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Outcomes of patients with melanoma brain metastases (MBM) treated with standard of care therapy after being excluded from MBM-specific clinical trials
abstracts
Annals of Oncology Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Intracranial anti-tumour activity in melanoma brain metastases with encorafenib plus binimetinib: A multicenter, retrospective analysis
Background: Over 60% of patients (pts) with stage IV melanoma may develop brain metastases, resulting in a significantly increased morbidity and poor overall prognosis. Clinical data for melanoma brain metastases (MBM) treatments are limited, as controlled studies often exclude pts with untreated brain metastases. Methods: We conducted a multicenter, retrospective case series investigation with consecutive pts with BRAF-mutant MBM who were treated with BRAF inhibitor encorafenib plus MEK inhibitor binimetinib to evaluate the antitumor response with this combination. Assessments included intracranial, extracranial & global objective response rates (ORRs; percentage of complete [CR] þ partial [PR] responses) evaluated by modified RECIST version 1.1; clinical benefit rate (CBR; percentage of CR þ PR þ stable disease [SD] as best response); time to response, duration of response, and safety. Results: A total of 17 pts with stage IV BRAF-mutant MBM who received encorafenib plus binimetinib in centers in the United States were included. Pts had received a median of 2 prior lines of treatment over a median of 520 days since their melanoma diagnosis (median of 55 days since diagnosis of MBM). Of the patients included, 82% had prior treatment with BRAF/MEK inhibitors. The intracranial ORR was 35% (with 3 CRs and 3 PRs) and CBR was 76%, with a median duration of response of 17 weeks. Eight pts with either stable disease or a response were still ongoing treatment at the time of this analysis. Among the 14 MBM pts with prior BRAF/MEK inhibitor treatment, the intracranial ORR was 21% and CBR was 71%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in pts with melanoma without brain metastases. Conclusions: Combination therapy with encorafenib plus binimetinib elicited intracranial activity in pts with BRAF-mutant MBM, including in pts previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted. *K. Holbrook and J. Lutzky are co-first authors. Editorial acknowledgement: Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma. Legal entity responsible for the study: Array BioPharma Inc. Funding: Array BioPharma. Disclosure: J. Lutzky: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma; Advisory / Consultancy, Speaker Bureau / Expert testimony: Regeneron; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Bristol-Myers Squibb. A. Amin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Regeneron. J.M. Davis: Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy: Array BioPharma. M.A. Davies: Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Syndax; Non-remunerated activity/ies: Nanostring. A. Diab: Advisory / Consultancy: Array BioPharma. I.C. Glitza: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma. R.N. Amaria: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Iovance. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy, DSMB: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution), DSMB: Reata. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GSK. All other authors have declared no conflicts of interest.
Outcomes of patients with melanoma brain metastases (MBM) treated with standard of care therapy after being excluded from MBM-specific clinical trials
K. Holbrook, M.P. Shephard, L. Haydu, I. Glitza Oliva, R.N. Amaria, S. Patel, A. Diab, P. Hwu, C. Brown, I. Boesch Arnold, E. Burton, M.A. Davies, H.A. Tawbi Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, TX, USA Background: Brain metastases are a known complication of metastatic melanoma and often result in debilitating neurological conditions or death. Pts with MBM are typically excluded from trials, however, MBM-specific trials have been designed to assess the impact of systemic therapy in this challenging population. Combination immunotherapy has demonstrated a high rate of intracranial activity in pts with asymptomatic MBMs. However, many do not quallify during the screening period and never initiate protocol. We sought to determine the treatment patterns and therapeutic outcomes in pts considered for MBM-specific trials but screen failed before initiating treatment. Methods: We reviewed the outcomes of pts considered for 2 MBM-specific trials that enrolled pts with untreated MBM at MD Anderson Cancer Center, CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Both studies had cohorts that allowed symptomatic pts or pts requiring steroids. We performed a retrospective medical record review of pts who failed screening to CM204 and BEAT-MBM. Results: We initially screened 65 pts and 38 screen-failed: 17 pts (50%) for BEATMBM and 21 pts (68%) for CM204. Of these, 15 received Ipi, Nivo, or combination off study. 5 (33%) responded to treatment and have maintained response. 10 pts received Ipi þ Nivo and 3 (30%) of these maintained durable responses. 2 received Ipi alone (13%) and 3 received Nivo alone (20%). All pts received systemic therapy before radiation. Of the 5 responders, 2 received WBXRT after Ipi þ Nivo. The remaining 23 pts received either targeted therapy (6), radiation alone (2), other immunotherapy þ/radiation (3), or no treatment (12). Conclusions: Given the limited number of trials available to pts with MBM and high rate of screen failure (over 50% in our population), there is an unmet need that needs to be addressed. Of those patients that fail screening, many are eligible for systemic therapy off protocol. Pts with MBM treated with Ipi þ Nivo off study still experienced therapeutic benefit. Given the high rate of screen failure in pts with MBM, there is a need for modification for eligibility criteria and the screening process to expedite onprotocol therapy in this vulnerable population. Clinical trial identification: CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Legal entity responsible for the study: The University of Texas M.D. Anderson Cancer Center. Funding: The University of Texas MD Anderson Cancer Center, Bristol-Myers Squibb, Genentech. Disclosure: I. Glitza Oliva: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array; Advisory / Consultancy, Research grant / Funding (self): BMS; Research grant / Funding (self): Merck. R.N. Amaria: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Array. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution): Reata; Research grant / Funding (institution): Novartis. P. Hwu: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Iovance Biotherapeutics; Shareholder / Stockholder / Stock options: Immatics; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Sanofi. M.A. Davies: Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy: Array Biopharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Oncothyreon; Research grant / Funding (self): Myriad Genetics; Research grant / Funding (self): Sanofi. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glaxosmithkline. All other authors have declared no conflicts of interest.
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The analysis of current treatment outcomes in melanoma patients with brain metastases
J. Placzke, P. Teterycz, I. Lugowska, T. Morysinski, A. Borkowska, T. Switaj, A. Klimczak, K. Kozak, P. Rogala, H. Kosela-Paterczyk, M.E. Dudzisz-Sledz, M. Spalek, A.M. Czarnecka, P. Rutkowski Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie Institute - Oncology Centre (MSCI), Warsaw, Poland Background: The risk of brain metastases (BM) in advanced melanoma (MM) is 4050%. Historical median survival of MM patients (pts) with BMs was 4-5 months. Current systemic treatments with targeted therapy and immunotherapy prolong survival up to > 2 years, while prognosis of BMs carrying pts is not fully defined and optimal treatment sequencing remain unknown. We aimed to analyze the contemporary treatment outcomes in this specific group of pts.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz255 | v555
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz255.049/5576290 by guest on 24 October 2019
J. Lutzky1, K. Holbrook2, A. Amin3, J.M. Davis3, M.A. Davies2, A. Diab2, I.C. Glitza2, R.N. Amaria2, S. Patel2, H.A. Tawbi2 1 Medical Oncology, Mount Sinai Comprehensive Cancer Center, Miami Beach, FL, USA, 2 Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3Atrium Health, Levine Cancer Institute, Charlotte, NC, USA
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Annals of Oncology Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1360P
Intracranial anti-tumour activity in melanoma brain metastases with encorafenib plus binimetinib: A multicenter, retrospective analysis
Background: Over 60% of patients (pts) with stage IV melanoma may develop brain metastases, resulting in a significantly increased morbidity and poor overall prognosis. Clinical data for melanoma brain metastases (MBM) treatments are limited, as controlled studies often exclude pts with untreated brain metastases. Methods: We conducted a multicenter, retrospective case series investigation with consecutive pts with BRAF-mutant MBM who were treated with BRAF inhibitor encorafenib plus MEK inhibitor binimetinib to evaluate the antitumor response with this combination. Assessments included intracranial, extracranial & global objective response rates (ORRs; percentage of complete [CR] þ partial [PR] responses) evaluated by modified RECIST version 1.1; clinical benefit rate (CBR; percentage of CR þ PR þ stable disease [SD] as best response); time to response, duration of response, and safety. Results: A total of 17 pts with stage IV BRAF-mutant MBM who received encorafenib plus binimetinib in centers in the United States were included. Pts had received a median of 2 prior lines of treatment over a median of 520 days since their melanoma diagnosis (median of 55 days since diagnosis of MBM). Of the patients included, 82% had prior treatment with BRAF/MEK inhibitors. The intracranial ORR was 35% (with 3 CRs and 3 PRs) and CBR was 76%, with a median duration of response of 17 weeks. Eight pts with either stable disease or a response were still ongoing treatment at the time of this analysis. Among the 14 MBM pts with prior BRAF/MEK inhibitor treatment, the intracranial ORR was 21% and CBR was 71%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in pts with melanoma without brain metastases. Conclusions: Combination therapy with encorafenib plus binimetinib elicited intracranial activity in pts with BRAF-mutant MBM, including in pts previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted. *K. Holbrook and J. Lutzky are co-first authors. Editorial acknowledgement: Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma. Legal entity responsible for the study: Array BioPharma Inc. Funding: Array BioPharma. Disclosure: J. Lutzky: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma; Advisory / Consultancy, Speaker Bureau / Expert testimony: Regeneron; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Bristol-Myers Squibb. A. Amin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Regeneron. J.M. Davis: Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy: Array BioPharma. M.A. Davies: Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Syndax; Non-remunerated activity/ies: Nanostring. A. Diab: Advisory / Consultancy: Array BioPharma. I.C. Glitza: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma. R.N. Amaria: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Iovance. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy, DSMB: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution), DSMB: Reata. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GSK. All other authors have declared no conflicts of interest.
Outcomes of patients with melanoma brain metastases (MBM) treated with standard of care therapy after being excluded from MBM-specific clinical trials
K. Holbrook, M.P. Shephard, L. Haydu, I. Glitza Oliva, R.N. Amaria, S. Patel, A. Diab, P. Hwu, C. Brown, I. Boesch Arnold, E. Burton, M.A. Davies, H.A. Tawbi Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, TX, USA Background: Brain metastases are a known complication of metastatic melanoma and often result in debilitating neurological conditions or death. Pts with MBM are typically excluded from trials, however, MBM-specific trials have been designed to assess the impact of systemic therapy in this challenging population. Combination immunotherapy has demonstrated a high rate of intracranial activity in pts with asymptomatic MBMs. However, many do not quallify during the screening period and never initiate protocol. We sought to determine the treatment patterns and therapeutic outcomes in pts considered for MBM-specific trials but screen failed before initiating treatment. Methods: We reviewed the outcomes of pts considered for 2 MBM-specific trials that enrolled pts with untreated MBM at MD Anderson Cancer Center, CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Both studies had cohorts that allowed symptomatic pts or pts requiring steroids. We performed a retrospective medical record review of pts who failed screening to CM204 and BEAT-MBM. Results: We initially screened 65 pts and 38 screen-failed: 17 pts (50%) for BEATMBM and 21 pts (68%) for CM204. Of these, 15 received Ipi, Nivo, or combination off study. 5 (33%) responded to treatment and have maintained response. 10 pts received Ipi þ Nivo and 3 (30%) of these maintained durable responses. 2 received Ipi alone (13%) and 3 received Nivo alone (20%). All pts received systemic therapy before radiation. Of the 5 responders, 2 received WBXRT after Ipi þ Nivo. The remaining 23 pts received either targeted therapy (6), radiation alone (2), other immunotherapy þ/radiation (3), or no treatment (12). Conclusions: Given the limited number of trials available to pts with MBM and high rate of screen failure (over 50% in our population), there is an unmet need that needs to be addressed. Of those patients that fail screening, many are eligible for systemic therapy off protocol. Pts with MBM treated with Ipi þ Nivo off study still experienced therapeutic benefit. Given the high rate of screen failure in pts with MBM, there is a need for modification for eligibility criteria and the screening process to expedite onprotocol therapy in this vulnerable population. Clinical trial identification: CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Legal entity responsible for the study: The University of Texas M.D. Anderson Cancer Center. Funding: The University of Texas MD Anderson Cancer Center, Bristol-Myers Squibb, Genentech. Disclosure: I. Glitza Oliva: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array; Advisory / Consultancy, Research grant / Funding (self): BMS; Research grant / Funding (self): Merck. R.N. Amaria: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Array. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution): Reata; Research grant / Funding (institution): Novartis. P. Hwu: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Iovance Biotherapeutics; Shareholder / Stockholder / Stock options: Immatics; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Sanofi. M.A. Davies: Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy: Array Biopharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Oncothyreon; Research grant / Funding (self): Myriad Genetics; Research grant / Funding (self): Sanofi. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glaxosmithkline. All other authors have declared no conflicts of interest.
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The analysis of current treatment outcomes in melanoma patients with brain metastases
J. Placzke, P. Teterycz, I. Lugowska, T. Morysinski, A. Borkowska, T. Switaj, A. Klimczak, K. Kozak, P. Rogala, H. Kosela-Paterczyk, M.E. Dudzisz-Sledz, M. Spalek, A.M. Czarnecka, P. Rutkowski Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie Institute - Oncology Centre (MSCI), Warsaw, Poland Background: The risk of brain metastases (BM) in advanced melanoma (MM) is 4050%. Historical median survival of MM patients (pts) with BMs was 4-5 months. Current systemic treatments with targeted therapy and immunotherapy prolong survival up to > 2 years, while prognosis of BMs carrying pts is not fully defined and optimal treatment sequencing remain unknown. We aimed to analyze the contemporary treatment outcomes in this specific group of pts.
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz255 | v555
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz255.049/5576290 by guest on 24 October 2019
J. Lutzky1, K. Holbrook2, A. Amin3, J.M. Davis3, M.A. Davies2, A. Diab2, I.C. Glitza2, R.N. Amaria2, S. Patel2, H.A. Tawbi2 1 Medical Oncology, Mount Sinai Comprehensive Cancer Center, Miami Beach, FL, USA, 2 Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, 3Atrium Health, Levine Cancer Institute, Charlotte, NC, USA
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