Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials
In metastatic colorectal cancer (mCRC), remarkable advances have been achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, only in a small subset of tumours (4–5%), harbouring a deficient mismatch repair system (dMMR)/microsatellite instability–high (MSI-H) or mutations...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/1/52 |
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| author | Marco Maria Germani Roberto Moretto |
| author_facet | Marco Maria Germani Roberto Moretto |
| author_sort | Marco Maria Germani |
| collection | DOAJ |
| description | In metastatic colorectal cancer (mCRC), remarkable advances have been achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, only in a small subset of tumours (4–5%), harbouring a deficient mismatch repair system (dMMR)/microsatellite instability–high (MSI-H) or mutations in the catalytic subunit of polymerase epsilon (<i>POLE</i>). Within this framework, several combination strategies have been investigated to sensitize proficient mismatch repair (pMMR)/microsatellite stable (MSS) mCRC to ICIs, with disappointing results so far. However, at the last ESMO meeting, two phase II trials AtezoTRIBE and MAYA provided promising results in this field. In the comparative AtezoTRIBE trial, the addition of atezolizumab to FOLFOXIRI (5-fluoruracil, oxaliplatin and irinotecan) and bevacizumab led to a significant advantage in terms of progression free survival (PFS) in a population of untreated mCRC patients, not selected according to MMR/MSI status. In the single-arm MAYA trial, immune priming with temozolomide in pMMR/MSS chemo-resistant mCRC patients with silencing of O6-methylguanine-DNA methyltransferase (<i>MGMT</i>) allowed reporting signals of sensitivity to the subsequent therapy with nivolumab and a low dose of ipilimumab in some patients. Here, we discuss the rationale, results, criticisms and research perspectives opened by these two studies. |
| first_indexed | 2024-03-10T03:47:29Z |
| format | Article |
| id | doaj.art-9cf779dc78fe47f290225d8dbea0a1a5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T03:47:29Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9cf779dc78fe47f290225d8dbea0a1a52023-11-23T11:15:16ZengMDPI AGCancers2072-66942021-12-011415210.3390/cancers14010052Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA TrialsMarco Maria Germani0Roberto Moretto1Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma, 67, 56126 Pisa, ItalyUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Via Roma, 67, 56126 Pisa, ItalyIn metastatic colorectal cancer (mCRC), remarkable advances have been achieved with immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, only in a small subset of tumours (4–5%), harbouring a deficient mismatch repair system (dMMR)/microsatellite instability–high (MSI-H) or mutations in the catalytic subunit of polymerase epsilon (<i>POLE</i>). Within this framework, several combination strategies have been investigated to sensitize proficient mismatch repair (pMMR)/microsatellite stable (MSS) mCRC to ICIs, with disappointing results so far. However, at the last ESMO meeting, two phase II trials AtezoTRIBE and MAYA provided promising results in this field. In the comparative AtezoTRIBE trial, the addition of atezolizumab to FOLFOXIRI (5-fluoruracil, oxaliplatin and irinotecan) and bevacizumab led to a significant advantage in terms of progression free survival (PFS) in a population of untreated mCRC patients, not selected according to MMR/MSI status. In the single-arm MAYA trial, immune priming with temozolomide in pMMR/MSS chemo-resistant mCRC patients with silencing of O6-methylguanine-DNA methyltransferase (<i>MGMT</i>) allowed reporting signals of sensitivity to the subsequent therapy with nivolumab and a low dose of ipilimumab in some patients. Here, we discuss the rationale, results, criticisms and research perspectives opened by these two studies.https://www.mdpi.com/2072-6694/14/1/52metastatic colorectal cancerproficient mismatch repair system/microsatellite stabilityimmune checkpoint inhibitorsFOLFOXIRI/bevacizumabtemozolomide |
| spellingShingle | Marco Maria Germani Roberto Moretto Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials Cancers metastatic colorectal cancer proficient mismatch repair system/microsatellite stability immune checkpoint inhibitors FOLFOXIRI/bevacizumab temozolomide |
| title | Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials |
| title_full | Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials |
| title_fullStr | Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials |
| title_full_unstemmed | Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials |
| title_short | Immune Checkpoint Inhibitors in Mismatch Repair Proficient/Microsatellite Stable Metastatic Colorectal Cancer Patients: Insights from the AtezoTRIBE and MAYA Trials |
| title_sort | immune checkpoint inhibitors in mismatch repair proficient microsatellite stable metastatic colorectal cancer patients insights from the atezotribe and maya trials |
| topic | metastatic colorectal cancer proficient mismatch repair system/microsatellite stability immune checkpoint inhibitors FOLFOXIRI/bevacizumab temozolomide |
| url | https://www.mdpi.com/2072-6694/14/1/52 |
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