The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study

Martins, Filipe; Schiappacasse, Luis; Levivier, Marc; Tuleasca, Constantin; Cuendet, Michel A.; Aedo-Lopez, Veronica; Moura, Bianca Gautron; Homicsko, Krisztian; Bettini, Adrienne; Berthod, Grégoire; Gérard, Camille L.; Wicky, Alexandre; Bourhis, Jean; Michielin, Olivier

doi:10.1007/s11060-019-03363-0

Cited by 21 publications

(8 citation statements)

References 32 publications

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“…For MAPKi vs. no MAPKi, meta-analysis showed meta-HR of 0.45 (95% CI, 0.28-0.73; n=2) ( 43 , 50 ). However, no significant improvement OS from date of diagnosis was observed for SRS vs. WBRT or for SRS+MAPKi vs. SRS alone ( 39 – 42 , 50 ).…”

Section: Resultsmentioning

confidence: 89%

“…Meta-analysis results by treatment for OS from date of diagnosis showed similar results. For the OS from date of diagnosis, treatment with SRS+IO vs. SRS alone had meta-HR of 0.34 (95% CI, 0.15-0.81; n=3) ( Table 2 , Figure S2 ), and IO alone vs. no IO had a meta-HR of 0.62 (95% CI, 0.45-0.86; n=4) ( Table 2 , Figure S6 ) ( 39 , 41 , 42 ). For MAPKi vs. no MAPKi, meta-analysis showed meta-HR of 0.45 (95% CI, 0.28-0.73; n=2) ( 43 , 50 ).…”

Section: Resultsmentioning

confidence: 99%

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Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases

Tan

Scherrer

et al. 2022

Front. Oncol.

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BackgroundMore than 60% of all stage IV melanoma patients develop brain metastases, while melanoma brain metastases (MBM) is historically difficult to treat with poor prognosis.ObjectivesTo summarize clinical outcomes and prognostic factors in MBM patients.MethodsA systematic review with meta-analysis was conducted, and a literature search for relevant studies was performed on November 1, 2020. Weighted average of median overall survival (OS) was calculated by treatments. The random-effects model in conducting meta-analyses was applied.ResultsA total of 41 observational studies and 12 clinical trials with our clinical outcomes of interest, and 31 observational studies addressing prognostic factors were selected. The most common treatments for MBM were immunotherapy (IO), MAP kinase inhibitor (MAPKi), stereotactic radiosurgery (SRS), SRS+MAPKi, and SRS+IO, with median OS from treatment start of 7.2, 8.6, 7.3, 7.3, and 14.1 months, respectively. Improved OS was observed for IO and SRS with the addition of IO and/or MAPKi, compared to no IO and SRS alone, respectively. Several prognostic factors were found to be significantly associated with OS in MBM.ConclusionThis study summarizes pertinent information regarding clinical outcomes and the association between patient characteristics and MBM prognosis.

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases

Tan

Scherrer

et al. 2022

Front. Oncol.

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“…In prior studies of the safety of combinations of checkpoint inhibitors and radiosurgery the interval studied between therapies has varied from 2 weeks to 5.5 months or even any interval. [10][11][12][13] In this study, we selected an interval of 4 months to capture the full acute toxicity window and allow for a long half-life with the potential that residual changes to the immune system may affect toxicity later than other therapies. Patient characteristics collected included driver mutation status (BRAF, ALK, EGFR); PD-L1 expression percentage (for NSCLC); absolute lymphocyte count; and Karnofsky performance status.…”

Section: Methods and Materials Patientsmentioning

confidence: 99%

Control and Toxicity in Melanoma Versus Other Brain Metastases in Response to Combined Radiosurgery and PD-(L)1 Immune Checkpoint Inhibition

Travis

Marcrom

Brown

et al. 2021

Advances in Radiation Oncology

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Purpose Prior studies have mixed conclusions about the efficacy and central nervous system (CNS) toxicity profile of combining radiosurgery with anti-programed cell death 1 (PD-1) immune checkpoint inhibition (ICI) for brain metastases. This study evaluates the safety and efficacy of combined radiosurgery and anti-PD-1 ICI for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) brain metastases (BM). Methods and Materials Forty-one patients with 153 radiation naïve melanoma BM and 33 patients with 118 BM of NSCLC and RCC origin from 2014 through 2019 received radiosurgery and either anti PD-1 receptor inhibition or anti PD-L1 inhibition targeting the PD-1 ligand with less than 4 months separating either therapy. Similar to Radiation Therapy Oncology Group 9005, high-grade CNS toxicity was defined as irreversible grade 3 or any grade 4/5 neurologic event. Salvage resection revealing necrosis and viable tumor was considered grade 4 toxicity and local failure. An increase in greatest cross-sectional diameter of 25% on contrasted magnetic resonance imaging was designated as a local failure. Results Median follow-up was 10 months (range, 1-41 months). Local control was estimated to be 90.3% at 1 year. Distant control was 38.8% at 1 year, and neither local nor distant control were significantly influenced by limiting steroids to the day of treatment ( P = .55, .52 respectively). One-year freedom from high-grade toxicity was 90.4% for patients and 94.6% for tumors. Though melanoma accounted for 41 (55%) patients and 153 (56%) tumors, it accounted for all high-grade toxicities ( P = .03). These patients had some combination of high tumor burden, aggressive steroid taper, and treatment with ipilimumab. Conclusions Stereotactic radiosurgery combined with anti-PD-1 ICI appears to result in a high rate of local tumor control and a low rate of high-grade CNS toxicity, comparable to historical series with radiosurgery alone. High-grade toxicity is more likely in melanoma than RCC and NSCLC. Coming prospective studies will shed light on further questions about treatment timing, steroids, and response.

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“…In addition, the sequence of radiotherapy and administration of ICIs is deficient. Especially, several studies have reported significant impacts on survival outcomes of different sequences of ICIs and radiotherapy (25,26). Fourth, several newer PD-1/PD-L1 inhibitors were not included in this study, including cemiplimab, due to their relatively late approval.…”

Section: Limitations Of the Studymentioning

confidence: 99%

A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors

Sirbu

Lucas

et al. 2021

Front. Oncol.

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IntroductionBrain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed.MethodsVariables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified.ResultsA total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85–0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82–0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82–0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73–0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86–1.10).ConclusionsOverall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.

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The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study

Cited by 21 publications

References 32 publications

Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases

Systematic literature review and meta-analysis of clinical outcomes and prognostic factors for melanoma brain metastases

Control and Toxicity in Melanoma Versus Other Brain Metastases in Response to Combined Radiosurgery and PD-(L)1 Immune Checkpoint Inhibition

A Retrospective Study of Brain Metastases From Solid Malignancies: The Effect of Immune Checkpoint Inhibitors

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