Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies

Abstract

A proportion of patients with lung cancer experience long-term clinical benefit with immune checkpoint inhibitors (ICIs). However, most patients develop disease progression during treatment or after treatment discontinuation. Definitions of immune resistance are heterogeneous according to different clinical and biologic features. Primary resistance and acquired resistance, related to tumor-intrinsic and tumor-extrinsic mechanisms, are identified according to previous response patterns and timing of occurrence. The clinical resistance patterns determine differential clinical approaches. To date, several combination therapies are under development to delay or prevent the occurrence of resistance to ICIs, including the blockade of immune coinhibitory signals, the activation of those with costimulatory functions, the modulation of the tumor microenvironment, and the targeting T-cell priming. Tailoring the specific treatments with distinctive biologic resistance mechanisms would be ideal to improve the design and results of clinical trial. In this review, we reviewed the available evidence on immune resistance mechanisms, clinical definitions, and management of resistance to ICIs in lung cancer. We also reviewed data on novel strategies under investigation in this setting.

A Nomogram to Predict Survival in Patients With Locoregional Recurrent Nasopharyngeal Carcinoma Receiving Comprehensive Treatment

“…Currently, therapeutic decisions making and prognostic stratification for NPC are based on TNM stage system, and patients are stratified according to the anatomical region. Instead of full consideration of the biological heterogeneity of cancer ( 15 ), this is often insufficient for prognostic stratification and individualized treatment. In addition, the stage system of recurrence uses the TNM stage, which is the same system for initial diagnosed NPC, and this would decrease the accuracy of the prognostic stratification ( 16 , 17 ).For recurrent patients, accurate prognostic stratification and individualized treatment are very important ( 18 , 19 ).…”

Immunotherapy, radiation oncology and radiology: An alliance into the future

“…Amidst the promise of immunotherapy is the sobering observation that a vast majority of cancers will either not respond to immune checkpoint inhibitors upfront or will develop treatment resistance at a later stage 2 . From a radiation oncology standpoint, there is an increasing body of pre‐clinical and clinical evidence for the synergistic efficacy and safety of combining radiation therapy with immunotherapy to overcome points of treatment failure.…”

“…Amidst the promise of immunotherapy is the sobering observation that a vast majority of cancers will either not respond to immune checkpoint inhibitors upfront or will develop treatment resistance at a later stage. 2 From a radiation oncology standpoint, there is an increasing body of pre-clinical and clinical evidence for the synergistic efficacy and safety of combining radiation therapy with immunotherapy to overcome points of treatment failure. Here, it is our opinion that radiation oncologists cannot afford to be passive in engaging with the opportunities presented by the confluence of immunotherapy and radiation therapy, especially in light of the paradigm shifts that the immuno-oncology revolution has ushered in.…”

Comparison of real-world data (RWD) analysis on efficacy and post-progression outcomes with pembrolizumab plus chemo vs chemo alone in metastatic non-squamous non-small cell lung cancer with PD-L1 < 50%

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