Table 1.

Acquired alterations in BRAF V600E colorectal cancers treated with RAF/EGFR inhibitor combinations

PatientTreatmentBest response (RECIST read)Duration of responseAcquired ERK pathway alteration
1Vemurafenib + PanitumumabPR (−100%)40 weeksNRAS Q61K
2Vemurafenib + PanitumumabPR (−64%)24 weeksBRAF V600E amplification (predominantly double minute chromosomes with 10–100 copies of BRAF)
3Encorafenib + Cetuximab + AlpelisibPR (−62%)24 weeksPeritoneal metastasis: BRAF del exons 2–8
Liver metastasis: NRAS G13R
4Vemurafenib + CetuximabPR (−50%)16 weeksBRAF V600E amplification (predominantly clusters of 6–14 copies of BRAF)
5Encorafenib + Cetuximab + AlpelisibPR (−43%)18 weeksKRAS G12A
6Vemurafenib + PanitumumabSD (−24%)32 weeksKRAS gain (4 copies), MET gain (5 copies)
7Vemurafenib + PanitumumabSD (−20%)16 weeksNRAS amplification (>10 copies)
8Vemurafenib + CetuximabSD (−10%)24 weeksKRAS amplification (predominantly homologous staining region type with 10 to >20 copies of KRAS)
  • NOTE: Vemurafenib + panitumumab treatment was given in a pilot trial (16), encorafenib + cetuximab + alpelisib was given in a phase Ib/II trial (15), and vemurafenib + cetuximab treatment was given in the basket trial of vemurafenib (14).

  • Abbreviations: PR, partial response; SD, stable disease.