Authors: Sara Baglivo, Martina Mandarano, Guido Bellezza, Vincenzo Minotti, Angelo Bonaiti, Matthias J. Fischer, Ilaria Birocchi, Fausto Roila, Niccolò Metelli, Vienna Ludovini & Giulio Metro
Abstract
Treatment with immune checkpoint inhibitors (ICIs) that target the programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) axis is usually ineffective in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), either as first-line treatment or in later lines. By contrast, especially for patients with common EGFR mutations (exon 19 deletion/L858R point mutation), an orally bioavailable EGFR tyrosine kinase inhibitor (EGFR-TKI) is the best upfront therapy, being able to provide response rates well above 50% and a median progression-free survival ranging from 11 to 19 months, depending on whether a second-generation (e.g., afatinib) or a third-generation (i.e., osimertinib) EGFR-TKI is used. Unfortunately, treatment options for these patients at the time of acquired resistance are limited. As for afatinib-pretreated patients, those who develop a T790M mutation may benefit from osimertinib, whereas platinum-based chemotherapy is the preferable therapeutic strategy for T790M-negative patients as well as for patients who progress on osimertinib administered as first-line therapy. Here, we describe the case of an exon-19-deleted patient who experienced a complete response to the anti-PD-1 agent pembrolizumab upon the development of T790M-negative acquired resistance to afatinib. Furthermore, we discuss this case in the context of the existing literature, especially focusing on the importance of evaluating multiple markers of immune response post-EGFR-TKI and prior to ICI treatment in order to select the best treatment strategy in this clinical scenario.
Key Summary Points |
Treatment with immune checkpoint inhibitors is generally poorly effective for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients who experience acquired resistance to an EGFR-tyrosine kinase inhibitor (TKI). |
Here, we present the case of an EGFR-mutated NSCLC patient who underwent a complete response to the anti-programmed cell death 1 (PD-1) agent pembrolizumab upon disease progression on the EGFR-TKI afatinib. |
Emphasis is placed on the serial measurement of multiple immune markers in tumor tissue as potential predictors of response to immunotherapy. |
In our case, programmed cell death ligand-1 (PD-L1) expression, tumor mutation burden, as well as the presence/absence of CD8+ and FOXP3+ Tregs tumor-infiltrating lymphocytes were useful markers for the existence of an inflamed phenotype. |
Evaluating the aforementioned markers can help guide treatment decisions on whether EGFR-mutated NSCLCs with acquired resistance to an EGFR-TKI could benefit from immunotherapy. |