The Current Molecular Treatment Landscape of Advanced Colorectal Cancer and Need for the COLOMATE Platform

[...]utilizing NGS data from a tumor biopsy of 1 anatomic location at 1 time point may be insufficient to treat patients with mCRC, as we recognize that there can be spatial tumor heterogeneity (between the primary tumor and metastatic lesions) and temporal tumor heterogeneity (when targeted therapies exert pressure for certain mutations to disappear and new mutations to evolve).3,4 The invasiveness of serial tissue biopsies and the turnaround time of 2 to 4 weeks for NGS analysis can both be limitations for clinical use. [...]the development of blood-based NGS testing as a method to analyze circulating tumor DNA (ctDNA) has been a welcome one. The Guardant360 CDX (Guardant Health, Redwood City, CA) assay has been FDA approved as a companion test for EGFR mutation for the use of osimertinib (Tagrisso) for patients with NSCLC. [...]blood-based NGS should be considered an additional test that clinicians can utilize in the care of patients with mCRC. For patients with previously treated BRAF V600E-mutant mCRC, the phase 3 BEACON CRC study (NCT02928224) found that combined inhibition of BRAF and EGFR with encorafenib (Braftovi) and cetuximab, respectively, led to improvements in OS, objective response rate (ORR), and progression-free survival (PFS) when compared with treatment with standard chemotherapy.22 Median OS, ORR, and PFS for the doublet arm were 9.3 months, 19.5%, and 4.3 months, compared with 5.9 months, 1.8%, and 1.5 months, respectively, for the control arm. The MyPathway phase 2 study utilized trastuzumab and pertuzumab (Perjeta) in a similar patient population, generating an ORR of 32%25; however, patients with KRAS-mutant disease were not excluded and tended to have lower response rates to dual anti-HER2 blockade.