Paradigms on Immunotherapy Combinations with Chemotherapy

Abstract

Checkpoint inhibitors are being added to standard-of-care chemotherapy in multiple clinical trials. Success has been reported in non–small and small cell lung carcinomas and urothelial, head and neck, gastric, and esophageal cancers, and promising results are already available in triple-negative breast and pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor cell death, antiangiogenesis, selective depletion of myeloid immunosuppressive cells, and lymphopenia, which reduces regulatory T cells and makes room for proliferation of effector T cells. However, chemotherapy regimens have not been optimized for such combinations, perhaps explaining some recent clinical trial disappointments. Approaches to make the most of chemoimmunotherapy include neoadjuvant and adjuvant schemes. Significance: Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management. Evidence in phase III clinical trials already supports combinations of immunotherapy with standard-of-care chemotherapy for a number of malignant diseases. This review focuses on such evidence and provides an overview of the potential synergistic mechanisms of action and the opportunities to optimize chemoimmunotherapy regimens.

NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

“…Currently, surgical resection remains the most effective treatment for early GC. Chemotherapy, radiotherapy, and other new therapies, such as immunotherapy and molecular targeted therapy, also play a significant role in the prognosis [ 3 ]. However, the prognosis of metastatic, recurrent, and advanced GC is still not satisfactory, and the mechanism of GC progression and metastasis formation is poorly understood.…”

Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors

“…Our study population also included patients receiving combinations of ICIs with molecularly targeted therapies or cytotoxic chemotherapies, commonly used as standard-of-care regimens in solid tumor cancers. 22 , 23 , 24 The inclusiveness of our eligibility criteria is intended to facilitate the generalizability of our findings toward diverse ICI-based combination regimens, which compose the majority of immunotherapies currently used or under investigation in solid tumor cancers. The distribution of adverse events observed in our study (eFigure 7 in the Supplement ) reflected known rates of adverse events with ICI regimens in genitourinary cancers, with the exception of hyperglycemia, which was more frequently observed in this cohort.…”

An Indirect Comparison Between Nivolumab + Ipilimumab + Two Cycles of Chemotherapy vs. Pembrolizumab + Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer

“…Considerable OS benefit of this chemo-light combination therapy is attributed to several aspects. First, short cycle chemotherapy can increase tumor immunogenicity by eliminating tumor cells and releasing antigen ( 10 , 22 ), and is also associated with enhanced PD-L1 expression and potentiated T cell-mediated cytotoxicity while treated with nivolumab ( 23 ). Moreover, distinct immune checkpoint inhibitors function in complementary mechanisms with improved efficacy ( 24 , 25 ).…”