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

By A. Weickhardt, B. Scheier, J. Burke, G. Gan, Xian Lu, P. Bunn, D. Aisner, L. Gaspar, B. Kavanagh, R. Doebele and 1 more. Journal of Thoracic Oncology, 2012

642 citations recorded by the source corpus.

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.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/112962ecab0a82a5cb143b35fc7a83df66bb8341

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In Oncology

1. Jin-Yuan Shih
2. Shang-Gin Wu
3. Razelle Kurzrock
4. S. Patel

In Pulmonary and Respiratory Medicine

1. Jin-Yuan Shih
2. Shang-Gin Wu

Citations in the corpus

• PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy (2015, background): “Abrupt cessationof targeted therapy in this situationmay result in a dramatic tumor flare and current management of focal progression is to continue the TKI to treat the concerning lesion with local measures (67).”
• Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer (2018, positive): “This approach yielded more than six months of additional disease control [24, 25].”