Rapid progression of disease from immunotherapy following targeted therapy: insights into treatment management and sequence

With emerging promising therapeutic regimens in non-small cell lung cancer (NSCLC), the standard-of-care treatments for a variety of histologic and mutated subgroups in NSCLC has been regularly shifting in response to landmark clinical trials. However, with the availability of a range of therapeutic agents, clear grouping of patient populations to appropriate treatment strategies is essential. In this review, we illustrate past and current treatment strategies in NSCLC, specifically focusing on targeted therapy and immunotherapy. We describe a complex clinical scenario that oncologists will encounter of patients with multiple actionable mutations such as epidermal growth factor receptor (EGFR) sensitizing mutations and high expression of programmed death-ligand 1 (PD-L1). Recent data regarding sequential therapy of EGFR tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) demonstrate severe adverse interactions between the therapies that impact patient quality-of-life and outcomes. As we enter further into an era of personalized and precision medicine, guidelines and standard-of-care therapies are essential to define separate patient groups based on molecular testing, histology, comorbidities, and more. This article explores the current status of generally understudied patient groups in NSCLC and proposes future directions in therapeutic strategies.