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
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract