Central Nervous System

PV QA 2 - Poster Viewing Q&A 2

MO_14_2807 - Stereotactic Radiosurgery (SRS) with Immune Checkpoint Inhibitor Therapy (ICI) for Patients with Brain Metastasis (BM): The Impact of Timing and Sequencing

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Stereotactic Radiosurgery (SRS) with Immune Checkpoint Inhibitor Therapy (ICI) for Patients with Brain Metastasis (BM): The Impact of Timing and Sequencing
R. Kotecha1, J. M. Kim2, J. A. Miller3, S. T. Chao4, A. M. Mohammadi5, D. Peereboom6, E. S. Murphy4, J. H. Suh4, G. H. Barnett5, M. A. Vogelbaum5, L. Angelov5, and M. Ahluwalia6; 1Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, Miami, FL, 2Case Western Reserve University School of Medicine, Cleveland Clinic, Cleveland, OH, 3Department of Internal Medicine, Kaiser Permanente, San Francisco, CA, 4Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 5Department of Neurological Surgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, 6Department of Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

Purpose/Objective(s): The optimal timing and sequencing of ICI in patients with BM undergoing SRS is not adequately defined. We analyzed objective response rates in patients receiving ICI and SRS in order to determine sequencing and timing predictors for maximal intracranial control.

Materials/Methods: BM patients who underwent SRS and received ICI (PD1 or PDL1 inhibitor) were divided into three cohorts based on the timing of receipt of therapy: any therapy, “concurrent” (+/- ≤5 half-lives), or “immediate” (+/- one half-life) ICI. The primary outcome was magnitude of best objective lesion-specific response (BOR) (unidimensional RECIST). Secondary outcomes included the proportion of lesions achieving RECIST-defined complete (CR) or partial responses (PR), or stable (SD) or progressive disease (PD); response durability; rate of adverse radiation effects; and overall survival. Multivariable linear regression analysis for BOR was conducted on a per-lesion basis.

Results: 150 patients underwent SRS to 1003 brain metastases and received ICI during the course of their disease: 564 of the lesions (56%) were treated with SRS and "concurrent" ICI. 1,073 brain MRIs were reviewed, resulting in 5,508 measurements (average of 5.5 measurements per lesion, Range: 2-26). Lesions treated with SRS and “concurrent” ICI demonstrated superior BOR, overall objective response, and durable response. These findings were most pronounced among lesions treated with "immediate" ICI (BOR: -100 vs. -57%, p<0.001; CR: 50 vs. 32%; 6-month durable response: 89 vs. 74%, p<0.001; 12-month durable response: 94 vs. 71%, p<0.001). Among lesions with 12 months of follow-up (293, 29%), those treated with "immediate" ICI had a markedly improved CR rate (85 vs. 43%, p<0.001) and significantly reduced PD rate (4 vs. 19%, p<0.001). After adjusting for confounding covariates, “concurrent” ICI was associated with a 6 % improvement in BOR (p=0.040) and “immediate” ICI with a 11% improvement in BOR (p<0.001). Pre-exposed ICI lesions treated with SRS had poorer BOR (-45%) compared to ICI naive lesions (-63%, p<0.001), with the best response rates observed in ICI naive lesions receiving SRS and "immediate" ICI (-100%, p<0.001) with no added benefit to "immediate" neoadjuvant ICI (-100%, p=0.52). Significant differences in response rates were observed across primary tumor histologies and different ICI agents. The 24-month cumulative incidence of adverse radiation effects with death as a competing risk was low among patients receiving "concurrent" (3.3%) or "immediate" ICI (3.6%).

Conclusion: This study demonstrates that the timing of ICI and SRS in patients with brain metastasis is associated with overall response, best response, and durability of response with the most substantial effect in ICI naive patients undergoing "immediate" combined modality therapy, which is also tolerated well. Further analysis will help to individualize strategies for the optimal sequencing of systemic therapy based on tumor histology and the selected agent.

Author Disclosure: R. Kotecha: Honoraria; Elsevier Practice Update. J.M. Kim: None. J.A. Miller: None. S.T. Chao: Honoraria; Varian Medical Systems, Zeiss, Abbvie. Consultant; Abbvie. A.M. Mohammadi: None. D. Peereboom: Research Grant; Bristol Myers-Squibb, Genentech, Neonc Technologies, Novartis, Orbus Therapeutics, Pfizer, Stemline Therapeutics. Consultant; Abbvie. J.H. Suh: Consultant; ACMUI. Board member; Korean American Society for Therapeutic Radiation. G.H. Barnett: Consultant; Monteris Medical, Inc. Royalty; Mako Surgical Corp, Roche. M.A. Vogelbaum: Equity and royalty interests, company founder and officer ; Infuseon Therapeutics, Inc. Royalty; Infuseon Therapeutics, Inc. Royalty, equity, fiduciary role; Vivere Pharma, Inc. Chair; Neurosurgery Committee for NRG Oncology. L. Angelov: None. M. Ahluwalia: Research Grant; Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Spectrum Pharmaceuticals, Tracon Pharmaceuticals, Novocure. Consultant; Merck, Genentech, Roche, Incyte, Caris Lifesciences, Monteris Medical, MRI interventions Inc. Consult and research grant; Elekta. Chair of the Education Committe; American Society of Clinical Oncology. Chair of the Education Day, Annual Meeting; Society of NeuroOncology.

Send Email for Rupesh Kotecha


Assets

MO_14_2807 - Stereotactic Radiosurgery (SRS) with Immune Checkpoint Inhibitor Therapy (ICI) for Patients with Brain Metastasis (BM): The Impact of Timing and Sequencing



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for Stereotactic Radiosurgery (SRS) with Immune Checkpoint Inhibitor Therapy (ICI) for Patients with Brain Metastasis (BM): The Impact of Timing and Sequencing