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Poster display

1436 - Prognostic subgroups and impact of treatment for post-progression overall survival (ppOS) in patients (pts) with BRAFV600-mutated metastatic melanoma treated with dacarbazine (DTIC) or vemurafenib (VEM) ± cobimetinib (COBI): A pooled analysis


09 Oct 2016


Poster display


Paolo Ascierto


Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379


P.A. Ascierto1, A. Ribas2, J. Larkin3, G.A. McArthur4, K.D. Lewis5, A. Hauschild6, K.T. Flaherty7, E. McKenna8, Q. Zhu8, Y. Mun8, B. Dréno9

Author affiliations

  • 1 Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 2 Medicine, Hematology & Oncology, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles/US
  • 3 Medicine, Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 4 Oncology, Peter McCallum Cancer Centre, East Melbourne/AU
  • 5 Oncology, University of Colorado Comprehensive Cancer Center, Aurora/US
  • 6 Department Of Dermatology, University Hospital Schleswig-Holstein, 24105 - Kiel/DE
  • 7 Medicine, Massachusetts General Hospital, Boston/US
  • 8 Medical Affairs, Genentech, Inc., South San Francisco/US
  • 9 Dermato Cancerology, Nantes University, Nantes/FR


Abstract 1436


A pooled analysis of pts treated with DTIC, VEM, or COBI + VEM in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies was performed to identify pt subgroups prognostic for ppOS, defined as time from progression (PD) to death from any cause. The impact of post-progression treatment (ppRx) on ppOS was also assessed.


All eligible pts with PD were included. Recursive partitioning for censored response variable in a conditional inference framework was performed to model relationships between prespecified covariates (at baseline or PD, initial treatment, and ppRx) and ppOS. Identified subgroups were applied to pooled treatment cohorts (DTIC, VEM, or COBI + VEM). ppRx was defined as ≥1 dose of immunotherapy (IT), targeted therapy (TT), or other (including IT + TT or no treatment) within 90 days after PD.


In a pooled analysis of all pts (N = 809), baseline lactate dehydrogenase (LDH) level (normal, elevated ≤2× upper limit of normal [ULN], or >2× ULN), Eastern Cooperative Oncology Group performance status (ECOG PS) at PD (0 vs >0), baseline disease stage (IIIC/M1a/M1b vs M1c), and ppRx (IT/TT vs other) were significant prognostic factors for ppOS, producing 7 pt subgroups. Among all pts, 169 received IT (ipilimumab in 96%), 32 received TT, and 608 received other ppRx. After adjusting for other covariates (including initial treatment), ppRx with IT/TT was associated with longer ppOS. Pooled data for all pts, VEM and DTIC cohorts are in the Table. ppOS data for the COBI + VEM cohort were immature, but followed a similar pattern.

ppOS: Pooled Analysis of All pts and VEM and DTIC Cohorts

Prognostic Subgroup All pts VEM Cohort DTIC Cohort
N (events) ppOS, median, mo (95% CI) 3-year ppOS, % (95% CI) N (events) ppOS, median, mo (95% CI) 3-year ppOS, % (95% CI) N (events) ppOS, median, mo (95% CI) 3-year ppOS, % (95% CI)
Normal LDH + stage IIIC/M1a/M1b 196 (127) 11.8 (9.7-15.1) 22.2 (16.0-30.8) 108 (66) 11.2 (9.4-15.6) 22.3 (13.9-36.0) 58 (45) 13.0 (9.1-21.5) 24.6 (15.6-38.8)
Normal LDH + stage M1c + ppRx IT/TT 64 (46) 11.8 (9.9-16.1) 22.4 (13.4-37.7) 35 (25) 12.5 (10.4-19.9) 21.3 (10.3-44.1) 18 (18) 12.3 (9.7-NE) 25.9 (11.5-58.3)
Normal LDH + stage M1c + ppRx other + ECOG PS at PD 0 84 (67) 7.5 (5.8-12.2) 4.9 (1.4-17.4) 50 (42) 7.5 (5.2-13.2) 3.9 (0.6-24.0) 14 (13) 7.2 (5.8-17.7) 7.1 (1.1-47.2)
Normal LDH + stage M1c + ppRx other + ECOG PS at PD >0 71 (66) 3.6 (3.0-5.5) 1.8 (0.3-12.4) 41 (37) 4.6 (3.2-7.0) 3.9 (0.6-24.3) 19 (19) 3.4 (2.2-15.7) NE (NE-NE)
Elevated LDH (≤2× ULN) + ppRx IT/TT 64 (50) 7.9 (6.7-12.5) 7.8 (2.4-24.9) 37 (29) 8.9 (6.7-16.0) NE (NE-NE) 14 (12) 6.6 (4.9-NE) 14.3 (4.0-51.5)
Elevated LDH (≤2× ULN) + ppRx other 188 (161) 4.5 (3.7-5.2) NE (NE-NE) 99 (82) 3.7 (2.9-5.0) NE (NE-NE) 47 (46) 4.7 (3.8-6.6) NE (NE-NE)
Elevated LDH (>2× ULN) 142 (131) 2.3 (1.9-2.9) 4.5 (2.0-10.1) 89 (84) 2.4 (1.9-3.3) 3.9 (1.3-11.4) 25 (23) 2.4 (1.3-7.5) NE (NE-NE)

Abbreviations: CI, confidence interval; NE, not estimable.


A combination of LDH, disease stage at baseline, ppRx, and ECOG PS at PD identified 7 pt subgroups prognostic for ppOS. After adjusting for other covariates, ppRx was associated with ppOS, with similar results in DTIC and VEM cohorts.

Clinical trial identification

Legal entity responsible for the study

F. Hoffman-La Roche, Ltd.


F. Hoffman-La Roche, Ltd.


P.A. Ascierto: Consultant Or Advisory Role: BMS, Roche/Genentech, MSD, Ventana, Novartis, Amgen, and Array); Research funding (institution): BMS, Roche/Genentech, and Ventana. A. Ribas: Stock or Other Ownership: Compugen, CytomX, Five Prime, and Kite Pharma; Consulting or Advisory Role: Pfizer, Merck, Amgen, and Roche. J. Larkin: Institutional research support from MSD, BMS, Pfizer, and Novartis and nonremunerated consultancy for GSK, Novartis, MSD, BMS, Pfizer, and Roche/Genentech. G.A. McArthur: Consulting or Advisory Role: Provectus; Research Funding: Pfizer, Celgene, and Ventana; Travel, Accommodations, Expenses: Roche and Novartis. K.D. Lewis: Honoraria and Advisory Board: Roche/Genentech. A. Hauschild: Consulting or Advisory Role, Honoraria, and Travel Grants: Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, and Roche Pharma. K.T. Flaherty: Consultant, honoraria: Roche/Genentech. E. McKenna, Y. Mun: Employment and stock or other ownership: Genentech/Roche. Q. Zhu: Employment: Genentech/Roche. B. Dréno: Consulting or advisory role: BMS, GSK, Roche, Novartis; speakers' bureau: BMS, GSK, Roche; research funding: BMS, GSK; travel, accommodations, expenses: BMS, Roche.

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