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E-Poster Display

1102P - Clinical benefit in BRAFV600 mutation-positive melanoma defined by programmed death ligand 1 (PD-L1) and/or lactate dehydrogenase (LDH) status: Exploratory analyses from the IMspire150 study

Date

17 Sep 2020

Session

E-Poster Display

Topics

Targeted Therapy

Tumour Site

Melanoma

Presenters

Paolo Ascierto

Citation

Annals of Oncology (2020) 31 (suppl_4): S672-S710. 10.1016/annonc/annonc280

Authors

P.A. Ascierto1, C. Robert2, K. Lewis3, R. Gutzmer4, D. Stroyakovskiy5, H.J. Gogas6, S. Protsenko7, R.P. Pereira8, T. Eigentler9, P. Rutkowski10, L. Demidov11, G. Moiseevich Manikhas12, V. McNally13, H. Forbes14, K. Shah15, Y. Yan15, G. McArthur16

Author affiliations

  • 1 Melanoma, Cancer Immunotherapy & Developmental Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", 80131 - Napoli/IT
  • 2 Dermatology, Gustave Roussy and Université Paris-Saclay, 94805 - Villejuif-Paris/FR
  • 3 Medical Oncology, University of Colorado Comprehensive Cancer Center, 80045 - Aurora/US
  • 4 Dermatology, Skin Cancer Center, Hannover Medical ScHaut-Tumour-Zentrum Hannover (HTZH), Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover (MHH)hool, Klinik für Dermatologie, Allergologie und Venerologie, 30625 - Hannover/DE
  • 5 Chemotherapy, Moscow City Oncology Hospital #62 of Moscow Healthcare Department, 143423 - Moscow/RU
  • 6 First Department Of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 - Athens/GR
  • 7 Department Of Chemotherapy And Innovative Technologies, N. N. Petrov National Medical Research Center of Oncology, 197758 - Saint-Petersburg/RU
  • 8 Medical Oncology, Hospital de Clínicas de Porto Alegre, 90035-007 - Porto Alegre/BR
  • 9 Dermatology, University Hospital Tübingen, 72074 - Tübingen/DE
  • 10 Department Of Soft Tissue/bone Sarcoma And Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 - Warsaw/PL
  • 11 Medical Oncology, N. N. Blokhin Russian Cancer Research Center, Ministry of Health, 115478 - Moscow/RU
  • 12 Medical Oncology, St. Petersburg Oncology Hospital, 190000 - St. Petersburg/RU
  • 13 Medical Oncology, Roche Products Ltd., AL7 1TW - Welwyn Garden City/GB
  • 14 Medical Oncology, Hoffmann-La Roche Limited, L5N 5M8 - Mississauga/CA
  • 15 Medical Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 16 Medical Oncology, Melanoma and Skin Service and Cancer Therapeutics Program, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU

Resources

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Abstract 1102P

Background

The phase III IMspire150 study (NCT02908672) demonstrated that combination therapy with inhibitors of PD-L1 (atezolizumab [A]), BRAF (vemurafenib [V]), and MEK (cobimetinib [C]) improved investigator-assessed PFS vs placebo (P)+V+C (hazard ratio [HR] 0.78; 95% CI 0.63-0.97; log-rank P=0.025). An exploratory analysis was conducted to define efficacy outcomes in key prognostic subgroups defined by baseline PD-L1 and LDH status.

Methods

Treatment-naive patients (pts) with unresectable stage IIIc/IV melanoma (AJCC 7th ed), measurable disease by RECIST 1.1, and BRAF V600 mutation–positive tumors were randomized 1:1 to receive A+V+C or P+V+C. PD-L1 expression was assessed using the anti–PD-L1 antibody SP142 (Ventana Medical Systems). PD-L1 status was defined based on the proportion of PD-L1–expressing tumor-infiltrating cells as PD-L1+ (≥1%) or PD-L1– (<1%). LDH levels were defined as high (>ULN ) or normal/low (≤ULN).

Results

Treatment benefit, as assessed by PFS and duration of response (DOR), favored the A+V+C arm over the P+V+C arm in all subgroups. Median PFS for A+V+C in the PD-L1– and PD-L1+ subgroups was 15.2 mo and 14.8 mo, respectively, at 18 mo follow-up (Table). In pts with LDH ≤ULN at baseline, PFS and DOR benefit with A+V+C were greater for the PD-L1+ subgroup. Conversely, in pts with LDH >ULN, benefit with A+V+C was greater in the PD-L1– subgroup.

Conclusions

Pts with PD-L1– tumors, which generally benefit less from immunotherapy alone, appear to derive similar clinical benefit from A+V+C as pts with PD-L1+ tumors. This effect was more evident among pts with high LDH levels, which is a known poor prognostic factor in pts with melanoma. Analyses are ongoing to identify other subgroups that may benefit from A+C+V. Table: 1102P

Subgroup Median PFS, months, n Median PFS, months, n HR (95%CI) Median DOR, months, n Median DOR, months, n HR (95%CI)
P+V+C A+V+C P+V+C A+V+C
All 10.6, 258 15.1, 256 0.77 (0.62-0.96) 12.6, 160 21.0, 169 0.68 (0.50-0.91)
PD-L1– 9.2, 86 15.2, 85 0.76 (0.53-1.10) 11.1, 51 19.1, 56 0.78 (0.47-1.30)
PD-L1+ 11.4, 158 14.8, 160 0.80 (0.60-1.06) 13.1, 102 22.4, 105 0.59 (0.41-0.87)
PD-L1–, LDH >ULN 5.6, 31 9.8, 27 0.53 (0.29-0.95) 5.2, 15 13.4, 18 0.40 (0.17-0.95)
PD-L1+, LDH >ULN 9.3, 49 6.3, 53 1.16 (0.75-1.80) 12.9, 31 12.9, 27 0.94 (0.49-1.81)
PD-L1–, LDH ≤ULN 11.9, 55 17.8, 58 0.93 (0.58-1.5) 19.5, 36 21.2, 38 0.94 (0.49-1.79)
PD-L1+, LDH ≤ULN 12.9, 109 22.7, 107 0.67 (0.46-0.96) 13.1, 71 N/A, 78 0.53 (0.34-0.85)

Clinical trial identification

NCT02908672.

Editorial acknowledgement

Medical editorial assistance was provided by Apothecom and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

P.A. Ascierto: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche-Genentech; Advisory/Consultancy: MSD; Advisory/Consultancy: Array; Advisory/Consultancy: Novartis; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Incyte; Advisory/Consultancy: Genmab; Advisory/Consultancy: NewLink Genetics; Advisory/Consultancy: MedImmune; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Syndax; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Idera; Advisory/Consultancy: Ultimovacs; Advisory/Consultancy: Sandoz; Advisory/Consultancy: Immunocore; Advisory/Consultancy: 4SC; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Italfarmaco. C. Robert: Advisory/Consultancy: BMS, Pierre Fabre, Novartis, Amgen, Merck, Roche, MSD, Sanofi, Biothera, Ultimovacs. K. Lewis: Advisory/Consultancy: Roche/Genentech. R. Gutzmer: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Non-remunerated activity/ies: BMS, Roche, Merck Serono, Amgen, Pierre Fabre, Sanofi Regeneron, MSD, Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Almirall Hermal, Pfizer, Sun Pharma, 4SC. H.J. Gogas: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS, MSD; Travel/Accommodation/Expenses: Roche; Honoraria (self): Novartis; Advisory/Consultancy: Amgen; Honoraria (self), Travel/Accommodation/Expenses: Pierre Fabre. R.P. Pereira: Honoraria (self), Advisory/Consultancy: Roche. T. Eigentler: Honoraria (self), Advisory/Consultancy: Roche, MSD, BMS, Novartis, Leo Pharma, Sanofi. P. Rutkowski: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis, BMS, Pierre Fabre; Honoraria (self), Speaker Bureau/Expert testimony: Roche, MSD; Honoraria (self), Advisory/Consultancy: Blueprint Medicines. V. McNally: Full/Part-time employment: Roche Ltd. H. Forbes: Full/Part-time employment: Hoffmann-La Roche Limited. K. Shah, Y. Yan: Full/Part-time employment: Genentech. G. McArthur: Research grant/Funding (institution): Array Biopharma, Roche/Genentech. All other authors have declared no conflicts of interest.

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