ライフサイエンスコーパス: osimertinib

1 tic strategy to overcome tumor resistance to osimertinib.

2 stance mutations and synergize with the drug osimertinib.

3 irst and third generation TKIs erlotinib and osimertinib.

4 limited options after disease progression on osimertinib.

5 ) were enrolled and initiated tepotinib plus osimertinib.

6 chanisms accounting for apoptosis induced by osimertinib.

7 tive of a safety issue in patients receiving osimertinib.

8 ive dramatic clinical benefit from sequenced osimertinib.

9 >=2.3), following progression on first-line osimertinib.

10 ere reported as being related to Teliso-V or osimertinib.

11 tabolic (18)F-FDG PET response and continued osimertinib.

12 both resistant LUAD cells and stem cells to Osimertinib.

13 h CDCP1 and AXL increased the sensitivity to osimertinib.

14 GFR T790M-positive clone impacts response to osimertinib.

15 in patients with NSCLC after progression on osimertinib.

16 ncluding erlotinib, gefitinib, afatinib, and osimertinib.

17 from patients with lung cancer treated with osimertinib.

18 benefit from sequenced targeted therapy with osimertinib.

19 ircFBXW7 determined the cellular response to Osimertinib.

20 unction in mediating therapeutic efficacy of osimertinib.

21 s whose disease progresses during front-line osimertinib.

22 FAK signaling induced by the EGFR inhibitor osimertinib.

23 istant mutations that confer a resistance to osimertinib.

24 sistance and resensitized resistant cells to osimertinib.

25 d in all patients receiving savolitinib plus osimertinib.

26 ing observed at an increased frequency after osimertinib.

27 oved targeted therapies after progression on osimertinib.

28 ed tyrosine kinase inhibitors, nilotinib and osimertinib.

29 y or the AKT pathway enhanced the effects of osimertinib.

30 e mechanisms developed in patients receiving osimertinib.

31 om all patients in the first-in-man study of osimertinib.

32 of outcome from a third-generation EGFR-TKI, osimertinib.

33 or assessed as possibly treatment-related to osimertinib.

34 of 28, 68%) and within 12 months of stopping osimertinib (11 of 19, 58%).

35 diotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients).

36 zertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.

37 Among 262 patients receiving first-line osimertinib, 53% developed CNS metastases (36% de novo,

38 Overall, 216 patients were randomised (143 osimertinib, 73 placebo).

39 In part B, patients received oral osimertinib 80 mg and savolitinib 600 mg daily; after a

40 ) a pooled data set of patients treated with osimertinib 80 mg from across the clinical trial program

41 ) or once daily (o.d.), or 600 mg o.d.] plus osimertinib 80 mg o.d., or savolitinib 300 mg b.i.d. plu

42 nts received oral tepotinib 500 mg plus oral osimertinib 80 mg once daily.

43 Patients received osimertinib 80 mg orally once daily for up to two 28-day

44 R tyrosine-kinase inhibitor therapy received osimertinib 80 mg orally once daily; treatment could con

45 Thr790Met negative; these patients received osimertinib 80 mg plus savolitinib 300 mg.

46 m-based CRT were randomised 2 : 1 to receive osimertinib (80 mg daily) or placebo until progression [

47 overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95%

48 Osimertinib, a mutant-specific third-generation EGFR tyr

49 eceptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI).

50 manage the inevitable acquired resistance to osimertinib, a third-generation EGFR inhibitor for the t

51 GFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous

52 olitinib), a potent, selective MET TKI, plus osimertinib, a third-generation EGFR TKI, have provided

53 Osimertinib, a third-generation EGFR-TKI, has nowadays b

54 Osimertinib-a third-generation epidermal growth factor r

55 inical validation of this strategy to manage osimertinib acquired resistance.

56 gnificantly higher in the group treated with osimertinib (adjusted subdistribution HR, 4.00; 95% CI,

57 better than the third-generation inhibitor, osimertinib, against EGFR and HER2 exon 20 insertion mut

58 Osimertinib alone but likely to benefit from Osimertinib/AKT blockade combination treatments.

59 ents who are at risk of responding poorly to Osimertinib alone but likely to benefit from Osimertinib

60 ib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naive EGFR-mutant

61 atients who may benefit from longer adjuvant osimertinib, although this requires clinical confirmatio

62 zertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus

63 Osimertinib, an epidermal growth factor receptor tyrosin

64 ith EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosin

65 with either osimertinib or a combination of osimertinib and a SOS1 inhibitor, with the combination p

66 do not suggest a causal relationship between osimertinib and cardiac failure.

67 and 31 (23.5%) patients received subsequent osimertinib and chemotherapy, respectively.

68 h to identify an optimal dosing schedule for osimertinib and dacomitinib combination therapy.

69 A combination of osimertinib and dacomitinib could therefore induce more

70 indicate a relationship between exposure to osimertinib and decreases in LVEF from baseline.

71 l patients who received at least one dose of osimertinib and had measurable disease at baseline accor

72 f the highly effective third-generation TKIs osimertinib and lorlatinib, respectively.

73 ) in patients with progression on first-line osimertinib and MET IHC3+/>=90% and/or FISH10+ status re

74 Following osimertinib and NPV treatment, loss of the ex19del mutat

75 rategy for overcoming acquired resistance to osimertinib and other 3rd generation EGFR-TKIs by target

76 In this study, we found that osimertinib and other EGFR-TKIs increased the expression

77 -mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randoml

78 Osimertinib and rociletinib are third-generation irrever

79 The combination of osimertinib and savolitinib has acceptable risk-benefit

80 ich were overcome by combined treatment with osimertinib and SFK inhibitors.

81 ct for poor outcome in patients treated with osimertinib and sotorasib.

82 have demonstrated a novel connection between osimertinib and SREBP1 degradation and its impact on the

83 n the response of EGFR mutant NSCLC cells to osimertinib and suggested an effective strategy for over

84 a novel mechanism of acquired resistance to osimertinib and the reversal of which could improve the

85 (1.6 mg/kg, n = 20; 1.9 mg/kg, n = 18) plus osimertinib and were included in this analysis.

86 ation (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib).

87 esensitized drug-tolerant persister cells to osimertinib, and knockout or inhibition of SOS1 reduced

88 rategy for overcoming acquired resistance to osimertinib, and possibly other EGFR inhibitors, via tar

89 FR tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR

90 ccess of the third-generation EGFR inhibitor osimertinib as a first-line treatment of EGFR-mutant non

91 tamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated adva

92 brain-penetrating EGFR inhibitors identified osimertinib as the most potent inhibitor of the EGFR-TAZ

93 hypoxia promotes resistance to the EGFR TKI osimertinib (AZD9291) in the non-small cell lung cancer

94 Osimertinib (AZD9291) is an oral, potent, irreversible E

95 Emergence of acquired resistance to osimertinib (AZD9291), the first-approved third-generati

96 NA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo.

97 e cardiac failure risk in patients receiving osimertinib by evaluating the available data.

98 f EGFR-TKIs (gefitinib, erlotinib, afatinib, osimertinib) by data mining using the FDA adverse event

99 better understand the mechanisms underlying osimertinib cardiotoxicity and explore cardioprotective

100 sarcomere disarray as the main mechanism of osimertinib cardiotoxicity.

101 amtiv is shown to be effective in preventing osimertinib cardiotoxicity.

102 Despite the intracranial efficacy of osimertinib, central nervous system (CNS) metastases rem

103 5%) patients; most events occurred following osimertinib cessation (19 of 28, 68%) and within 12 mont

104 Consequently, osimertinib combined with the telomere inhibitor, 6-Thio

105 get resistance to third-generation inhibitor osimertinib, commonly develops through C797S mutation th

106 shows superior efficacy in combination with osimertinib compared to the single agents.

107 s further identified as a putative target of osimertinib, connecting its decreased phosphorylation to

108 ted progression-free survival durations with osimertinib consolidation.

109 Therefore, osimertinib could be a suitable treatment for patients w

110 Mechanistically, osimertinib decreased Topo IIalpha levels in EGFRm NSCLC

111 Osimertinib demonstrated clinically meaningful improveme

112 In LAURA (NCT03521154), osimertinib demonstrated statistically significant impro

113 However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical

114 d resolved without treatment of the event or osimertinib discontinuation.

115 Despite widespread osimertinib distribution in vivo, the brain microvascula

116 essed in all patients receiving at least one osimertinib dose (full analysis set).

117 gnaling intermediate SOS1 promoted continued osimertinib efficacy in sensitive cells and restored sen

118 Osimertinib facilitated degradation of the mature form o

119 s were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resecti

120 Adjuvant osimertinib for patients with EGFR-mutant tumors, preope

121 lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 ve

122 amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.

123 In the osimertinib group, DFS or MRD events were detected in 28

124 nd in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed respo

125 The third-generation of EGFR-TKI osimertinib has been approved as a first-line therapy in

126 primary end point has already been reported.Osimertinib has been established as a standard of care f

127 Since its approval in April 2018, osimertinib has been widely adopted as first-line therap

128 hanisms, including resistance mechanisms, of osimertinib has led to the identification of a novel and

129 t-generation inhibitor gefitinib followed by osimertinib) has not been formally compared.

130 As the third generation EGFR TKI, osimertinib, has now been adopted in the first-line sett

131 n as a mechanism of resistance to first-line osimertinib have few treatment options.

132 EGFR mutations or acquired CNS metastases on osimertinib have worse outcomes.

133 n of several covalent drugs (e.g., afatinib, osimertinib, ibrutinib, neratinib, and CC-292).

134 In the Phase III FLAURA study, first-line osimertinib improved outcomes vs comparator EGFR-TKIs in

135 and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-deri

136 mpact of tumour heterogeneity on response to osimertinib in advanced stage NSCLC patients and could h

137 sine kinase inhibitors such as Erlotinib and Osimertinib in certain tumors with mesenchymal-like feat

138 ht dictate future development strategies for osimertinib in clinical trials.

139 and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer.

140 ulture and increased the antitumor effect of osimertinib in mice.

141 We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non

142 onged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor rec

143 a phase I/Ib trial evaluating Teliso-V plus osimertinib in patients with NSCLC after progression on

144 azertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1

145 Per protocol, 73% of patients switched to osimertinib in the sequential arm.

146 ighly selective MET inhibitor, combined with osimertinib in this population.

147 We modeled acquired resistance to osimertinib in transgenic mouse models of EGFR(L858R) -i

148 which we demonstrate to confer resistance to osimertinib in vitro that can be partially reversed by P

149 tamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a

150 hibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non-small cell lung cancer (NSCLC) is li

151 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM

152 identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude d

153 Furthermore, osimertinib increased membrane-bound TRAIL and DR5 membr

154 o this, we uncovered here that gefitinib and osimertinib increased STAT3 phosphorylation (p-STAT3) in

155 Moreover, osimertinib increased STAT3-dependent transcription of T

156 vered connection between TRAIL induction and osimertinib-induced apoptosis in EGFRm NSCLC cells, incr

157 cell lines restored their susceptibility to osimertinib-induced DNA damage and apoptosis.

158 Hence, osimertinib induces IL6/STAT3-mediated TRAIL expression

159 Osimertinib is a recommended treatment for advanced non-

160 Osimertinib is a third-generation EGFR-tyrosine kinase i

161 Osimertinib is a third-generation tyrosine kinase inhibi

162 The compound osimertinib is a third-generation tyrosine kinase inhibi

163 Osimertinib is a third-generation, CNS-active, irreversi

164 Osimertinib is approved for the treatment of non-small-c

165 tors (EGFR TKIs), it remains unclear whether osimertinib is associated with more cancer therapy-relat

166 inase inhibitor therapy, and T790M mutation, osimertinib is recommended; if NSCLC lacks the T790M mut

167 Osimertinib is the current standard of care for patients

168 mutant non-small cell lung cancer (NSCLC) to osimertinib is the foundation for development of mechani

169 Osimertinib is the mainstay of therapy for patients with

170 vised recommendations include the following: Osimertinib is the optimal first-line treatment for pati

171 Osimertinib is the standard first-line treatment for adv

172 ile third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resi

173 Although it has been reported that osimertinib mesylate provides better survival benefits c

174 d levels of mSREBP1, which were resistant to osimertinib modulation.

175 ib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or dis

176 nstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progress

177 79; comparator EGFR-TKI, n = 277) and AURA3 (osimertinib, n = 279; chemotherapy, n = 140), and (2) a

178 advanced non-small-cell lung cancer, FLAURA (osimertinib, n = 279; comparator EGFR-TKI, n = 277) and

179 6 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316).

180 KI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2).

181 adenocarcinomas (LUADs), including 93 paired osimertinib-naive and -resistant EGFR-mutant tumors.

182 EC-dominant mutational signature compared to osimertinib-naive samples (28% versus 14%, P = 0.03).

183 before vaccination and its expansion during osimertinib/NPV therapy.

184 d nearly completely when treated with either osimertinib or a combination of osimertinib and a SOS1 i

185 erapy such as the tyrosine kinase inhibitors osimertinib or lorlatinib, respectively.

186 fied in patients with disease progression on osimertinib or lorlatinib.

187 trategies to overcome acquired resistance to osimertinib or other third-generation EGFR inhibitors.

188 during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurre

189 on or gene knockout abrogated the ability of osimertinib or recombinant human IL6 to elevate TRAIL le

190 Teliso-V (intravenously, every 2 weeks) plus osimertinib (orally, 80 mg once daily).

191 pairing YAP activation, ultimately improving osimertinib (Osi) sensitivity in LUAD cells.

192 mall cell lung cancers (NSCLCs) treated with osimertinib (OSI), and the mechanisms are not well defin

193 Patients took 20-240 mg osimertinib per day until disease progression or develop

194 Combination first-line osimertinib plus erlotinib treatment prevented the emerg

195 Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or os

196 Osimertinib plus platinum-pemetrexed demonstrated improv

197 In part D, 42 patients received osimertinib plus savolitinib 300 mg.

198 In part B, 138 patients received osimertinib plus savolitinib 600 mg (n=130) or 300 mg (n

199 Here, we report the assessment of osimertinib plus savolitinib in two global expansion coh

200 CNS PFS and TTDM versus placebo, supporting osimertinib post-CRT as the standard of care in unresect

201 naive NSCLC cells, SOS1 inhibition enhanced osimertinib potency by limiting the reactivation of RTK-

202 red as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferatio

203 ity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor rec

204 ed osimertinib-resistant cells and tumors to osimertinib primarily through enhancing Bim-dependent in

205 tus receiving savolitinib 300 mg b.i.d. plus osimertinib (primary efficacy population).

206 -of-care third-generation covalent inhibitor osimertinib, primary or acquired resistance to these age

207 ach to the evaluation and management of post-osimertinib progression as well as a compendium of activ

208 Median overall survival after osimertinib progression was 5.4 months (95% CI 4.1-10.0)

209 analysis showed that the CSF to free plasma osimertinib ratio was 22%.

210 ; no targeted treatments are approved in the osimertinib-relapsed setting.

211 esults show that the therapeutic efficacy of osimertinib relies on effective TAZ inhibition, thus ide

212 further limited the development of acquired osimertinib resistance and resensitized resistant cells

213 agonist of ERRalpha, overcome gefitinib and osimertinib resistance both in vitro and in vivo.

214 Importantly, osimertinib resistance caused by epithelial-mesenchymal

215 o the biological and molecular properties of osimertinib resistance EGFR mutations and evaluates ther

216 ST1 overexpression resulted in erlotinib and osimertinib resistance in EGFR-mutant NSCLC cells.

217 nd suggest strategies to overcome or prevent osimertinib resistance in vivo.

218 Understanding osimertinib resistance mechanisms and currently availabl

219 However, the rapid development of osimertinib resistance renders the unsustainable treatme

220 hed and mechanistic studies of CAGE-mediated osimertinib resistance were performed.

221 ort tumor cell survival and the emergence of osimertinib resistance.

222 eveloping anticancer drugs that can overcome osimertinib resistance.

223 Using data compiled from 6 osimertinib-resistance series, we describe here the hete

224 Cells that were osimertinib resistant and had MET amplification or showe

225 inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant.

226 ere is no drug specifically approved for the osimertinib-resistant BMs of NSCLC yet.

227 ystem was designed for specifically treating osimertinib-resistant BMs.

228 erlotinib and afatinib caused regression of osimertinib-resistant C797S-containing tumors, whereas o

229 xpression promotes survival of gefitinib and osimertinib-resistant cancer cells.

230 igh brain penetration and potent activity in osimertinib-resistant cell lines bearing L858R/C797S and

231 o osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their suscepti

232 on of DNA damage; these effects were lost in osimertinib-resistant cell lines that possess elevated l

233 overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX)

234 asing the survival and inducing apoptosis of osimertinib-resistant cells and in suppressing the growt

235 rmacological inhibition of SREBP1 sensitized osimertinib-resistant cells and tumors to osimertinib pr

236 DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q

237 SFK family member YES1 was amplified in osimertinib-resistant EGFR-mutant tumor cells, the effec

238 ch are poised to proliferate in the brain as osimertinib-resistant lesions over time.

239 In osimertinib-resistant lung cancer cell lines harboring T

240 Osimertinib-resistant non-small cell lung cancer cells (

241 In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent a

242 In EGFR-mutant lung cancers, osimertinib-resistant samples more frequently displayed

243 Specifically, mutations detected in osimertinib-resistant tumors but not in pre-treatment sa

244 I trial, effectively inhibited the growth of osimertinib-resistant tumors, regressed EGFRm NSCLC pati

245 stant cells and in suppressing the growth of osimertinib-resistant tumors.

246 atment of Notch inhibitors with gefitinib or osimertinib, respectively.

247 Osimertinib resulted in a significant progression-free s

248 ensitive EGFR-mutant NSCLC cells compromised osimertinib's cell-killing effects.

249 essibility and gene regulatory signatures of osimertinib sensitive and resistant EGFR-mutant cell and

250 ignaling under continuous EGFR inhibition in osimertinib-sensitive cells.

251 identifying TAZ as a potential biomarker of osimertinib sensitivity.

252 arcinoma patients treated with gefitinib and osimertinib show a therapeutic benefit limited by the ap

253 Osimertinib showed clinical activity with manageable sid

254 Ramucirumab plus osimertinib significantly prolonged PFS compared with os

255 itive for T790M in plasma have outcomes with osimertinib that are equivalent to patients positive by

256 ts in different acquired EGFR mutations than osimertinib that mediate on-target resistance.

257 en combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-1

258 At 24 months after osimertinib, the DFS and MRD event-free rate was 66%.

259 s of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI

260 estigation of combining SOS1 inhibitors with osimertinib to achieve more durable responses and suppre

261 cancer treated with the third-generation TKI osimertinib to investigate mechanisms of persistence at

262 antly compromised the cell-killing effect of osimertinib, together suggesting a DR5-dependent effect.

263 ASCL1 overexpression increased osimertinib tolerance in vitro as well, apparently indep

264 tment to chemotherapy in lung adenocarcinoma osimertinib-treated patients after disease progression.

265 maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up, with

266 nderstanding of DTP heterogeneity seen after osimertinib treatment and provide insights into potentia

267 patients were screened, of whom 210 started osimertinib treatment between June 13, 2014, and Oct 27,

268 In one of the PDXs analyzed, osimertinib treatment caused dramatic transcriptomic cha

269 with most MRD or DFS events occurring after osimertinib treatment discontinuation or completion.

270 EGFR-dependent and independent mechanisms of osimertinib treatment failure.

271 MET-based resistance following osimertinib treatment for epidermal growth factor recept

272 ation in the EGFR kinase domain has hampered Osimertinib treatment in patients with advanced EGFR-mut

273 ncomitant Notch inhibition with gefitinib or osimertinib treatment induced a p-STAT3-dependent strong

274 Osimertinib treatment leads to significant contractile d

275 ints to an absolute value of < 50% following osimertinib treatment were observed in 8 (3.1%) and 14 (

276 ints to an absolute value of < 50% following osimertinib treatment were observed in 8 (3.1%) and 14 (

277 Conclusion: Connecting theranostic osimertinib treatment with early metabolic response asse

278 mutations, private mutations acquired after osimertinib treatment, and areas of large-scale genomic

279 in patients with cardiac risk factors before osimertinib treatment, cardiac monitoring, including an

280 an assessment of LVEF at baseline and during osimertinib treatment, is advised.

281 rises in approximately 33% of patients after osimertinib treatment, occurs in <3% after rociletinib.

282 the outgrowth of disseminated tumor cells on osimertinib treatment, preferentially in response to ext

283 me patients may benefit from longer adjuvant osimertinib treatment.

284 to tyrosine kinase inhibitors (TKI), such as osimertinib used to treat EGFR-mutant lung adenocarcinom

285 e interval (CI) not calculable (NC)-NC] with osimertinib versus 14.9 months (95% CI 7.4 months-NC) wi

286 ogression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazar

287 onths was 86% versus 36% for patients in the osimertinib versus placebo groups (hazard ratio, 0.23 (9

288 e-sensitizes a subset of resistant models to osimertinib via inhibition of mSWI/SNF-mediated regulati

289 stance to third-generation EGFR TKIs such as osimertinib via the EGFR(C797S) mutation remains a highl

290 ayed the emergence of acquired resistance to osimertinib, warranting clinical validation of this stra

291 icenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutat

292 rt study of patients with EGFR-mutant NSCLC, osimertinib was associated with a higher incidence of CT

293 Occurrence of CTRCEs in patients receiving osimertinib was significantly higher compared with patie

294 tween APOBEC and mechanisms of resistance to osimertinib were investigated.

295 69.2 [11.3] years), 195 (48.6%) treated with osimertinib were matched with 206 (51.4%) treated with o

296 etastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivant

297 ve EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-r

298 Interestingly, the triple-combination of osimertinib with Mcl-1 inhibition and Bax activation exh

299 of CDCP1 or AXL restored the sensitivity to osimertinib with reduced activation of SRC and AKT.

300 ients treated, 341 received savolitinib plus osimertinib, with 80 of these included in the primary ef