1. BRAF + EGFR +/- MEK inhibitors after immune checkpoint inhibitors in BRAF V600E mutated and deficient mismatch repair or microsatellite instability high metastatic colorectal cancer.
- Author
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Ambrosini, Margherita, Tougeron, David, Modest, Dominik, Guimbaud, Rosine, Kopetz, Scott, Decraecker, Marie, Kim, Stefano, Coutzac, Clelia, Perkins, Geraldine, Alouani, Emily, Marmorino, Federica, Pernot, Simon, Sinicrope, Frank A, Elez, Elena, Parent, Pauline, Cremolini, Chiara, Pietrantonio, Filippo, Lonardi, Sara, Gallois, Claire, and Taieb, Julien
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PROTEINS , *MITOGEN-activated protein kinases , *COLORECTAL cancer , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *METASTASIS , *IMMUNE checkpoint inhibitors , *GLUTAMIC acid , *LONGITUDINAL method , *MUTAGENICITY testing , *ONCOGENES , *AMINO acids , *GENETIC mutation , *TUMORS , *LIVER , *COMPARATIVE studies , *PROGRESSION-free survival , *CONFIDENCE intervals , *EPIDERMAL growth factor receptors , *DISEASE progression - Abstract
Immune checkpoint inhibitors (ICIs) are the guideline endorsed first choice for patients with deficient mismatch repair or microsatellite instability high (dMMR/MSI-H) mCRC, however a significant proportion experience primary or secondary resistance. BRAF V600E mutated (BRAFm) and dMMR/MSI-H mCRC can be treated with BRAF + EGFR inhibitors but specific data on the efficacy after progression to ICIs are missing. We collected consecutive patients with BRAFm dMMR/MSI-H mCRC treated from 2017 to 2024 with a combination of BRAFi+EGFRi+/-MEKi, after disease progression on ICIs. A control cohort of BRAFm pMMR/MSS mCRC patients treated with encorafenib+cetuximab+/-binimetinib from 2nd line was used. dMMR/MSI-H (n = 50) BRAFm mCRC patients were more often > 70-year-old, with right-sided primary tumors, without liver but more lymphnode metastases than pMMR/MSS (n = 170). They were treated more frequently beyond 2nd line and 45 % were primary progressors to ICIs. Lower ORR (18 % versus 32 %, p = 0.09) and DCR (60 % versus 73 %, p = 0.11) was seen without reaching significance in dMMR/MSI-H as compared to pMMR/MSS patients. After a median follow-up of 14.04 months, no differences in PFS (median 5.13 versus 4.50 months, HR 0.83, 95 %CI: 0.57–1.20, p = 0.31) and OS (median 10.75 versus 9.11 months, HR 0.89, 95 %CI: 0.59–1.32, p = 0.55) were observed. Our results show that BRAFm dMMR/MSI-H mCRC patients benefit from BRAFi+EGFRi+/-MEKi after progression under ICIs. Despite lower ORR and DCR, the outcome is not different from that observed in pMMR/MSS BRAFm CRC and is in line with the results of the BEACON registration trial. • BRAFm dMMR/MSI-H mCRC benefit from BRAFi+EGFRi±MEKi at progression to ICIs. • Numerically lower ORR/DCR are observed for BRAFm dMMR/MSI-H vs pMMR/MSS mCRC. • PFS and OS to BRAFi+EGFRi±MEKi are similar in BRAFm dMMR/MSI-H and pMMR/MSS mCRC. • Higher severe toxicity rates to BRAFi+EGFRi±MEKi are seen for BRAFm dMMR/MSI-H mCRC. • Outcomes of BRAFm dMMR/MSI-H mCRC to BRAFi+EGFRi±MEKi are in line with BEACON trial. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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