1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
Abstract Background Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this...
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| Veröffentlicht in: | Annals of oncology 2019-10, Vol.30 (Supplement_5) |
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| creator | Knispel, S Gassenmaier, M Menzies, A M Loquai, C Johnson, D B Franklin, C Gutzmer, R Hassel, J C Weishaupt, C Eigentler, T Schummer, P Kiecker, F Owen, C Schmidgen, M I Kähler, K C Cann, C G Niebel, D Mohr, P Schadendorf, D Zimmer, L |
| description | Abstract
Background
Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown.
Methods
Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined.
Results
404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n = 90, 22%) or ICI (n = 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG ≥1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p = 0.003) or LDH >2x ULN (34% vs 24%, p = 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p ≤ 0.001) and PFS (med 4.7 mo vs 2.3 mo, p |
| doi_str_mv | 10.1093/annonc/mdz255.034 |
| format | Article |
| fullrecord | <record><control><sourceid>oup</sourceid><recordid>TN_cdi_oup_primary_10_1093_annonc_mdz255_034</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/annonc/mdz255.034</oup_id><sourcerecordid>10.1093/annonc/mdz255.034</sourcerecordid><originalsourceid>FETCH-oup_primary_10_1093_annonc_mdz255_0343</originalsourceid><addsrcrecordid>eNqVj0tOwzAURS0EEuGzAGZv2EpNa8dJIeMW1EpIdJC55aYvxJDYkf0CKjtg16SfDTC6Vzpnchh7EHwqeC5n2lpny1m7-0mybMplesEikc3z-Imn4pJFPE9k_JjJ9JrdhPDBOZ_nSR6xXyHTbPPWU-laBFdBp8mgpQDfhmrABr804Q5elysgj8d_JJXxgeLGWATS_h0PgGr0utvDqCjG4DxslrGArQ4DMm3bD2pZY_nZOWMJjK3N1pDzAUbrxXp8x64q3QS8P-8tm7w8F4tV7PpOdd602u-V4OqQq0656pSrhlz5T_0PVMlf4w</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Knispel, S ; Gassenmaier, M ; Menzies, A M ; Loquai, C ; Johnson, D B ; Franklin, C ; Gutzmer, R ; Hassel, J C ; Weishaupt, C ; Eigentler, T ; Schummer, P ; Kiecker, F ; Owen, C ; Schmidgen, M I ; Kähler, K C ; Cann, C G ; Niebel, D ; Mohr, P ; Schadendorf, D ; Zimmer, L</creator><creatorcontrib>Knispel, S ; Gassenmaier, M ; Menzies, A M ; Loquai, C ; Johnson, D B ; Franklin, C ; Gutzmer, R ; Hassel, J C ; Weishaupt, C ; Eigentler, T ; Schummer, P ; Kiecker, F ; Owen, C ; Schmidgen, M I ; Kähler, K C ; Cann, C G ; Niebel, D ; Mohr, P ; Schadendorf, D ; Zimmer, L</creatorcontrib><description>Abstract
Background
Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown.
Methods
Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined.
Results
404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n = 90, 22%) or ICI (n = 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG ≥1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p = 0.003) or LDH >2x ULN (34% vs 24%, p = 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p ≤ 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p = 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented.
Conclusions
In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed.
Editorial acknowledgement
Kai-Martin Thoms, Göttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pföhler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen.
Legal entity responsible for the study
University Clinic Essen, Department of Dermatology.
Funding
Has not received any funding.
Disclosure
S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Novartis; Honoraria (institution): Plexxikon. C. Franklin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. R. Gutzmer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson & Johnson; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall-Hermal; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SUN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: LEO; Advisory / Consultancy: 4SC; Advisory / Consultancy: Incyte; Advisory / Consultancy: Takeda. J.C. Hassel: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pierre Fabre. C. Weishaupt: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Curevac; Honoraria (self): Leo Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Takeda. T. Eigentler: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Leo Pharma; Research grant / Funding (self): Curevac; Research grant / Funding (self): IOVANCE. F. Kiecker: Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. C. Owen: Travel / Accommodation / Expenses: MSD. K.C. Kähler: Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Philogen; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. D. Niebel: Honoraria (self): BMS; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: MSD. P. Mohr: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self): GSK; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self): Merck Serono; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. D. Schadendorf: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Roche; Honoraria (self): MSD; Honoraria (self): Incyte; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self): 4SC; Honoraria (self): AstraZeneca; Honoraria (self), Honoraria (institution), Research grant / Funding (self): BMS; Honoraria (self), Honoraria (institution): Merck-EMD; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Philogen; Honoraria (self): Array. L. Zimmer: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1093/annonc/mdz255.034</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>Annals of oncology, 2019-10, Vol.30 (Supplement_5)</ispartof><rights>European Society for Medical Oncology 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Knispel, S</creatorcontrib><creatorcontrib>Gassenmaier, M</creatorcontrib><creatorcontrib>Menzies, A M</creatorcontrib><creatorcontrib>Loquai, C</creatorcontrib><creatorcontrib>Johnson, D B</creatorcontrib><creatorcontrib>Franklin, C</creatorcontrib><creatorcontrib>Gutzmer, R</creatorcontrib><creatorcontrib>Hassel, J C</creatorcontrib><creatorcontrib>Weishaupt, C</creatorcontrib><creatorcontrib>Eigentler, T</creatorcontrib><creatorcontrib>Schummer, P</creatorcontrib><creatorcontrib>Kiecker, F</creatorcontrib><creatorcontrib>Owen, C</creatorcontrib><creatorcontrib>Schmidgen, M I</creatorcontrib><creatorcontrib>Kähler, K C</creatorcontrib><creatorcontrib>Cann, C G</creatorcontrib><creatorcontrib>Niebel, D</creatorcontrib><creatorcontrib>Mohr, P</creatorcontrib><creatorcontrib>Schadendorf, D</creatorcontrib><creatorcontrib>Zimmer, L</creatorcontrib><title>1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)</title><title>Annals of oncology</title><description>Abstract
Background
Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown.
Methods
Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined.
Results
404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n = 90, 22%) or ICI (n = 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG ≥1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p = 0.003) or LDH >2x ULN (34% vs 24%, p = 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p ≤ 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p = 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented.
Conclusions
In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed.
Editorial acknowledgement
Kai-Martin Thoms, Göttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pföhler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen.
Legal entity responsible for the study
University Clinic Essen, Department of Dermatology.
Funding
Has not received any funding.
Disclosure
S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Novartis; Honoraria (institution): Plexxikon. C. Franklin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. R. Gutzmer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson & Johnson; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall-Hermal; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SUN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: LEO; Advisory / Consultancy: 4SC; Advisory / Consultancy: Incyte; Advisory / Consultancy: Takeda. J.C. Hassel: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pierre Fabre. C. Weishaupt: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Curevac; Honoraria (self): Leo Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Takeda. T. Eigentler: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Leo Pharma; Research grant / Funding (self): Curevac; Research grant / Funding (self): IOVANCE. F. Kiecker: Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. C. Owen: Travel / Accommodation / Expenses: MSD. K.C. Kähler: Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Philogen; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. D. Niebel: Honoraria (self): BMS; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: MSD. P. Mohr: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self): GSK; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self): Merck Serono; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. D. Schadendorf: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Roche; Honoraria (self): MSD; Honoraria (self): Incyte; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self): 4SC; Honoraria (self): AstraZeneca; Honoraria (self), Honoraria (institution), Research grant / Funding (self): BMS; Honoraria (self), Honoraria (institution): Merck-EMD; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Philogen; Honoraria (self): Array. L. Zimmer: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.</description><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqVj0tOwzAURS0EEuGzAGZv2EpNa8dJIeMW1EpIdJC55aYvxJDYkf0CKjtg16SfDTC6Vzpnchh7EHwqeC5n2lpny1m7-0mybMplesEikc3z-Imn4pJFPE9k_JjJ9JrdhPDBOZ_nSR6xXyHTbPPWU-laBFdBp8mgpQDfhmrABr804Q5elysgj8d_JJXxgeLGWATS_h0PgGr0utvDqCjG4DxslrGArQ4DMm3bD2pZY_nZOWMJjK3N1pDzAUbrxXp8x64q3QS8P-8tm7w8F4tV7PpOdd602u-V4OqQq0656pSrhlz5T_0PVMlf4w</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Knispel, S</creator><creator>Gassenmaier, M</creator><creator>Menzies, A M</creator><creator>Loquai, C</creator><creator>Johnson, D B</creator><creator>Franklin, C</creator><creator>Gutzmer, R</creator><creator>Hassel, J C</creator><creator>Weishaupt, C</creator><creator>Eigentler, T</creator><creator>Schummer, P</creator><creator>Kiecker, F</creator><creator>Owen, C</creator><creator>Schmidgen, M I</creator><creator>Kähler, K C</creator><creator>Cann, C G</creator><creator>Niebel, D</creator><creator>Mohr, P</creator><creator>Schadendorf, D</creator><creator>Zimmer, L</creator><general>Oxford University Press</general><scope/></search><sort><creationdate>20191001</creationdate><title>1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)</title><author>Knispel, S ; Gassenmaier, M ; Menzies, A M ; Loquai, C ; Johnson, D B ; Franklin, C ; Gutzmer, R ; Hassel, J C ; Weishaupt, C ; Eigentler, T ; Schummer, P ; Kiecker, F ; Owen, C ; Schmidgen, M I ; Kähler, K C ; Cann, C G ; Niebel, D ; Mohr, P ; Schadendorf, D ; Zimmer, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-oup_primary_10_1093_annonc_mdz255_0343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Knispel, S</creatorcontrib><creatorcontrib>Gassenmaier, M</creatorcontrib><creatorcontrib>Menzies, A M</creatorcontrib><creatorcontrib>Loquai, C</creatorcontrib><creatorcontrib>Johnson, D B</creatorcontrib><creatorcontrib>Franklin, C</creatorcontrib><creatorcontrib>Gutzmer, R</creatorcontrib><creatorcontrib>Hassel, J C</creatorcontrib><creatorcontrib>Weishaupt, C</creatorcontrib><creatorcontrib>Eigentler, T</creatorcontrib><creatorcontrib>Schummer, P</creatorcontrib><creatorcontrib>Kiecker, F</creatorcontrib><creatorcontrib>Owen, C</creatorcontrib><creatorcontrib>Schmidgen, M I</creatorcontrib><creatorcontrib>Kähler, K C</creatorcontrib><creatorcontrib>Cann, C G</creatorcontrib><creatorcontrib>Niebel, D</creatorcontrib><creatorcontrib>Mohr, P</creatorcontrib><creatorcontrib>Schadendorf, D</creatorcontrib><creatorcontrib>Zimmer, L</creatorcontrib><jtitle>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knispel, S</au><au>Gassenmaier, M</au><au>Menzies, A M</au><au>Loquai, C</au><au>Johnson, D B</au><au>Franklin, C</au><au>Gutzmer, R</au><au>Hassel, J C</au><au>Weishaupt, C</au><au>Eigentler, T</au><au>Schummer, P</au><au>Kiecker, F</au><au>Owen, C</au><au>Schmidgen, M I</au><au>Kähler, K C</au><au>Cann, C G</au><au>Niebel, D</au><au>Mohr, P</au><au>Schadendorf, D</au><au>Zimmer, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)</atitle><jtitle>Annals of oncology</jtitle><date>2019-10-01</date><risdate>2019</risdate><volume>30</volume><issue>Supplement_5</issue><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Abstract
Background
Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown.
Methods
Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined.
Results
404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n = 90, 22%) or ICI (n = 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG ≥1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p = 0.003) or LDH >2x ULN (34% vs 24%, p = 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p ≤ 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p = 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented.
Conclusions
In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed.
Editorial acknowledgement
Kai-Martin Thoms, Göttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pföhler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen.
Legal entity responsible for the study
University Clinic Essen, Department of Dermatology.
Funding
Has not received any funding.
Disclosure
S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution): Amgen; Honoraria (institution): Novartis; Honoraria (institution): Plexxikon. C. Franklin: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. R. Gutzmer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson & Johnson; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall-Hermal; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SUN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy: LEO; Advisory / Consultancy: 4SC; Advisory / Consultancy: Incyte; Advisory / Consultancy: Takeda. J.C. Hassel: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pierre Fabre. C. Weishaupt: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Curevac; Honoraria (self): Leo Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Takeda. T. Eigentler: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Leo Pharma; Research grant / Funding (self): Curevac; Research grant / Funding (self): IOVANCE. F. Kiecker: Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. C. Owen: Travel / Accommodation / Expenses: MSD. K.C. Kähler: Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): BMS; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Philogen; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. D. Niebel: Honoraria (self): BMS; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: MSD. P. Mohr: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self): GSK; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self): Merck Serono; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. D. Schadendorf: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Amgen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Roche; Honoraria (self): MSD; Honoraria (self): Incyte; Honoraria (self), Honoraria (institution): Regeneron; Honoraria (self): 4SC; Honoraria (self): AstraZeneca; Honoraria (self), Honoraria (institution), Research grant / Funding (self): BMS; Honoraria (self), Honoraria (institution): Merck-EMD; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Philogen; Honoraria (self): Array. L. Zimmer: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.</abstract><pub>Oxford University Press</pub><doi>10.1093/annonc/mdz255.034</doi></addata></record> |
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| ispartof | Annals of oncology, 2019-10, Vol.30 (Supplement_5) |
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| language | eng |
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| source | EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| title | 1345POutcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI) |
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