. 2015 Nov 25;1(2):73–82. doi: 10.1200/JGO.2015.000802

Table 2.

Baseline Patient Characteristics and Number of Adverse Events in Each Trial

Study	Year	Quality (Jadad score)	Study Type	Cancer Type	Treatment Regimen (No. of patients)	Baseline Patient Characteristics	Indication	Decreased Ejection Fraction	Hypertension
Study	Year	Quality (Jadad score)	Study Type	Cancer Type	Treatment Regimen (No. of patients)	Baseline Patient Characteristics	Indication	Decreased Ejection Fraction	All-Grade	High-Grade
Trametinib studies
Flaherty et al¹⁶	2012	3 (open-label)	Phase III RCT	Melanoma	Arm A: trametinib 2 mg orally once per day (211 patients) Arm B: intravenous chemotherapy consisting of either dacarbazine 1,000 mg/m² or paclitaxel 175 mg/m² once every 3 weeks (99 patients)	Median age: 55 (23-85) v 54 (21-77) Male sex: 120 (56%) v 53 (49%) White race: 214 (100%) v 108 (100%)	First-line therapy for cutaneous advanced or metastatic melanoma (stage IIIC or IV) with a BRAF V600 mutation-positive tumor sample	11 patients (5.2%) in the trametinib arm only	32 (15%) v 7 (7%)	26 (12%) v 3 (3%)
Robert et al²³	2015	3 (open-label)	Phase III RCT	Melanoma	Arm A: combination of dabrafenib 150 mg twice per day and trametinib 2 mg once per day (350 patients) Arm B: vemurafenib 960 mg orally twice per day (349 patients)	Median age: 55 (18-91) v 54 (18-88) Male sex: 208 (59%) v 180 (51%)	First-line therapy for cutaneous advanced or metastatic melanoma (stage IIIC or stage IV) with a BRAF V600 mutation-positive tumor sample	29 patients (8%) in arm A only	92 (26.3%) v 85 (24.4%)	N/R
Long et al²¹	2014	5	Phase III RCT	Melanoma	Arm A: combination of dabrafenib 150 mg orally twice per day and trametinib 2 mg orally once per day (209 patients) Arm B: dabrafenib and placebo (211 patients)	Median age: 55 (22-89) v 56.5 (22-86) Male sex: 111 (53%) v 114 (54%)	First-line therapy for cutaneous advanced or metastatic melanoma (stage IIIC or stage IV) with a BRAF V600 mutation-positive tumor sample	9 (4%) v 5 (2%)	46 (22%) v 29 (14%)	8 (4%) v 10 (5%)
Flaherty et al¹⁵	2012	3 (open-label)	Phase III RCT	Melanoma	Arm A: dabrafenib monotherapy 150 mg orally once per day (55 patients) Arm B: combination of dabrafenib 150 mg orally twice per day and trametinib 1 mg orally once per day (54 patients) Arm C: combination of dabrafenib 150 mg orally twice per day and trametinib 2 mg orally once per day (55 patients)	Median age: 50 (18-82) v 49 (23-85) v 58 (27-79) Male sex: 29 (54%) v 30 (56%) v 34 (63%)	First-line therapy for patients with BRAF-mutant metastatic melanoma	0 v 2 (4%) v 5 (9%)	2 (4%) v 2 (4%) v 5 (9%)	1 (2%) patient in arm C only
Infante et al²⁰	2014	5	Phase II RCT	Pancreas	Arm A: trametinib 2 mg per day plus intravenous gemcitabine 1,000 mg/m² once per week for 8 weeks, then days 1, 8, and 15 of 28-day cycles (80 patients) Arm B: placebo plus intravenous gemcitabine 1,000 mg/m² once per week for 8 weeks, then days 1, 8, and 15 of 28-day cycles (80 patients)	Median age: 64 (42-85) v 63.5 (41-82) Age group ≥ 65: 39 (49%) v 34 (43%) Male sex: 39 (49%) v 46 (58%) White/European heritage: 50 (63%) v 59 (74%)	First-line therapy for untreated metastatic adenocarcinoma of the pancreas	7 (8.8%) v 2 (2.5%)	2 (2.5%) v 6 (7.5%)	N/R
Blumenschein et al⁸	2015	3 (open-label)	Phase II RCT	NSCLC	Arm A: trametinib 2 mg orally once per day (87 patients) Arm B: docetaxel 75 mg/m² intravenously once every 3 weeks (43 patients)	Median age: 63 (40-79) v 63 (34-79) Male sex: 46 (53%) v 23 (53%) White race: 74 (87%) v 34 (79%) Smoking status: current: 13 (15%) v 13 (30%); former: 67 (78%) v 23 (53%)	Second-line therapy for histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy	5 patients (5.8%) in arm A only	13 (15%) v 1 (2%)	8 (9%) grade 3 events in arm A only
Selumetinib studies
Robert et al²²	2013	5	Phase II RCT	Melanoma	Arm A: intravenous dacarbazine 1,000 mg/m² on day 1 of a 21-day cycle plus oral selumetinib 75 mg twice per day on a 21-day cycle (44 patients) Arm B: intravenous dacarbazine 1,000 mg/m² on day 1 of a 21-day cycle plus placebo (45 patients)	Median age: 57 (48-69) v 52 (40-65) Male sex: 22 (49%) v 28 (61%)	First-line treatment for BRAF-mutant metastatic melanoma	7 (16%) v 1 (2%)	N/R
Kirkwood et al¹⁷	2012	3 (open-label)	Phase II RCT	Melanoma	Arm A: oral selumetinib 100 mg twice per day on 28-day cycles (99 patients) Arm B: oral temozolomide 200 mg/m² per day for 5 days, then 23 days off treatment (95 patients)	Mean age: 57.1 (20-84) v 57 (28-84) Male sex: 55 (52.9%) v 65 (67.7%) White race: 99 (95.2%) v 91 (94.8%)	Chemotherapy-naive patients with unresectable stage III to IV melanoma	N/R	8 (8.1%) v 2 (2.1%)
Zaman et al¹⁸	2015	5	Phase II RCT	Breast	Arm A: fulvestrant 500 mg intramuscularly on days 1, 15, and 29 of cycle 1 and then every 28 ± 3 days plus selumetinib 75 mg orally twice per day (23 patients) Arm B: fulvestrant 500 mg intramuscularly on days 1, 15, and 29 of cycle 1 and then every 28 ± 3 days plus placebo (22 patients)	Median age: 66 (40-79) v 69 (46-79); all included patients were postmenopausal women	Second-line treatment in postmenopausal women with advanced-stage endocrine sensitive breast cancer	N/R	All-grade: 5 (23%) v 5 (24%) High-grade: 1 (4.3%) v 2 (9.1%)
Cobimetinib studies
Larkin et al¹⁹	2014	4 (blinding method was not described)	Phase III RCT	Melanoma	Arm A: oral vemurafenib 960 mg twice per day together with cobimetinib 60 mg once per day for 21 days, followed by 7 days off treatment (254 patients) Arm B: oral vemurafenib 960 mg twice per day together with placebo (239 patients)	Median age: 56 (23-88) v 55 (25-85) Male sex: 146 (59%) v 140 (56%) White race: 227 (92%) v 235 (95%)	First-line therapy for cutaneous advanced or metastatic melanoma (stage IIIC or IV) with a BRAF V600 mutation-positive tumor sample	19 (7.5%) v 7 (2.9%)	N/R

NOTE: Age is provided in years; range is in following parentheses.

Abbreviations: N/R, not reported; NSCLC, non–small-cell lung cancer; RCT, randomized controlled trial.