Main clinical trials that explored predictive biomarkers in CRC
| Biomarker | Clinical trial | Results |
|---|---|---|
| RAS | PRIME [15] | The combination of panitumumab and FOLFOX4 significantly improved PFS in patients with KRAS wild-type tumors. |
| CRYSTAL [20] | Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy, thereby allowing the further tailoring of cetuximab administration to maximize patient benefit. | |
| OPUS [16] | The addition of cetuximab to FOLFOX-4 significantly improved PFS and response in patients with KRAS wild-type tumors. | |
| MRC COIN [17] | This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced CRC. | |
| FIRE-3 [23] | In this study a significantly higher OS was demonstrated for FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab in the extended RAS wild-type subgroup. | |
| NCT03600883 [35] | Early results suggest antitumor activity of single-agent AMG 510 in KRASG12C mutant solid tumors. | |
| NCT03785249 [33] | The trial is ongoing and responses to treatment with MRTX849 have been observed in both lung and CRC KRASG12C mutant patients. | |
| BRAF | SWOG 1406 [62] | The addition of vemurafenib to the combination of cetuximab and irinotecan in BRAFV600 mutated tumors resulted in a prolongation of PFS and a higher disease control rate. |
| BEACON CRC [63] | A combination of encorafenib, cetuximab, and binimetinib resulted in significantly longer OS and a higher response rate than standard therapy in patients with mCRC with the BRAF V600E mutation. | |
| MSI | NCT01876511 [71] | This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. |
| CheckMate 142 [73] | Nivolumab provided durable responses and disease control in pre-treated patients with dMMR/MSI-H mCRC. | |
| HER-2 | HERACLES [81] | The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive tumors. |
| MyPathway [86] | Durable responses were seen in patients with refractory colorectal cancers with HER2 activation/overexpression when the approved targeted therapy regimen administered without chemotherapy. | |
| CMSs | CALGB/SWOG 80405 [131] | The CMSs are highly prognostic and predictive for OS and PFS. |
| Fire-3(AIO KRK-0306) [132] | Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS2 and CMS4. |
OS: overall survival