Stereotactic ablative radiotherapy for acquired resistance to EGFR therapy in metastatic non-small cell lung cancer

Abstract

The advent of targeted therapy has transformed the treatment paradigm and survival of patients with metastatic non-small cell lung cancer (NSCLC) with driver mutations. The development of acquired resistances during treatment with tyrosine kinase inhibitors (TKIs) impedes a prolonged survival in many patients. This fact is leading to the use of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) to counter these resistances. SABR is a non-invasive treatment that can be delivered in multiple locations and has already proven effective in oligometastatic disease. Clinical evidence suggests that the combination of SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with mutations in epidermal growth factor receptor (EGFR), with international guidelines recommending their use in unfavorable scenarios such as oligoprogressive disease. In this publication, we have reviewed the available evidence on EGFR-TKIs resistance mechanisms and the combination of SABR with TKI in metastatic NSCLC with EGFR mutations. We also describe the utility and clinical recommendations of this combination in oligometastatic and oligoprogressive disease.

Bombarding Oligoprogression

“…However, when encountering extracranial oligoprogression, treating physicians often face the dilemma of discontinuing the current systemic therapy despite a favorable response in all other sites and switching to a next-line systemic therapy. This type of clinical scenario has led to the investigation of locally ablative therapy (LAT), such as stereotactic body RT (SBRT), which can provide durable local control even in the metastatic setting for use against oligoprogression 7–9 . The intent of LAT in oligoprogression, the basis of our current study, is to delay the time to next-line therapy by providing a progression-free interval benefit.…”

“…This type of clinical scenario has led to the investigation of locally ablative therapy (LAT), such as stereotactic body RT (SBRT), which can provide durable local control even in the metastatic setting for use against oligoprogression. [7][8][9] The intent of LAT in oligoprogression, the basis of our current study, is to delay the time to nextline therapy by providing a progression-free interval benefit. Institutional data with small cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase-mutated lung cancers treated with LAT have demonstrated favorable PFS intervals ranging from 4 to 10 months.…”

“…The intent of LAT in oligoprogression, the basis of our current study, is to delay the time to next-line therapy by providing a progression-free interval benefit. Institutional data with small cohorts of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase-mutated lung cancers treated with LAT have demonstrated favorable PFS intervals ranging from 4 to 10 months 7–9 . The primary purpose of our study is to assess patients with metastatic NSCLC who have received systemic therapy and have had extracranial oligoprogression treated with ablative RT and to assess their oncologic outcomes and toxicity.…”

Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review

“…However, unpredictable drug resistance limits its clinical efficacy (6). For patients with drug resistance, in addition to using new generation inhibitors or combination therapy, radiotherapy may also overcome or delay targeted drug resistance (7)(8)(9)(10). Radiotherapy, as a palliative treatment for patients with late stage recurrent and metastatic tumors, has a wide range of applications, accurate ejaculation, and relatively small side effects.…”