Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer

Weickhardt, Andrew J.; Scheier, Benjamin; Burke, Joseph Malachy; Gan, Gregory; Lu, Xian; Bunn, Paul A.; Aisner, Dara L.; Gaspar, Laurie E.; Kavanagh, Brian D.; Doebele, Robert C.; Camidge, D. Ross

doi:10.1097/jto.0b013e3182745948

Cited by 684Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentBrain Metastases and Treatment

Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer

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Weickhardt, Andrew J., Scheier, Benjamin, Burke, Joseph Malachy, Gan, Gregory, Lu, Xian, Bunn, Paul A., Aisner, Dara L., Gaspar, Laurie E. +3 more·2012·Journal of Thoracic Oncology

DOI 10.1097/jto.0b013e3182745948PMC PMC3506112

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Abstract

Introduction Many patients with oncogene-driven non-small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors experience limited sites of disease progression. This study investigated retrospectively the benefits of local ablative therapy (LAT) to central nervous system (CNS) and/or limited systemic disease progression and continuation of crizotinib or erlotinib in patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT) NSCLC, respectively.Methods Patients with metastatic ALK+ NSCLC treated with crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were identified at a single institution. Initial response to the respective kinase inhibitors, median progression-free survival (PFS1), and site of first progression were recorded. A subset of patients with either nonleptomeningeal CNS and/or four sites or fewer of extra-CNS progression (oligoprogressive disease) suitable for LAT received either radiation or surgery to these sites and continued on the same tyrosine kinase inhibitors. The subsequent median progression-free survival from the time of first progression (PFS2) and pattern of progression were recorded.Results Median progression-free survival in ALK+ patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery) and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients progressed again, with median PFS2 of 6.2 months.Discussion Oncogene-addicted NSCLC with CNS and/or limited systemic disease progression (oligoprogressive disease) on relevant targeted therapies is often suitable for LAT and continuation of the targeted agent, and is associated with more than 6 months of additional disease control.

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In that series, median duration of targeted therapy beyond progression was 6.2 months (7.1 months in CNS-only progression and 4.0 months in extracranial progression).
“median duration of targeted therapy beyond progression of 6.2 months (7.1 months in CNS-only progression and 4.0 in extracranial progression).”
From The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer: Status in 2016 (2016) · cites this paper as [125]
In a series of 25 patients with oncogene-driven NSCLC (15 ALK-driven and 10 EGFR-driven) treated with local ablative therapy, median time to first oligoprogressive disease was 9.8 months.
“In a series cohort of 25 patients with oncogene-driven NSCLC (15 anaplastic lymphoma receptor tyrosine kinase gene [ALK] driven and 10 EGFR driven) treated with local ablative therapy, the median time to first oligoprogressive disease was 9.8 months”
From The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer: Status in 2016 (2016) · cites this paper as [125]
Retrospective series and case reports suggest that continuing an EGFR TKI with local treatment may be reasonable in patients with single-site radiological progression, ongoing driver oncogene addiction, and no rapid systemic progression.
“Evidence from retrospective series and case reports suggests that, in patients where there is evidence of radiological progression in a single site (i.e.CNS metastasis or adrenal gland), but with ongoing dependence on the driver oncogene addiction and without rapid systemic progression, the combination of continuing the EGFR TKI with local treatment (radiotherapy or surgery) may represent a reason”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [132]

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“6 months after LAT of isolated CNS progression in 17 NSCLC patients who had achieved at least stable disease for more than 6 months on an EGFR-TKI,(21) and an American group reported a median PFS2 of 10 months in 18 NSCLC patients with EGFR-MT after LAT of isolated sites of eCNS progression.(49) In our series, no pati…”
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[53]Costa DB Kobayashi S Pandya SS CSF Concentration of the Anaplastic Lymphoma Kinase Inhibitor Crizotinib Journal of Clinical Oncology 2011 29 e443 e445 21422405

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Authors: Weickhardt, A. J., Scheier, B., Burke, J. M., Gan, G., Lu, X., Bunn, P. A., Aisner, D. L., Gaspar, L. E., Kavanagh, B. D., Doebele, R. C., & Camidge, D. R.
Affiliations: University of Colorado Cancer Center (US)
Colorado School of Public Health (US)
ORCID: Weickhardt, Andrew J.
Burke, Joseph Malachy
Gan, Gregory
Lu, Xian
Bunn, Paul A.
Aisner, Dara L.
Kavanagh, Brian D.
Doebele, Robert C.
Camidge, D. Ross
Venue: Journal of Thoracic Oncology
Publisher: Elsevier BV
Published: 2012-12
Volume: 7
Issue: 12
Pages: 1807-1814
ISSN: 1556-0864 (ISSN-L)
DOI: 10.1097/jto.0b013e3182745948
PMC: PMC3506112
OpenAlex: W2030227571
Cited by: 684
References: 62
Citations by year: 2026: 22 · 2025: 30 · 2024: 39 · 2023: 42 · 2022: 39 · 2021: 54 · 2020: 43 · 2019: 51 · 2018: 65 · 2017: 72 · 2016: 77 · 2015: 77 · 2014: 51 · 2013: 21
FWCI: 38.44
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1096 d)
Locations: Journal of Thoracic Oncology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P50CA058187, P30CA046934)
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 › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
Keywords: local ablative therapy, oligoprogressive disease, non-small cell lung cancer, tyrosine kinase inhibitors, crizotinib, erlotinib, ALK rearrangement, EGFR mutation, central nervous system metastasis, radiotherapy, progression-free survival
MeSH terms: Erlotinib Hydrochloride, Crizotinib, Anaplastic Lymphoma Kinase, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Prognosis, Pyrazoles, Pyridines, Quinazolines, Retrospective Studies, Gene Rearrangement, Survival Rate, Catheter Ablation, Disease Progression, Receptor Protein-Tyrosine Kinases, Protein Kinase Inhibitors, Young Adult, ErbB Receptors

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Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer

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