Paradigm shift in local consolidative therapy for oligometastatic non-small cell lung cancer: a meta-analysis.
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ABSTRACT:
SUBMITTER: Cao C
PROVIDER: S-EPMC6976435 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Paradigm shift in local consolidative therapy for oligometastatic non-small cell lung cancer: a meta-analysis.
Cao Christopher C Chakos Adam A Guo Allen A Park John J JJ Saghaie Tajalli T Blinman Prunella P
Annals of translational medicine 20191201 Suppl 8
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Project description:In the last 20 years, significant strides have been made in our understanding of the biological mechanisms driving disease pathogenesis in metastatic non-small cell lung cancer (NSCLC). Notably, the development and application of predictive biomarkers as well as refined treatment regimens in the form of chemoimmunotherapy and novel targeted agents have led to substantial improvements in survival. Parallel to these remarkable advancements in modern systemic therapy has been a growing recognition of "oligometastatic disease" as a distinct clinical entity-defined by the presence of a controlled primary tumor and ≤5 sites of metastatic disease amenable to local consolidative therapy (LAT), with surgery or stereotactic ablative body radiotherapy (SABR). To date, three randomized studies have provided clinical evidence supporting the use of LAT/SABR in the treatment of oligometastatic NSCLC. In this review, we summarize clinical evidence from these landmark studies and highlight ongoing trials evaluating the use of LAT/SABR in a variety of clinical contexts along the oligometastatic disease spectrum. We discuss important implications and caveats of the available data, including considerations surrounding patient selection and application in routine clinical practice. We conclude by offering potential avenues for further investigation in the oligometastatic disease space.
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Project description:BackgroundLocal consolidative therapy (LCT) has emerged as a treatment option in patients with oligometastatic non-small cell lung cancer (NSCLC) undergoing chemotherapy or targeted therapy. However, the current literature lacks evidence as to whether LCT improves survival in NSCLC patients receiving immunotherapy. Our study aimed to assess whether LCT combined with pembrolizumab ± chemotherapy could improve the survival of patients with synchronous oligometastatic NSCLC.MethodsPatients with NSCLC, without EGFR or ALK genetic aberrations, who were treated with first-line pembrolizumab ± chemotherapy, were included in the study. Survival analysis of the LCT and non-LCT groups was compared.ResultsA total of 231 patients were included in the study. The median follow-up time was 15.24 months. Median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 12.00 and 23.43 months, respectively. Of the 231 patients included, 76 patients received LCT combined with pembrolizumab ± chemotherapy (LCT group) while 155 patients received pembrolizumab ± chemotherapy alone (non-LCT group). Of note, the PFS of the LCT and non-LCT groups was 13.97 and 10.08 months (p = 0.016), respectively. The OS were 30.67 and 21.97 months (p = 0.011), respectively. The PFS and OS were significantly improved with LCT for patients with brain or lung metastases but not bone metastases. No significant increase in treatment-related toxicity was observed in the LCT group.ConclusionsThe present study shows that LCT to metastatic sites is an option for consideration in patients with synchronous oligometastatic NSCLC during first-line pembrolizumab treatment, with significantly improved PFS and OS compared with systemic treatment alone.
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Project description:Standard treatments for patients with metastatic non-small cell lung cancer (NSCLC) include palliative chemotherapy and radiotherapy, but with limited survival rates. With the development of improved immunotherapy and targeted therapy, NSCLC prognoses have significantly improved. In recent years, the concept of oligometastatic disease has been developed, with randomized trial data showing survival benefits from local ablation therapy (LAT) in patients with oligometastatic NSCLC (OM-NSCLC). LAT includes surgery, stereotactic ablation body radiation therapy, or thermal ablation, and is becoming an important treatment component for OM-NSCLC. However, controversy remains on specific management strategies for the condition. In this review, we gathered current randomized trial data to analyze prognostic factors affecting patient survival, and explored ideal treatment conditions for patients with OM-NSCLC with respect to long-term survival.
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Project description:PurposeOur previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients with oligometastatic non-small-cell lung cancer (NSCLC) that did not progress after front-line systemic therapy. Herein, we present the longer-term overall survival (OS) results accompanied by additional secondary end points.Patients and methodsThis multicenter, randomized, phase II trial enrolled patients with stage IV NSCLC, three or fewer metastases, and no progression at 3 or more months after front-line systemic therapy. Patients were randomly assigned (1:1) to maintenance therapy or observation (MT/O) or to LCT to all active disease sites. The primary end point was PFS; secondary end points were OS, toxicity, and the appearance of new lesions. All analyses were two sided, and P values less than .10 were deemed significant.ResultsThe Data Safety and Monitoring Board recommended early trial closure after 49 patients were randomly assigned because of a significant PFS benefit in the LCT arm. With an updated median follow-up time of 38.8 months (range, 28.3 to 61.4 months), the PFS benefit was durable (median, 14.2 months [95% CI, 7.4 to 23.1 months] with LCT v 4.4 months [95% CI, 2.2 to 8.3 months] with MT/O; P = .022). We also found an OS benefit in the LCT arm (median, 41.2 months [95% CI, 18.9 months to not reached] with LCT v 17.0 months [95% CI, 10.1 to 39.8 months] with MT/O; P = .017). No additional grade 3 or greater toxicities were observed. Survival after progression was longer in the LCT group (37.6 months with LCT v 9.4 months with MT/O; P = .034). Of the 20 patients who experienced progression in the MT/O arm, nine received LCT to all lesions after progression, and the median OS was 17 months (95% CI, 7.8 months to not reached).ConclusionIn patients with oligometastatic NSCLC that did not progress after front-line systemic therapy, LCT prolonged PFS and OS relative to MT/O.
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Project description:BackgroundPrevious studies have shown the feasibility and effectiveness of local aggressive thoracic therapy (surgery and radiotherapy) for oligometastatic non-small cell lung cancer compared with systemic therapy, but with small sample. This study aims to perform a pooled analysis to explore whether LT could improve outcomes of oligometastatic patients with non-small cell lung cancer.MethodsProtocol of present study was registered on PROSPERO as number: CRD42021233095. PubMed, Embase and Web of knowledge were searched, and eligible studies investigating local therapy for non-small cell lung cancer with 1-5 metastases regardless of organs were included. Linear regression between survival and clinical characteristics were conducted. Hazard ratios of survival and adverse effects were merged. Pooled survival curves were carried out.ResultsThree randomized controlled trials and 5 cohort studies enrolling 499 patients were included. There was a trend that median overall survival declined with the increasing proportion of N2-3 positive patients in local therapy group, but with no statistical difference (P=0.09, R2=0.98). Undergoing local therapy for oligometastatic non-small cell lung cancer achieved reduction of 47% and 60% in the risk of death and cancer progression (P<0.001), respectively. In subgroup analysis, patients receiving local therapy including surgery showed hazard ratio of 0.33 on progression-free survival and 0.55 of these excluding surgery. Patients receiving consolidative local therapy (local therapy after systemic therapy) obtained hazard ratios 0.33 and 0.45 on progression-free and overall survival vs. systemic therapy, respectively. Hazard ratios of those receiving upfront local therapy (local therapy first) were 0.62 and 0.68 on progression-free and overall survival vs. systemic therapy. Pooled survival analysis showed median overall and progression-free survival of local therapy (21.6 and 14 months) group were both longer than systemic one (14.3 and 6.5 months). Odds ratio of adverse effects were no difference between 2 groups (P=0.16).ConclusionsLocal aggressive thoracic therapy could prolong 7 months overall and progression-free survival compared with systemic therapy in patients with oligometastatic non-small cell lung cancer. Consolidative local therapy might be a more favorable choice of local therapy. Benefits of local therapy for N2-3 positive patients should explored further.
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Project description:Oligometastatic cancer is characterized by a limited number of metastatic deposits. Compared with lung cancer patients who have more widespread disease, oligometastatic lung cancer patients have more favorable survival outcomes. Therefore, it has been hypothesized that local ablative therapy (LAT) directed at the metastatic deposits in addition to standard-of-care systemic therapy may further improve survival outcomes in oligometastatic lung cancer patients. One LAT modality that has been utilized in oligometastatic lung cancer is radiation therapy. In particular, ultra-hypofractionated radiotherapy, also known as stereotactic body radiotherapy (SBRT), has been shown to provide excellent local control with a favorable safety profile. Here, we reviewed the retrospective studies and prospective trials that have deployed radiation therapy as LAT in oligometastatic lung cancer, including randomized studies showing benefits for progression-free survival and overall survival with the addition of LAT. We also discuss the impact of targeted therapies and immunotherapy on radiation as LAT.
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