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Found 2 Presentations For Request "Abs: 538P"
538P - Vemurafenib in non-melanoma V600 and non-V600 BRAF mutated cancers: Results of the AcSé basket trial
- Pascale Tomasini (Marseille, France)
Abstract
Background
BRAF mutations are observed in several cancer histotypes at low frequency (<5%). Vemurafenib is active in BRAF-V600-mutated melanoma. Non-melanoma BRAF-V600-mutated cancers were also reported to respond to BRAF inhibitors. The ACSE program launched by the French National Cancer Institute (INCa) aimed to provide controlled access to targeted therapies outside their label. Here we report the final analysis of efficacy endpoint of the ACSE Vemurafenib study (cf ESMO2016, #55PD).
Methods
BRAF mutational status (exons 11 and 15) was assessed by direct sequencing or NGS within the INCa molecular genetic platforms network. Patients with various BRAF (V600 or non V600) mutated cancers (e.g., lung, ovarian, bladder, thyroid, prostate cancers, cholangiocarcinoma, sarcoma/GIST, multiple myeloma, chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL)) and progressing after ≥1 standard treatment, were included in dedicated cohorts to receive vemurafenib 960 mg BID. A Bayesian approach allowed sequential analyses in each cohort and early stopping using an inefficacy boundary for objective response rate (ORR) of 10%. ORR was assessed every 8 weeks using RECIST v1.1 criteria for solid tumors and specific criteria for myeloma, CLL and HCL.
Results
From Oct. 2014 to May. 2019, 216 out of 2500+ screened patients were included at 116 centers. Median age was 66 years [18-85], 51% were males. (a) Minimum follow-up of 16 weeks. (b) 2 histiocytosis and 1 glioma. (c) 2 histiocytosis, 3 ganglioglioma, 2 xantho astrocytoma, 2 glioblastoma, 1 appendix, 1 unknown primary.
Included N=216 Median duration of treatment (months) Analyzed for response(a) N=212 Best overall response Bayesian estimation of mean ORR CR PR SD PD NE V600 mutated NSCLC 101 3.4 100 43 22 15 20 45% cholangiocarcinoma 9 5.5 9 1 6 2 1/9 Thyroid 6 1.8 6 4 2 0/6 Ovary 6 5.2 6 3 2 1 3/6 Sarcoma 3 23 3 1 1 1 2/3 Bladder 2 0.9 2 1 1 0/2 Multiple myeloma 2 5.5 2 1 1 1/2 HCL 27 2.2 27 13 12 2 90% Miscellaneous: V600 mutated Non-V600 mutated 33 27 5.7 1.6 32 25 3(b) 0 11(c) 1 5 4 6 14 7 6 14/32 1/25
Conclusions
Antitumor activity of vemurafenib was important in V600-mutated NSCLC, HCL, sarcoma, ovarian cancer, brain tumors, histiocytosis and gangliogliomas. Importantly, Non-V600 mutated tumors derived no benefit.
Clinical trial identification
NCT02304809.
Legal entity responsible for the study
UNICANCER.
Funding
Foundation ARC; Institut National du Cancer; UNICANCER; Roche.
Disclosure
P. Tomasini: Research grant/Funding (institution), Non-remunerated activity/ies: Roche; Research grant/Funding (institution), Non-remunerated activity/ies: AZ; Research grant/Funding (institution), Non-remunerated activity/ies: BI; Research grant/Funding (institution), Non-remunerated activity/ies: BMS; Research grant/Funding (institution), Non-remunerated activity/ies: Takeda; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZenca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengruii; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda. D. Malka: Leadership role: Member of the steering committee of The Prodige intergroup; Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self): MSD; Honoraria (self): Merck Serono; Honoraria (self): Servier; Honoraria (self): Agios; Honoraria (self): Incyte; Honoraria (self): Novartis; Honoraria (self): SANOFI; Honoraria (self): Roche; Honoraria (self): Haliodx; Honoraria (self): Pierre Fabre Oncology. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZenca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Roche/Genentech; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sereno; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Non-remunerated activity/ies: Gineco; Non-remunerated activity/ies: ENGOT; Non-remunerated activity/ies: GCIG; Non-remunerated activity/ies: European Community; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: ESGO; Non-remunerated activity/ies: IGSC; Non-remunerated activity/ies: Inca ; Non-remunerated activity/ies: Swiss, Italian, Belgium and German health authorities.. J-Y. Blay: Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution): Roche; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution): Novartis ; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution): GSK. All other authors have declared no conflicts of interest.
1165P - Subgroup analysis by Ki-67 and primary tumour origins of the randomized, placebo-controlled phase III study of surufatinib in advanced well-differentiated extrapancreatic neuroendocrine tumours (SANET-ep)
- Zhiwei Zhou (Guangzhou, China)
Abstract
Background
Surufatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (1,2,3), fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, has demonstrated superior efficacy in extrapancreatic neuroendocrine tumors (NETs) in a phase III study (SANET-ep, ESMO 2019 Abs. LBA76). The proliferation marker Ki-67 and primary tumor origins are the major prognostic factors in NETs.
Methods
The post-hoc efficacy analysis of surufatinib versus placebo was conducted by Ki-67 subcategory (<3%, 3-10%, >10%) and primary tumor origins (foregut, midgut, hindgut, others or unknown) in patients (pts) with advanced well-differentiated (grade 1 or 2) extrapancreatic NETs. The primary endpoint (progression-free survival [PFS]) and secondary endpoint (objective response rate [ORR]) both by investigator assessment (RECIST1.1) were analyzed.
Results
Median PFS was significantly prolonged with surufatinib compared to placebo in subgroups of Ki-67 3-10% (7.6 vs 4.6 months [mo], hazard ratio [HR] 0.47,
Conclusions
Surufatinib demonstrated clinically significant benefits for pts with advanced well-differentiated extrapancreatic NETs compared to placebo. Results of this exploratory analysis were consistent with those reported for the SANET-ep primary analysis, and improved outcomes were observed across major subgroups.
Clinical trial identification
NCT02588170.
Legal entity responsible for the study
Hutchison MediPharma Limited.
Funding
Hutchison MediPharma Limited.
Disclosure
J. Li, J. He: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.