Abstract 2050
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.
Clinical trial identification
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.
Resources from the same session
5529 - Safety and efficacy of Ac-225-PSMA-617 in metastatic castration resistant prostate cancer (mCRPC) after failure of Lu-177-PSMA
Presenter: Robert Tauber
Session: Poster Display session 3
Resources:
Abstract
3611 - Phase II trial of SM 88 in Non-Metastatic Biochemical Recurrent Prostate Cancer.
Presenter: Benjamin Gartrell
Session: Poster Display session 3
Resources:
Abstract
2492 - A phase 1 study of Ad5 PSA/MUC-1/Brachyury Vaccine in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)
Presenter: Marijo Bilusic
Session: Poster Display session 3
Resources:
Abstract
3142 - Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand Binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer
Presenter: Douglas McNeel
Session: Poster Display session 3
Resources:
Abstract
4327 - Impact of germline mutations in Homologous Recombination (HR) genes on the response to Radium-223 for metastatic castration resistant prostate cancer (mCRPC)
Presenter: Elena Castro
Session: Poster Display session 3
Resources:
Abstract
3600 - Serum biomarkers of bone metabolism in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with Radium-223 (Ra223): Results from a prospective multicentre study
Presenter: Nuria Romero Laorden
Session: Poster Display session 3
Resources:
Abstract
3742 - Prognostic value of tumor suppression genes (TP53, PTEN, Rb) in metastatic hormone sensitive prostate cancer
Presenter: Miguel Gonzalez Velez
Session: Poster Display session 3
Resources:
Abstract
2643 - Germline sequencing of advanced prostate cancer patients in the BARCODE2 trial
Presenter: Sarah Benafif
Session: Poster Display session 3
Resources:
Abstract
4349 - Impact of treatment sequence in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): data from the prospective PROREPAIR-B study.
Presenter: Carlo Cattrini
Session: Poster Display session 3
Resources:
Abstract
3301 - Implications of Single Nucleotide Polymorphisms (SNPs) in Androgen Related-Genes in Outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (Abi) and Enzalutamide (Enza)
Presenter: Isabel Aragon
Session: Poster Display session 3
Resources:
Abstract