ライフサイエンスコーパス: vemurafenib

1 he cells more resistant to targeted therapy (vemurafenib).

2 ical responses when chloroquine was added to vemurafenib.

3 tiation of treatment with the BRAF inhibitor vemurafenib.

4 isted even 732 days after discontinuation of vemurafenib.

5 han one-fifth of patients being treated with vemurafenib.

6 OR pathway inhibition by the B-Raf inhibitor vemurafenib.

7 al600Glu are sensitive to the BRAF inhibitor vemurafenib.

8 roquinolones ciprofloxacin and ofloxacin and vemurafenib.

9 l patients who received at least one dose of vemurafenib.

10 dacarbazine crossed over from dacarbazine to vemurafenib.

11 first studied 20 melanoma patients receiving vemurafenib.

12 quired resistance to BRAF inhibitors such as vemurafenib.

13 f melanoma cells with acquired resistance to vemurafenib.

14 e of melanoma cells chronically treated with vemurafenib.

15 ration BRAF inhibitor and research analog of vemurafenib.

16 dermatitis, suggesting radiosensitization by vemurafenib.

17 aling to overcome the acquired resistance to vemurafenib.

18 tance and sensitivity to the BRAF inhibitor, vemurafenib.

19 entifying mutations conferring resistance to Vemurafenib.

20 suggested disease acceleration triggered by vemurafenib.

21 but lacked sensitivity to the BRAF inhibitor vemurafenib.

22 Photosensitivity was more common with vemurafenib (14 patients [38.9%]) compared with dabrafen

23 of BRAF V600E downstream targets showed that vemurafenib (480 mg/d) completely abrogated extracellula

24 lation phase of our study, patients received vemurafenib 720 mg or 960 mg twice a day continuously an

25 Patients received vemurafenib 960 mg orally twice daily.

26 on of QTc; and two patients on a schedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg 28/

27 re than 7 days; one patient on a schedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg onc

28 One patient on a schedule of vemurafenib 960 mg twice a day and cobimetinib 80 mg onc

29 he maximum tolerated dose was established as vemurafenib 960 mg twice a day in combination with cobim

30 noma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day.

31 e voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (

32 e daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as first-line th

33 cycle) or placebo, in combination with oral vemurafenib (960 mg twice daily).

34 57 (BRIM-2), patients received oral doses of vemurafenib (960 mg twice per day).

35 Mutant ARAF activity was inhibited by vemurafenib, a BRAF inhibitor, indicating the importance

36 elanomas and their associated sensitivity to vemurafenib, a BRAF inhibitor.

37 A-Raf molecule is sensitive to inhibition by vemurafenib, a potent and selective Raf kinase inhibitor

38 a developed EMN while receiving therapy with vemurafenib, a selective BRAF inhibitor.

39 Vemurafenib, a selective inhibitor of RAF kinases, has c

40 Vemurafenib, a specific BRAF(V600E) inhibitor, has signi

41 enes whose loss is involved in resistance to vemurafenib, a therapeutic RAF inhibitor.

42 ioprine, the fluoroquinolone antibiotics and vemurafenib-a BRAF inhibitor used to treat metastatic me

43 nase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing.

44 Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing t

45 rally bioavailable B-Raf inhibitors, such as vemurafenib, achieve dramatic responses initially, but t

46 ue of the JCI, Ma and colleagues report that vemurafenib activates ER stress and autophagy in BRAF(V6

47 Preliminary vemurafenib activity was observed in non-small-cell lung

48 ch drug resistance is selected by continuous vemurafenib administration.

49 ession-free survival than those treated with vemurafenib alone.

50 Vemurafenib, an oncogenic BRAF kinase inhibitor approved

51 Vemurafenib, an oral BRAF V600 inhibitor, has pronounced

52 Hypokalemia (6 cases in patients receiving vemurafenib and 2 cases in patients receiving dabrafenib

53 n the trials: 568 patients were treated with vemurafenib and 287 patients were treated with dacarbazi

54 7 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine.

55 d cobimetinib: 66 had recently progressed on vemurafenib and 63 had never received a BRAF inhibitor.

56 follow-up was 12.5 months (IQR 7.7-16.0) on vemurafenib and 9.5 months (3.1-14.7) on dacarbazine.

57 nib-resistant melanoma with a combination of vemurafenib and an autophagy inhibitor reduced tumor loa

58 patients with colorectal cancer who received vemurafenib and cetuximab.

59 patients with colorectal cancer who received vemurafenib and cetuximab.

60 F V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemur

61 Vemurafenib and cobimetinib was associated with a nonsig

62 The combination of vemurafenib and cobimetinib was safe and tolerable when

63 All patients treated with vemurafenib and cobimetinib were included in safety and

64 ere treated at ten dosing regimens combining vemurafenib and cobimetinib: 66 had recently progressed

65 The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monoth

66 The selective BRAF inhibitors vemurafenib and dabrafenib have shown significant improv

67 PK) confers resistance to the RAF inhibitors vemurafenib and dabrafenib in mutant BRAF-driven melanom

68 neous adverse effects of the BRAF inhibitors vemurafenib and dabrafenib mesylate in the treatment of

69 low-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the

70 Vemurafenib and dabrafenib selectively inhibit the v-Raf

71 n are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune su

72 The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical

73 selective inhibitors of mutant BRAF Val600, vemurafenib and dabrafenib, showed major tumour response

74 The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF

75 sole BRAF inhibition with the BRAF inhibitor vemurafenib and may provide a novel targeted therapeutic

76 nd efficacy of combined BRAF inhibition with vemurafenib and MEK inhibition with cobimetinib in patie

77 vents of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no

78 fenib and cobimetinib (combination group) or vemurafenib and placebo (control group).

79 re unresponsive to both generations of RAFi, vemurafenib and PLX8394, highlighting a distinct respons

80 linical benefit of cobimetinib combined with vemurafenib and support the use of the combination as a

81 fit over monotherapy with the BRAF inhibitor vemurafenib and supports the combination therapy as stan

82 the Food and Drug Administration approval of vemurafenib and the development of other RAF and MEK (mi

83 luated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.

84 o combined treatment with the BRAF inhibitor vemurafenib and the mitogen-activated protein kinase/ext

85 s of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combination

86 Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation

87 by showing that the RAF inhibitors PLX-4032 (vemurafenib) and GDC-0879 precipitate the development of

88 effects are recapitulated by B-Raf (PLX4720, vemurafenib, and dabrafenib) or MEK inhibitors (trametin

89 partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standar

90 these, 119 patients received dabrafenib; 36, vemurafenib; and 30, CombiDT therapy.

91 /relapsed HCL patients to the BRAF inhibitor vemurafenib approached 100%, with 35% to 40% complete re

92 ing in patients receiving the BRAF inhibitor vemurafenib, as well as 10 normal skin samples, to ident

93 Acquired resistance to vemurafenib associated with reactivation of MAPK signali

94 al signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-H

95 hase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily)--one in It

96 s, ectopic CK2alpha decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor

97 However, vemurafenib can be continued while the ocular symptoms a

98 Selective BRAF inhibitors such as vemurafenib cause multiple cutaneous adverse effects, in

99 Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous

100 The vemurafenib clinical trials were a multicenter series in

101 The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved r

102 Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatmen

103 nce of cutaneous toxic effects differs among vemurafenib, dabrafenib, and CombiDT therapies.

104 wed further exploration into the novel drugs vemurafenib, dabrafenib, trametinib, and ibrutinib.

105 om 26 patients to clinically available BRAF (vemurafenib; dabrafenib) or MEK (trametinib) inhibitors.

106 pproximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (c

107 ith BRAF V600E-mutant melanoma, single-agent vemurafenib did not show meaningful clinical activity in

108 At the same time, vemurafenib directly activated the fibroblasts through p

109 Here, we examine how vemurafenib disposition, particularly through cytochrome

110 ration selective BRAF inhibitor that, unlike vemurafenib, does not induce activation of wild-type BRA

111 Patients' demographics, vemurafenib dosages, and the intervals between the onset

112 The vemurafenib dose was 960 mg twice per day in 6 patients

113 and kinetics of response were independent of vemurafenib dosing.

114 riven melanoma respond to the BRAF inhibitor vemurafenib due to subsequent deactivation of the prolif

115 ll lines, A375 and DM443, by serial in vitro vemurafenib exposure.

116 y stimulated Ras and MAPK upregulation after vemurafenib exposure.

117 clib, suggesting that initial treatment with vemurafenib followed by palbociclib with or without mTOR

118 rradiated skin area in patients treated with vemurafenib for a BRAFV600-mutated metastatic melanoma.

119 fety was similar to that in prior studies of vemurafenib for melanoma.

120 the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should b

121 evaluated tumors from patients treated with vemurafenib for the presence of human papilloma virus (H

122 anoma was initiated on twice-daily 960 mg of vemurafenib for treatment of progressive and recurrent s

123 the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous mel

124 hibited by targeted therapies (e.g. PLX-4032/vemurafenib), glucose metabolism is reduced, and cells i

125 rapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combina

126 bination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0

127 nd randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo plus vemurafenib gr

128 us vemurafenib group (n=247) or placebo plus vemurafenib group (n=248).

129 the combination-therapy group and 51% in the vemurafenib group (P<0.001).

130 nts: 109 (93%) of 117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 in the vemurafeni

131 have died: 117 (47%) in the cobimetinib and vemurafenib group and 142 (58%) in the vemurafenib group

132 in 92 patients (37%) in the cobimetinib and vemurafenib group and 69 patients (28%) in the vemurafen

133 ormal liver function tests (38 [11%]) in the vemurafenib group and neutropenia (26 [9%] of 287 patien

134 Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine grou

135 frequency in patients in the cobimetinib and vemurafenib group compared with the vemurafenib group we

136 all survival was significantly longer in the vemurafenib group than in the dacarbazine group (13.6 mo

137 se increase (36 [15%] in the cobimetinib and vemurafenib group vs 25 [10%] in the placebo and vemuraf

138 00E) disease, median overall survival in the vemurafenib group was 13.3 months (95% CI 11.9-14.9) com

139 00K) disease, median overall survival in the vemurafenib group was 14.5 months (95% CI 11.2-not estim

140 inib and vemurafenib group compared with the vemurafenib group were gamma-glutamyl transferase increa

141 rafenib group vs 25 [10%] in the placebo and vemurafenib group), blood creatine phosphokinase increas

142 nation-therapy group and 18% of those in the vemurafenib group.

143 emurafenib group and 133 (94%) of 142 in the vemurafenib group.

144 murafenib group and 69 patients (28%) in the vemurafenib group.

145 b and vemurafenib group and 142 (58%) in the vemurafenib group.

146 verse events reported in the cobimetinib and vemurafenib group.

147 Vemurafenib has an objective and sustained efficacy in B

148 In particular, the selective BRAF inhibitor vemurafenib has been shown to improve overall survival i

149 veral small molecule BRAF inhibitors such as vemurafenib have been developed and demonstrate remarkab

150 Preclinical models of resistance to vemurafenib have provided critical insights into predict

151 Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-

152 versus 7.2 months (5.6-7.5) for placebo and vemurafenib (HR 0.58 [95% CI 0.46-0.72], p<0.0001).

153 .4 months (95% CI 15.0-19.8) for placebo and vemurafenib (HR 0.70, 95% CI 0.55-0.90; p=0.005).

154 The combination of cobimetinib with vemurafenib improves progression-free survival compared

155 Inhibition of BRAF with vemurafenib improves survival in patients with the most

156 d therapy with an inhibitor of mutated BRAF (vemurafenib) improves survival of patients with melanoma

157 n associated with major clinical response to vemurafenib in a patient with metastatic melanoma.

158 tology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma c

159 ls testing selective BRAF inhibitors such as vemurafenib in BRAF(V600E)-mutant patients.

160 or, profoundly reduced circulating levels of vemurafenib in humanized mice.

161 e major enzyme involved in the metabolism of vemurafenib in in vitro assays with human liver microsom

162 wed the initial success of the RAF inhibitor vemurafenib in mutant V600 BRAF melanoma patients.

163 We assessed vemurafenib in patients with advanced metastatic melanom

164 We aimed to establish the activity of vemurafenib in patients with BRAF(V600E)-positive papill

165 fety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that ha

166 xclusive with KRAS and define sensitivity to vemurafenib in PDA models.

167 sion-free survival compared with placebo and vemurafenib in previously untreated patients with BRAF(V

168 ategy to overcome the acquired resistance to vemurafenib in the treatment of melanoma.

169 Topical treatment with vemurafenib in two wound-healing mice models accelerates

170 ted short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD.

171 he single-agent BRAF inhibitor dabrafenib or vemurafenib included Grover disease (51 patients [42.9%]

172 Inhibition of BRAF(V600E) using vemurafenib, independently of its cytostatic effects, su

173 ced apoptosis and melanoma cells to UVB- and vemurafenib-induced apoptosis.

174 Herein, a case of severe vemurafenib-induced granulomatous hepatitis leading to c

175 Bisected vemurafenib-induced lesions revealed surprising heteroge

176 requent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC.

177 Results Vemurafenib inhibited MAPK signaling and cell-cycle prog

178 spliced, truncated BRAF(V600E) that promotes vemurafenib-insensitive MAPK pathway signaling.

179 Vemurafenib is a potent RAF kinase inhibitor with remark

180 Vemurafenib is a revolutionary treatment for melanoma, b

181 armacodynamic interaction between x-rays and vemurafenib is also seen with other BRAF or MEK inhibito

182 noma cells treated with the kinase inhibitor vemurafenib is driven by downregulation of the transcrip

183 Dose reduction or interruption of vemurafenib is not required.

184 aken together, our findings demonstrate that vemurafenib is unlikely to exhibit a clinically signific

185 Retreatment with vemurafenib led to similar response patterns (n = 6).

186 athways may contribute more significantly to vemurafenib metabolism in vivo.

187 e-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy (960 mg twice-daily) orally as f

188 l in favour of the combination compared with vemurafenib monotherapy for most domains across all thre

189 Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall

190 ned to dabrafenib plus trametinib (n=352) or vemurafenib (n=352).

191 with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies.

192 Among the 568 patients treated with vemurafenib, ocular adverse effects developed in 22% (95

193 d CRAF isoforms with similar affinity, while vemurafenib or dabrafenib have little or modest CRAF act

194 iduals who had either recently progressed on vemurafenib or never received a BRAF inhibitor.

195 d the course of 21 HCL patients treated with vemurafenib outside of trials with individual dosing reg

196 In tumors with wild-type B-Raf, vemurafenib paradoxically activates downstream signaling

197 ed acquired resistance to the BRAF inhibitor vemurafenib (PLX-4032) and acted as a systemically deliv

198 re we show an unexpected and novel effect of vemurafenib/PLX4720 in suppressing apoptosis through the

199 ompetitive, first-generation RAF inhibitors (vemurafenib/PLX4720, RAFi) cause paradoxical activation

200 t alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, sug

201 s, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, inclu

202 noma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common

203 erized a novel ZNF767-BRAF fusion found in a vemurafenib-refractory respiratory tract PMM, from which

204 uman melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth in v

205 aive BRAF-mutant LAs and those with acquired vemurafenib resistance caused by an alternatively splice

206 nome expression analysis and discovered that vemurafenib resistance correlated with the loss of micro

207 We developed a CRAF-mediated model of vemurafenib resistance in melanoma cells to assess the i

208 ression and dysregulation is a mechanism for vemurafenib resistance in melanoma.

209 previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cel

210 the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells t

211 Here, we found that EGFR-induced vemurafenib resistance is ligand dependent.

212 ata highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of op

213 iRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM4

214 we investigate the cause and consequences of vemurafenib resistance using two independently derived p

215 The acquisition of vemurafenib resistance was associated with significantly

216 An inverse relationship between MITF, vemurafenib resistance, and EGFR was then observed in pa

217 a cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-

218 h pre-mRNA splicing as a mechanism to combat vemurafenib resistance.

219 s a novel, druggable target in CRAF-mediated vemurafenib resistance.

220 , induced MAP kinase signaling and conferred vemurafenib resistance.

221 drug-naive lines, two of which are innately vemurafenib resistant.

222 of MITF in drug response is corroborated in vemurafenib-resistant biopsies, including MITF-high and

223 f GMPR accompanies downregulation of MITF in vemurafenib-resistant BRAF(V600E)-melanoma cells and und

224 We tested this hypothesis in vemurafenib-resistant brain tumors.

225 The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem,

226 on of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vem

227 Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor

228 own of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with b

229 production and limit in-vitro cell growth of vemurafenib-resistant cells.

230 In preclinical studies, treating vemurafenib-resistant melanoma with a combination of vem

231 Most importantly, we demonstrate that vemurafenib-resistant melanomas become drug dependent fo

232 provide an avenue to overcome recurrence of vemurafenib-resistant metastatic disease.

233 A key observation has been that vemurafenib-resistant tumor cells suffer a fitness defic

234 Strikingly, we found that vemurafenib-resistant tumors remain sensitive to palboci

235 revents tumour formation and slows growth of vemurafenib-resistant tumours.

236 of Hsp90 and BRAF signaling using 17-AAG and vemurafenib, respectively.

237 not find information in the literature about vemurafenib response for rare and/or atypical BRAF mutat

238 ntribute to sustaining the durability of the vemurafenib response with the ultimate goal of curative

239 nvolved amino acids are important to predict vemurafenib response.

240 nib-resistant cells was determined to impact vemurafenib response.

241 ns for mechanism-based strategies to improve vemurafenib responses.Significance: Identification of mi

242 Vemurafenib safety in this diverse population of patient

243 3222 patients received at least one dose of vemurafenib (safety population).

244 Vemurafenib seems to be more nephrotoxic than dabrafenib

245 P1066, resulted in growth inhibition in both vemurafenib-sensitive and -resistant melanoma cells.

246 pparent mechanisms of acquired resistance in vemurafenib-sensitive patient-derived xenograft models.

247 ent a viable therapeutic strategy to restore vemurafenib sensitivity, reducing or even inhibiting the

248 Vemurafenib should be considered a potential cutaneous r

249 Vemurafenib showed antitumour activity in patients with

250 hibitors, the first-generation RAF inhibitor vemurafenib stimulated in vitro and in vivo growth and i

251 Significantly, vemurafenib stimulation induced FGF2 secretion from kera

252 Finally, vemurafenib strongly induced PXR activity in vitro, but

253 e after failure of the BRAF(V600E) inhibitor vemurafenib, suggesting autophagy inhibition overcame th

254 or and side effects are observed with 480 mg vemurafenib, suggesting that dosing regimens in BRAF-dri

255 ion, imparting resistance to inhibitors like vemurafenib that bind the alphaC "out" conformation.

256 mour, and selective BRAF inhibitors, such as vemurafenib that blocks tumour cell proliferation in pat

257 therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the p

258 veitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneou

259 The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assesse

260 All were successfully managed while vemurafenib therapy was continued.

261 Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients.

262 of acute kidney injury in patients receiving vemurafenib therapy were reported.

263 mice expressing human CYP3A4 did not process vemurafenib to a greater extent than CYP3A4-null animals

264 Our results argue that HPV cooperates with vemurafenib to promote tumorigenesis, in either the pres

265 elerated fibrosarcoma (RAF) kinase inhibitor vemurafenib to treat unresectable melanoma.

266 tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in c

267 sults were validated in vivo in samples from vemurafenib-treated HCL patients within a phase 2 clinic

268 Furthermore, 55% of the cSCCs arising in vemurafenib-treated mice exhibited a wild-type Ras genot

269 inical data are supported by observations in vemurafenib-treated patients with melanoma providing a s

270 Vemurafenib treatment elevated MAPK markers and increase

271 ation of miR-204-5p and miR-211-5p following vemurafenib treatment enables the emergence of resistanc

272 Vemurafenib treatment improved blood counts in all patie

273 For all patients, vemurafenib treatment led to substantial and rapid clini

274 Vemurafenib treatment led to the release of transforming

275 Their expression was rapidly affected by vemurafenib treatment through RNA stabilization.

276 In case 2, after 5 months of vemurafenib treatment, the patient developed a granuloma

277 ever, patients rapidly develop resistance to vemurafenib treatment.

278 (CLL) in the absence of RAS mutations during vemurafenib treatment.

279 erved in a cohort of melanoma patients after vemurafenib treatment.

280 s in liver biochemistries were reported with vemurafenib use in 30% of subjects, 11% developed severe

281 % CI 20.3-not estimable) for cobimetinib and vemurafenib versus 17.4 months (95% CI 15.0-19.8) for pl

282 months (95% CI 9.5-13.4) for cobimetinib and vemurafenib versus 7.2 months (5.6-7.5) for placebo and

283 Although vemurafenib was also highly phototoxic to cultured cells

284 The addition of cobimetinib to vemurafenib was associated with a significant improvemen

285 In the BRIM-3 trial, vemurafenib was associated with risk reduction versus da

286 Vemurafenib was given to eight patients with multisystem

287 A short oral course of vemurafenib was highly effective in patients with relaps

288 TP/RAS ratio in primary CLL cells exposed to vemurafenib was reduced upon SYK inhibition.

289 as well as the effect of rechallenging when vemurafenib was reintroduced.

290 The safety profile for cobimetinib and vemurafenib was tolerable and manageable, and no new saf

291 Vemurafenib was withdrawn after approximately one year o

292 The BRAF inhibitor, vemurafenib, was recently approved for the treatment of

293 ns until 2011, when two drugs-ipilimumab and vemurafenib-were approved following advances in the unde

294 was placed on a clinical trial that combined vemurafenib with a MEK inhibitor, cobimetinib.

295 testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significa

296 e generated A375 melanoma cells resistant to vemurafenib with the goal of investigating changes in mi

297 eneral symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months

298 f 66 patients who had recently progressed on vemurafenib, with a median progression-free survival of

299 es of these PTEN-null melanoma cell lines to vemurafenib, with enhanced cytotoxicity observed followi

300 Vemurafenib (Zelboraf; Genentech, CA) is a highly effect