Table 2.
Analysis of biomarker testing by landmark time point (online only)
| Time periods | % tested | Comparison | P |
|---|---|---|---|
| NRAS | |||
| Period 1: January 1, 2013, to TP 1 | 4.10 | Referent | |
| [September 12, 2013, landmark publication—NRAS MT predictive of EGFR inhibitor response (6)] | |||
| Period 2: TP 1 to TP 2 | 3.82 | Period 1 vs period 2 | .69 |
| [January 1, 27, 2014, NCCN guideline update recommends universal NRAS and KRAS testing in mCRC (32)] | |||
| Period 3: TP 2 to TP 3 | 23.45 | Period 2 vs period 3 | <.001 |
| [June 17, 2017, FDA label change—EGFR inhibitor only indicated in RAS WT mCRC (33,54)] | |||
| Period 4: TP 3 to June 30, 2018a | 42.78 | Period 3 vs period 4 | <.001 |
| BRAF | |||
| Period 1: January 1, 2013, to TP 1 | 11.54 | Referent | |
| [August 20, 2014, NCCN guideline update recommends universal KRAS, NRAS, and BRAF testing in mCRC (34)] | |||
| Period 2: TP 1 to TP 2 | 23.96 | Period 1 vs period 2 | <.001 |
| [May 20, 2017, landmark publication—BRAF v600E MT predictive of BRAF inhibitor response (35)] | |||
| Period 3: TP 2 to TP 3 | 40.14 | Period 2 vs period 3 | <.001 |
| [January 18, 2018, NCCN guideline update recommends EGFR inhibitor only in combination with BRAF inhibitor in BRAF v600E mutated mCRC (25)] | |||
| Period 4: TP 3 to June 30, 2018 | 45.85 | Period 3 vs period 4 | <.001 |
| MMR/MSI | |||
| Period 1: January 1, 2013, to TP 1 | 23.29 | Referent | |
| [June 25, 2015, landmark publication—MMR predictive of PD-1 mAb response (36)] | |||
| Period 2: TP 1 to TP 2 | 32.01 | Period 1 vs period 2 | <.001 |
| [November 23, 2015, NCCN guideline update recommends MMR/MSI testing in all CRC (55)] | |||
| Period 3: TP 2 to TP 3 | 42.92 | Period 2 vs period 3 | <.001 |
| [July 31, 2017, FDA label change—nivolumab approved for dMMR/MSI-H mCRC (56)] | |||
| Period 4: TP 3 to June 30, 2018 | 59.31 | Period 3 vs period 4 | <.001 |
a
June 30, 2018, marks the end of available data. CRC = colorectal cancer; EGFR = epidermal growth factor receptor; FDA = Food and Drug Administration; mAb = monoclonal antibody; mCRC = metastatic colorectal cancer; MMR = mismatch repair; MSI = microsatellite instability; MSI-H = microsatellite instability high; dMMR- deficient mismatch repair; MT = mutated; NCCN = National Comprehensive Cancer Network; PD-1 = programmed death ligand 1; TP = time point; WT = wild type.