Abstract

Simple SummaryThe 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.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.

Highlights

  • The management of advanced stage non-small cell lung cancer (NSCLC) has been revolutionized by the advent of targetable biomarkers

  • The progression is due to the onset of acquired resistance to the corresponding tyrosine kinase inhibitors (TKIs) with new genetic alterations arising in the epidermal growth factor receptor (EGFR) pathway or other cross-talk pathways, and for which new corresponding inhibitors are already available in early- and late-stage clinical trials [4]

  • In patients experiencing an oligoprogression after a durable response to EGFR-TKI, the strategy to maintain the inhibition of EGFR inhibitor-sensitive clones, to avoid the potential subsequent rebound tumor flare and symptomatic progression, is frequently used in clinical practice

Read more

Summary

Introduction

The management of advanced stage non-small cell lung cancer (NSCLC) has been revolutionized by the advent of targetable biomarkers. 20–30% of NSCLC patients with EGFR mutations who received EGFRTKIs were non-responsive or responded only for a short time due to intrinsic resistance to EGFR-TKIs. In most cases, the progression is due to the onset of acquired resistance to the corresponding TKIs with new genetic alterations arising in the EGFR pathway or other cross-talk pathways, and for which new corresponding inhibitors are already available in early- and late-stage clinical trials [4]. We review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI, with or without other agents, for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFRTKIs, discussing the controversies and potential future directions

Oligoprogressive Disease
Continuing EGFR-TKI Alone
78: No erlotinib
Continuing EGFR-TKI Plus Chemotherapy
Continuing EGFR-TKI Plus Other Targeted Agents
Central Nervous System Oligoprogression
Findings
Discussion
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call