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Cited by 1,086Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study

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Gomez, Daniel R, Blumenschein, George R, Lee, J Jack, Hernandez, Mike, Ye, Rong, Camidge, D Ross, Doebele, Robert C, Skoulidis, Ferdinandos +16 more·2016·The Lancet Oncology
DOI 10.1016/s1470-2045(16)30532-0PMC PMC5143183
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Abstract

Background Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival.Methods In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four 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, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy ([chemo]radiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov, number NCT01725165.Findings Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52-20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7-20·9) versus 3·9 months (2·3-6·6) in the maintenance treatment group (hazard ratio 0·35 [90% CI 0·18-0·66], log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related).Interpretation Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario.Funding MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.

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Authors
Gomez, D. R., Blumenschein, G. R., Lee, J. J., Hernandez, M., Ye, R., Camidge, D. R., Doebele, R. C., Skoulidis, F., Gaspar, L. E., Gibbons, D. L., Karam, J. A., Kavanagh, B. D., Tang, C., Komaki, R., Louie, A. V., Palma, D. A., Tsao, A. S., Sepesi, B., William, W. N., Zhang, J., Shi, Q., Wang, X. S., Swisher, S. G., & Heymach, J. V.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • University of Colorado Anschutz (US)
  • London Health Sciences Centre (CA)
Corresponding author
Gomez, Daniel R
ORCID
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2016-12
Volume
17
Issue
12
Pages
1672-1682
ISSN
1470-2045 (ISSN-L)
DOI
10.1016/s1470-2045(16)30532-0
PMC
PMC5143183
OpenAlex
W2536769127
Cited by
1,086
References
31
Citations by year
2026: 61 · 2025: 79 · 2024: 93 · 2023: 116 · 2022: 135 · 2021: 129 · 2020: 138 · 2019: 160 · 2018: 109 · 2017: 58 · 2016: 5 · 2015: 1 · 2014: 1
FWCI
98.91
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc)
Funders
  • University of Texas MD Anderson Cancer Center
  • National Cancer Institute (P50CA058187, P30CA016672)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
oligometastatic non-small cell lung cancer, local consolidative therapy, maintenance therapy, observation, progression-free survival, chemoradiotherapy, metastasectomy, first-line systemic therapy, EGFR inhibitors, ALK inhibitors, platinum-based chemotherapy, early trial termination, metastasis-directed therapy, EGFR mutation, ALK rearrangement, central nervous system metastasis
MeSH terms
Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Metastasis

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