months with addition of consolidative radiation in the trial by Gomez and colleagues). The number of patients accrued was small (< 30 for Iyengar and colleagues, < 50 for Gomez and colleagues, and < 100 for Palma and colleagues), and the trials were conducted predominately in the absence of immune therapy, which also offers significant survival advantage above chemotherapy alone and now represents first-line therapy for metastatic NSCLC.
As such, it is not clear whether these early results can be generalized to a broader group of patients and incorporated into the standard of care. The larger multicenter, randomized trial NRG-LU002 remains open to more definitively establish the potential role of consolidative radiation after first-line systemic therapy.
The current abstract represents a larger retrospective series of the MD Anderson experience with oligometastatic NSCLC. It is valuable given both increased numbers (n = 194), and significantly longer available follow-up (52.3 months) than the available randomized trials.
In keeping with the results of the randomized trials, local consolidative radiation was associated with reduced locoregional progression and, when combined with treatment of metastatic sites, improved OS. This persisted on multivariable analysis and offers further support for the role of local consolidative radiation in oligometastatic NSCLC.
However, given significant potential heterogeneity within the metastatic NSCLC population, a retrospective study is unable to differentiate between correlation and causation, particularly when considering patients with lower burden of disease, lower-risk sites for treatment or better health may be more likely to receive local consolidative radiation. Such factors are difficult to correct for, even with multivariate analysis.
Although local consolidative radiation is generally well-tolerated in appropriately selected patients, and toxicity on the available randomized trials was in keeping with expectations, treatment-related deaths occurred in the SABR-COMET trial, and it is important to garner sufficient level-one evidence prior to altering a treatment paradigm for such a clinically significant patient population.
Data from NRG-LU002 will be crucial to confirming the role of consolidative stereotactic body radiation therapy in the management of oligometastatic NSCLC after first-line systemic therapy.
References:
Gomez DR, et al. Lancet Oncol. 2016;doi:10.1016/S1470-2045(16)30532-0.
Iyengar P, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2017.3501.
Palma DA, et al. Int J Radiat Oncol Biol Phys. 2018;doi:10.1016/j.ijrobp.2018.06.105.