TY - JOUR
T1 - Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma brain metastases
AU - Hilbers, Marie Luise
AU - Dimitriou, Florentia
AU - Lau, Peter
AU - Bhave, Prachi
AU - McArthur, Grant A.
AU - Zimmer, Lisa
AU - Kudura, Ken
AU - Gérard, Camille L.
AU - Levesque, Mitchell P.
AU - Michielin, Olivier
AU - Dummer, Reinhard
AU - Cheng, Phil F.
AU - Mangana, Joanna
N1 - Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The melanoma registry database of the Department of Dermatology Zurich has been partially supported by an unrestricted grant to the University of Zurich from Amgen , Novartis , BMS , MSD and Pierre Fabre .
Funding Information:
The authors thank Mrs. Isabell Pieper Scholz for her contribution to the melanoma registry database. FD is supported by the Swiss Academy of Medical Sciences (SAMS) and G. and J. Bangerter-Rhyner Foundation ( YTCR 22/19 ).
Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The melanoma registry database of the Department of Dermatology Zurich has been partially supported by an unrestricted grant to the University of Zurich from Amgen, Novartis, BMS, MSD and Pierre Fabre.GAM has been a consultant or advisor for Provectus; received research funding from Pfizer, Celgene, and Ventana; and has had travel accommodation and expenses paid for by Roche and Novartis.OM reports grants and personal fees from Bristol Myers Squibb (BMS), grants and personal fees from MSD, personal fees from Roche, outside the submitted work.The authors thank Mrs. Isabell Pieper Scholz for her contribution to the melanoma registry database. FD is supported by the Swiss Academy of Medical Sciences (SAMS) and G. and J. Bangerter-Rhyner Foundation (YTCR 22/19).
Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - Background: Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune checkpoint inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM. Methods: MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: 53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6- (46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of patients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2–7.6) and mOS 14.2 months (95% CI 8.99–26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI. Conclusion: Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice.
AB - Background: Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune checkpoint inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM. Methods: MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: 53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6- (46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of patients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2–7.6) and mOS 14.2 months (95% CI 8.99–26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI. Conclusion: Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice.
KW - Immunotherapy
KW - Melanoma brain metastasis
KW - Stereotactic radiosurgery
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85113374213&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2021.07.028
DO - 10.1016/j.ejca.2021.07.028
M3 - Article
C2 - 34454317
SN - 0959-8049
VL - 156
SP - 149
EP - 163
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -