General treatment for metastatic colorectal cancer: From KEYNOTE 177 study

Ding, Yuwei; Weng, Shanshan; Li, Xinyu; Zhang, Ding; Aisa, Adilai; Yuan, Ying

doi:10.1016/j.tranon.2021.101122

Cited by 4 publications

(2 citation statements)

References 9 publications

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“… 46 Increased CPI efficacy is seen in patients with MSI-H CRC tumors and as a result, pembrolizumab and nivolumab with or without ipilimumab are approved for treatment of these patients. 47 Unfortunately, 85% of patients with CRC have MSS tumors and successful treatment with immunotherapy is rare. 48 The size of TLSs that formed in these tumors was evaluated and scored as having high or low TLS activity, with higher TLS activity reflecting larger TLS formation on average as measured by an established histomorphometric method.…”

Section: Tertiary Lymphoid Structures In Gastrointestinal Malignancie...mentioning

confidence: 99%

The Role of Interleukin-7 in the Formation of Tertiary Lymphoid Structures and Their Prognostic Value in Gastrointestinal Cancers

Ware¹,

Wolfarth²,

Goon³

et al. 2022

Journal of Immunotherapy and Precision Oncology

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Immunotherapies for the treatment of solid tumors continue to develop in preclinical and clinical research settings. Unfortunately, for many patients the tumor fails to respond or becomes resistant to therapies such as checkpoint inhibitors (CPIs) targeting programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4). In many cancers, failed response to CPIs can be attributed to poor T cell infiltration, dominant immunosuppression, and exhausted immune responses. In gastrointestinal (GI) cancers T cell infiltration can be dismal, with several reports finding that CD8+ T cells compose less than 2% of all cells within the tumor. Organized aggregates of lymphocytes, antigen-presenting cells, and vessels, together termed tertiary lymphoid structures (TLSs), are hypothesized to be a major source of T cells within solid tumors. The intratumoral formation of these organized immune centers appears to rely on intricate cytokine and chemokine signaling to heterogeneous cell populations such as B and T cells, innate lymphoid cells, fibroblasts, and dendritic cells. In GI cancers, the presence and density of TLSs provide prognostic value for predicting outcome and survival. Further, TLS presence and density associates with favorable responses to CPIs in many cancers. This review highlights the prognostic value of TLSs in GI cancers, the role of the homeostatic cytokine interleukin-7 (IL-7) in TLS formation, and the induction of TLSs in solid tumors by novel therapeutics.

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Section: Tertiary Lymphoid Structures In Gastrointestinal Malignancie...mentioning

confidence: 99%

The Role of Interleukin-7 in the Formation of Tertiary Lymphoid Structures and Their Prognostic Value in Gastrointestinal Cancers

Ware¹,

Wolfarth²,

Goon³

et al. 2022

Journal of Immunotherapy and Precision Oncology

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“…To date, based on the result of phase III KEYNOTE-177 and phase II Checkmate-142 trial, the NCCN guideline recommends the use of pembrolizumab and nivolumab ± ipilimumbab in the first-line and non-first-line settings in MSI-H/dMMR mCRC patients. Moreover, the checkpoint inhibitors regimens are also recommended in the neoadjuvant setting for resectable mCRC with MSH-I/dMMR status [30,31].…”

Section: Introductionmentioning

confidence: 99%

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade

Gorzo

Galos

Lungulescu

et al. 2022

Life

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Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/− ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use.

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SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAF V600E-mutant mCRC

Elez,

Kopetz,

Tabernero

et al. 2023

Future Oncol.

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Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination of pembrolizumab with encorafenib and cetuximab versus pembrolizumab alone in patients with previously untreated BRAF V600E-mutant, MSI-H/dMMR mCRC.

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General treatment for metastatic colorectal cancer: From KEYNOTE 177 study

Cited by 4 publications

References 9 publications

The Role of Interleukin-7 in the Formation of Tertiary Lymphoid Structures and Their Prognostic Value in Gastrointestinal Cancers

The Role of Interleukin-7 in the Formation of Tertiary Lymphoid Structures and Their Prognostic Value in Gastrointestinal Cancers

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade

SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAF V600E-mutant mCRC

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