Table 3:
Patients with non-standard BRAF alterations
| ID | Age | Gender | Diagnosis | BRAF alteration (Class) | Other Alterations | TMB | Drug | Line of Therapy | Best Response | PFS Months** | OS Months** |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 41 | F | colon cancer | D594G (III) | KIT D737N, APC R1399fs*9, BRIP1 I550fs*40, FLCN R477*, TP53 H179R | 9 | trametinib | 3+ | PR | 11.66+ | 13.63+ |
| 2 | 83 | M | lung adenocarcinoma | D594H (III), G466A (III) | EGFR exon 19 deletion, BAP1 loss, CDKN2A/B loss, RB1 splice site 2107–1_2113delGATTATGA | 3 | dabrafenib, trametinib | 2 | SD <6 months | 3.15 | 20.83+ |
| 3 | 40 | F | small bowel adenocarcinoma | D594N (III) | KRAS E63K, RAF1 S257L, SMAD4 R361H, W509*, SOX9 Q393fs*12, TP53 A86fs*38 | 4 | trametinib | 1 | PD | 1.58 | 3.52 |
| 4 | 84 | F | melanoma | G469A (II) | PTEN loss exons 3–9, CDKN2A/B loss, TERT promoter-124C>T | 18 | dabrafenib, trametinib | 3+ | PR | 4.34 | 4.34 |
| 5 | 66 | M | non-small cell lung cancer | K601E (II) | TP53 G154V, SPTA1 E1469fs*11 | N/A* | vemurafenib | 2 | PR | 5.26 | 5.78 |
| 6 | 79 | F | melanoma | N581S(III) | CDK4 amp, ERBB3 amp, MDM2 amp, TET2 splice site 4044+1G>T, T1895fs*13 | 8 | dabrafenib, trametinib | 2 | PD | 0.39 | 0.53 |
| 7 | 75 | F | pancreatic cancer | V600_K601>E (I***) | TP53 V218E | 4 | Trametinib | 2 | SD ≥ 6 months | 6.05 | 8.87 |
| 8 | 64 | M | melanoma | V600R (I) | FLT1 S287F, PTEN Q214fs*5, CDKN2A loss p16INK4a and p14ARF exons 2–3, TP53 E198K, LRP1B R295*, LRP1B R3186C | N/A* | dabrafenib, trametinib | 2 | PR | 3.15 | 3.15 |
N/A: tumor mutational burden was not available for these Foundation Medicine reports from 2014
+ indicates patient was censored prior to event occurrence
V600_K601>E found to constitutively activate the B-Raf kinase and the MAP kinase pathway, similar to the classical BRAF V600E mutation (35)
Abbreviations: F=female, M=male, OS=Overall Survival, PD=progressive disease, PFS=progression free survival, PR=partial response, SD=stable disease, TMB=tumor mutational burden (Mutations/Megabase), 3+=3 or more lines of therapy