. 2023 Mar 3;7(15):3984–3992. doi: 10.1182/bloodadvances.2022009013

Table 2.

Summary of treatment toxicity and response

Age at diagnosis (y)/sex	Histology	BRAF status	Other relevant molecular alterations	Involvement (sites of biopsies in bold)	Trametinib line of treatment	Clinically significant treatment-related toxicity	Best response ^†	Trametinib starting dosage	Trametinib ending dosage	Comments
25/F	ECD/RDD	Wild-type ^‡	MAP2K1^K57N, ASXL1^R965^∗	Skin, bone, heart valve, periaortic	1		CR	0.5 mg daily	0.5 mg daily
66/M	ECD/RDD	Wild-type ^‡	NRAS^Q61R	Bone, skin, lymph nodes, lung, dura, and orbit	3	Congestive heart failure	CR	1.5 mg daily	1 mg daily
36/M	ECD/RDD	Wild-type ^‡	ANP32A-BRAF fusion	Bone, omentum, mesentery, and retroperitoneum	3		SD	1.5 mg daily	0.5 mg daily
53/M	ECD/RDD	Wild-type ^‡	MAP2K1^F53L	Bone, pleura, and retroperitoneum	1	Fatigue	PR	0.5 mg daily	0.5 mg daily
69/M ^∗	ECD/LCH	Wild-type ^‡	MAP2K1^C121S	Brain, bones, retroperitoneum, and periaortic	2	Fatigue	PR	1.5 mg daily	0.5 mg daily
49/M ^∗	ECD	Wild-type ^‡	MAP2K1^Q56P	Heart, retroperitoneum, pituitary, bones, and skin	4	Rash	SD	1 mg daily	0.5 mg daily
55/M	ECD	BRAF^V600E	None identified	CNS, adrenal gland, aorta, and perinephric	2	Facial acne (rash), chills, rigors, and drug-induced hepatitis	PR	2 mg daily	2 mg daily
38/F	ECD	BRAF^V600E^§^‡	BRAF^V471F-NF1 splice site mutations, MCL1 amplification	CNS, soft tissue, and bone	4	Paronychia and xerosis	SD	2 mg daily	2 mg daily
44/M	ECD/RDD	BRAF^V600E^§^‖	MAP2K1	Eye, vocal cord, periaortic, bone, and sinuses	3	Facial acne (rash)	IE	2 mg daily	2 mg daily	IE for response because of treatment discontinuation before the first on-treatment assessment
59/M	ECD	Wild-type	None identified	Perinephric, bone, and aorta	3	Rash and diarrhea	IE	2 mg daily	2 mg daily	IE because of treatment discontinuation before the first on-treatment assessment
36/M	ECD	Wild-type	None identified	Bone and skin	3		IE	1 mg daily	1 mg daily	IE for response because of lack of measurable disease
41/M	ECD	Wild-type	None identified	Eyelid	3		IE	2 mg daily	1.5 mg daily	IE for response because of lack of measurable disease
60/M	ECD	BRAF^V600E^‡^‖	ASXL1^E635fs^∗¹⁵ and CCNE1^P396L	Pericardial, perinephric, bone, retroperitoneal, and lymph node	1		PR	1 mg daily	1 mg daily
49/M	ECD	BRAF^V600E^‡^‖	ASXL1^G646fs^∗¹², BRAF^L485W, and ERBB2 amplification	Bone, kidney, abdomen, and lung	From 1 to 5 (varied with and without dabrafenib and anakinra)	Pneumonia	PR	1 mg daily	1 mg daily
40/F	ECD	Wild-type	No additional molecular testing performed	Bone and brain	1	Nausea	PR	1 mg daily	1.5 mg daily
23/F	RDD	CAPZA2-BRAF fusion ^‡^‖	IDH2^A47V and RAF1 amplification	Brain	1	Mucositis and rash	IE	2 mg every other day	2 mg daily	IE for response because of loss to follow-up
28/F	RDD	Wild-type ^‖	APC^E1157fs	Breast and thigh	1	Facial acne (rash)	IE	1 mg daily	1 mg daily	IE for response because of loss to follow-up
69/F	RDD	Wild-type ^‖	GNAS^R201C	Ear and eye	1		SD	1 mg daily	1.5 mg daily
66/M	ECD	Wild-type ^‖	STK11 (splice site SNV)	Bone, aorta, and peritoneum	3		IE	1 mg daily		IE for response because of loss follow-up
49/F	ECD	BRAF^V600E^‡	NF1^H1494Y	Bone, abdomen, and kidney	3	Rash and dizziness	IE	0.5 mg daily (1 week)	1 mg daily	IE because of treatment discontinuation before the first on-treatment assessment; trametinib used with dabrafenib
56/M	ECD	BRAF^V600E	No additional molecular testing performed	Bone and peritoneum	4	Renal toxicity	PR	0.5 mg daily	0.5 mg daily	Trametinib used with vemurafenib
52/M	ECD	BRAF^V600E^‡	NF1^S1407R, NRAS^G60R, KRAS^A59T	Bone, kidney, abdomen, and lung	2	Uveitis	SD	0.5 mg daily	0.5 mg every other day
29/F	ECD	Wild-type ^‡	MAP2K1^Q65P	Bone and pericardium	3		PR	0.5 mg daily	0.5 mg daily
77/M	ECD	BRAF^V600E	None identified	Bone, aorta, and peritoneum	2	Congestive heart failure	IE	2 mg daily	2 mg daily	IE because of treatment discontinuation before the first on-treatment assessment; trametinib used with dabrafenib
53/M	ECD	Wild-type ^‡	GNAS^R201S	Bone and lung	1	Mucositis and infection	PR	1 mg daily	0.5 mg daily
59/M	ECD	Wild-type ^‡	KRAS^A146P, RB1^S249, and GNAS^Q227E	Bone, kidney, abdomen, lung	1		PR	0.5 mg daily	0.5 mg daily

CNS, central nervous system; CR, complete response; F, female; IE, inevaluable; M, male; PD, progressive disease; PR, partial response; SD, stable disease; SNV, single nucleotide variant.

^∗

Patient deceased.

^†

CR indicates resolution of lesions, PR indicates improvement but not resolution, SD indicates no change, PD indicates progressive or new lesions, and IE indicates patients in whom response could not be evaluated, and reasons are listed in “Comments.”

^‡

Tissue-targeted NGS in CLIA-certified lab, including MSK-IMPACT, MD Anderson Oncomine, Foundation One and others.

^§

Urine cell-free DNA

^‖

Plasma-targeted NGS in CLIA-certified lab, including Guardant 360, Foundation Liquid CDx and others. (polymerase chain reaction–based testing for BRAF V600E for others)