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

SIMPLE SUMMARY: The oligoprogression concept is characterized by a limited number and/or sites of metastases in which a disease progression appears, and a more indolent tumor biology, raised specifically for oncogene addicted non-small cell lung cancer (NSCLC), including the epidermal growth factor receptor (EGFR)-mutant group. The optimal approach to the diagnosis and management of this disease state is not yet established. In fact, significant gaps still exist in our understanding of patient selection, type of progression, mechanisms responsible of intrinsic and acquired resistance, optimal systemic therapy, and the tumor microenvironment. Some therapeutic approaches are investigated and discussed in this review. Well-designed prospective clinical trials need to facilitate the development of therapeutic strategies beyond progression after first-line EGFR-inhibitor treatment failure. 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.