Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations

Abstract

After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

“…Oligometastatic status was defined as a maximum of 5 metastases in 3 organs, but diffuse plasma membrane (meningeal, pleural, pericardial, and mesenteric) or bone marrow metastases were not included in this definition [18] . Oligoprogressive disease is a special condition, which is defined as disease progression at a limited number of anatomical sites (not more than 5 sites of progression and 2 organs), whereas there is continued response or stable disease at other sites, the biology of tumours is more inclined to be indolent [19] .…”

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

“…Oligoprogression is a relatively new concept which has emerged as effective local therapies became available, referring to progressive lesions restricted in both number and involved sites, typically less than five. 63 , 64 …”

“…Oligoprogression is a relatively new concept which has emerged as effective local therapies became available, referring to progressive lesions restricted in both number and involved sites, typically less than five. 63,64 Several real-world datasets have explored the patterns of disease progression after osimertinib. One report has suggested that EGFR T790Mpositive NSCLC patients treated with osimertinib are more likely to progress with oligoprogressive lesions (72%) than overt systemic progressive lesions (28%).…”

Oligoprogression in non-small cell lung cancer: a narrative review

“…Oligoprogressive lesions following SBRT for organ confined disease often first appear in the organ confined site before progressing to distant extra organ sites ( 17 ). In the situation of EGFR + NSCLC patients on tyrosine kinase inhibitor (TKI) therapy, most studies have indicated that the lung as the most common area of progression, with the CNS, and thoracic lymph nodes being the most common other site of progression ( 18 ). Other studies however have indicated the CNS as the most common site of oligoprogression for EGFR + NSCLC ( 19 ).…”