Abstract 3560
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 BEAT-MBM 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 + 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 + Nivo. The remaining 23 pts received either targeted therapy (6), radiation alone (2), other immunotherapy +/- 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 + 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 on-protocol therapy in this vulnerable population.
Clinical trial identification
CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058).
Editorial acknowledgement
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.
Resources from the same session
2673 - Clinical activity of vofatamab (V), an FGFR3 selective antibody in combination with pembrolizumab (P) in metastatic urothelial carcinoma (mUC), updated interim analysis of FIERCE-22
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract