Table 1.

Patient, treatment outcome, and resistance characteristics

PatientAge/sexBRAF genotypeM stageDrugRECIST response categoryaRECIST% responsePFS (weeks)OS (weeks)Prog No.SiteType of Prog lesionResistance mechanismMAPK activityc
151/MV600ECDabPR−7196.0203.6e1SQNewMEK1E203K+
240/FV600ECDabPR−6156.7113.7e1SQNewN-RASQ61K+
359/MV600KCDabPR−3246.989.41SQNewUnknown+
2SQNewUnknown+
431/MV600KCDabPR−8939.4103.9e1BowelNewBRAF exon 2-10Δ+
559/MV600KCDabSD−1432.037.01SQNaUnknown+
6b67/MV600EADabPR−4232.065.41LNNewBRAF amplificationna
771/MV600ECDabPR−6231.444.01LNExisting—RESBRAF exon 4-8Δ+
875/FV600ECDabPR−6730.180.71SQExisting—RESUnknown+
SQExisting—RESUnknown+
959/FV600ECDabPR−6329.9135.91SQExisting—RESBRAF exon 2-10Δ+
1033/FV600EADabPR−6029.9124.91SQNewIGF-IR
2SQNewBRAF exon 4-8Δ+
1139/FV600KCDabRES17.0124.91SQNaUnknown
2BrainNewAKT1Q79K+
1240/MV600KCDabPR−7116.977.61SQNewUnknown+
1331/MV600ECDabSD−516.730.61SQNaUnknownd
1463/MV600ECDabSD−2616.045.71BrainExisting—RESBRAF amplification+
1540/FV600ECDabPR−4316.022.01SQExisting—RESBRAF exon 2-10Δ & N-RASQ61Kna
1651/MV600KADabPR−3216.087.61SQexisting—RESUnknownna
17g17/MV600ECDabRES13.490.0e1LungExisting—RESUnknown+
1860/MV600ECDabSD−2512.128.41BowelExisting—RESUnknown
2SQNewMEK1K57E+
1958/MV600ECDabPR−4310.624.71LNExisting—RESUnknownna
2067/MV600KCDabRES9.028.61SQNewUnknownna
2155/FV600ECDabNo RES8.328.61BrainExisting—no RESUnknown
2275/MV600KCDabNo RES7.039.0e1BowelExisting—no RESBRAF exon 2-10Δ & 2-8Δna
2360/FV600ECVemPR−4432.032.91SQExisting—RESBRAF exon 2-8Δ+
2472/MV600ECVemPR−5329.994.31SQExisting—RESN-RASG13Rf+
2580/MV600KCVemPR−5824.973.6e1SQNaUnknown
2666/MV600ECVemPR−6823.646.71SQNewUnknownna
2753/FV600ECVemPR−4823.687.9e1SQNewBRAF exon 2-8Δna
2884/MV600RAVemRES22.045.4e1SQExisting—RESBRAF exon 2-8Δ+
2SQExisting—RESBRAF exon 4-8Δ+
3SQExisting—RESBRAF exon 2-8Δ+
4SQExisting—RESBRAF exon 4-8Δ+
2952/FV600ECVemPR−5416.0103.6e1SQnaBRAF amplificationna
3065/MV600ECVemSD−1715.332.11LungExisting—RESMEK2F57C+

Abbreviations: Dab, dabrafenib; Vem, vemurafenib; PR, partial response, SD, stable disease; RES, response; SQ, subcutaneous; LN, lymph node; na, data not available.

fThis Prog from patient 24 displayed two distinct subclones by p-ERK IHC (39).

gPatient 17 Pre and Prog tumors had nonsense mutations in the PTEN and CDKN2A genes.

  • aPatients without prospective RECIST assessments or measurable disease at baseline, response categorized as response (RES) or no response (no RES).

  • bBecause of high melanin content in Prog-derived RNA, only qPCR analyses of BRAF copy number was performed on this patient Prog tumor.

  • cMAPK activity was determined using GSEA of whole transcriptome data comparing matched pretreatment (n = 21) and Prog (n = 29) biopsies. + indicates re-activated and − indicates inhibited.

  • dAn AKT1 polymorphism (D46E; rs146875699) was identified in the Prog and matching pretreatment tumors of patient 13.

  • eAlive at the time of analysis.