Atezolizumab for the treatment of colorectal cancer: <i>the latest evidence and clinical potential</i>

Rico, Gonzalo Tapia; Price, Timothy

doi:10.1080/14712598.2018.1444024

Cited by 29 publications

(21 citation statements)

References 42 publications

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“…Targeted therapies aimed at the RAS oncoproteins or the downstream signaling cascades have been ineffective and strategies specifically benefitting this subtype of CRC remain elusive. Recently there was excitement in this area with early investigations of the combination of cobimetinib, a MEK inhibitor, and atezolizumab, an anti-PD-L1 agent, showing promise in treatment refractory CRC [55]. Excitingly, in the phase I trial increased activity was seen specifically in those cancers with enhanced RAS/RAF/MEK/ERK signaling [36].…”

Section: Kras/nras Mutant Microsatellite Stablementioning

confidence: 99%

Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

DeStefanis

Kratz

Emmerich

et al. 2019

Curr Colorectal Cancer Rep

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Purpose of Review-Treatment options for patients with metastatic colorectal cancer continue to advance as the therapeutic implications of the molecular subtypes of this disease are becoming better understood. DNA sequencing and mismatch repair assessment are now standard of care analyses for patients with metastatic colorectal cancer Thi review describes important aspects of the biology of the clinically relevant molecular subtypes of colorectal cancer based on the current standard of care testing. In addition, the clinical treatment strategies available now and potentially in the future for these colorectal cancer subtypes are discussed. Recent Findings-Currently for metastatic colorectal cancer, standard of care molecular testing is done for mutations in exons 2, 3, and 4 of KRAS and NRAS, and BRAF V600E. Testing for mismatch repair (MMR) deficiency/microsatellite instability (MSI) status is also done. These aberrations are well known to change the clinical prognosis and guide patients' treatment strategies. Additionally, three new subtypes have emerged: PIK3CAmut, HER2 amplified, and NTRK fusions. With the addition of these emerging subtypes, tumor heterogeneity further validates the need to examine mCRC as a heterogeneous disease. Here we present recent exciting data from translational research and clinical trials exhibiting possible distinct treatment strategies for these different subtypes. Summary-Altogether these data show promising treatment strategies for many of these wellknown and emerging subtypes of mCRC. In addition, these also give better clinical prognostic and predictive information. We believe that as molecular testing expands PIK3CA mutation, HER2 amplification, and NTRK fusion molecular testing will be included in standard of care analyses.

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Section: Kras/nras Mutant Microsatellite Stablementioning

confidence: 99%

Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

DeStefanis

Kratz

Emmerich

et al. 2019

Curr Colorectal Cancer Rep

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“…The immunophenotype is also a key determinant that drives clinical decision in cancer and is now considered an additional challenge for immunotherapy. For example, Atezolizumab (anti-PD-L1) has shown encouraging activity against metastatic colorectal cancer when combined with chemotherapy and/or targeted therapies, especially with MEK inhibitor Cobimetinib [316]. Similarly, combination therapies of immunotherapy with existing chemotherapy, radiation or other immunotherapy with different mechanisms of action has been suggested to be evaluated to achieve excellent outcomes in patients with esophageal cancer [317].…”

Section: Mutational and Epigenetic Landscape In Tumor Progression mentioning

confidence: 99%

Current Perspectives in Cancer Immunotherapy

Christofi

Baritaki

Falzone

et al. 2019

Cancers

172

121

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Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.

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“…Several drugs and drug combinations are currently under investigation in an attempt to identify new, effective immunotherapy options against mCRC [47]. Table 3 summarizes selected clinical trials studying several ICIs and combinational therapies that have not received approval from regulatory authorities yet.…”

Section: Ongoing Clinical Trials With Icis In Mcrcmentioning

confidence: 99%

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis

Mavroudis

Sfakianaki

et al. 2020

Cancers

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Immunotherapy has considerably increased the number of anticancer agents in many tumor types including metastatic colorectal cancer (mCRC). Anti-PD-1 (programmed death 1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitors (ICI) have been shown to benefit the mCRC patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, ICI is not effective in mismatch repair proficient (pMMR) colorectal tumors, which constitute a large population of patients. Several clinical trials evaluating the efficacy of immunotherapy combined with chemotherapy, radiation therapy, or other agents are currently ongoing to extend the benefit of immunotherapy to pMMR mCRC cases. In dMMR patients, MSI testing through immunohistochemistry and/or polymerase chain reaction can be used to identify patients that will benefit from immunotherapy. Next-generation sequencing has the ability to detect MSI-H using a low amount of nucleic acids and its application in clinical practice is currently being explored. Preliminary data suggest that radiomics is capable of discriminating MSI from microsatellite stable mCRC and may play a role as an imaging biomarker in the future. Tumor mutational burden, neoantigen burden, tumor-infiltrating lymphocytes, immunoscore, and gastrointestinal microbiome are promising biomarkers that require further investigation and validation.

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Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential

Cited by 29 publications

References 42 publications

Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

Targeted Therapy in Metastatic Colorectal Cancer: Current Standards and Novel Agents in Review

Current Perspectives in Cancer Immunotherapy

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

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