Management of Brain Metastases in the New Era of Checkpoint Inhibition

Lauko, Adam; Thapa, Bicky; Venur, Vyshak Alva; Ahluwalia, Manmeet

doi:10.1007/s11910-018-0877-8

Cited by 32 publications

(48 citation statements)

References 60 publications

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“…In the 14 patients with initial CNS involvement, median OS was significantly worse (3.7 months; range 1.5-7) compared to the whole cohort (8.7 months; range 7.7-9.9) [61]. At least 16 trials investigating ICB efficacy for brain metastases are ongoing; however, none address this question in patients with mUC [62]. Whether first-or second-line ICB treats or prevents intracranial failures in mUC is currently unknown.…”

Section: Systemic Therapymentioning

confidence: 99%

Review: Brain Metastases in Bladder Cancer

Brenneman

Christodouleas

Sargos

et al. 2020

BLC

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Nearly 50% of bladder cancer patients either present with metastatic disease or relapse distantly following initial local therapy. Prior to platinum-based chemotherapy, the incidence of bladder cancer central nervous system metastases was approximately 1%; however, their incidence has increased to 3–16% following definitive treatment as platinum-based regimens have changed the natural history of the disease. Bladder cancer brain metastases are generally managed similarly to those from more common malignancies such as non-small cell lung cancer, with surgery +/–adjuvant radiotherapy, or radiotherapy alone using stereotactic radiosurgery or whole brain radiotherapy. Limited data suggest that patients with inoperable urothelial carcinoma brain metastases who are not candidates for stereotactic radiosurgery may benefit from shorter whole brain radiation therapy courses compared to other histologies, but data is hypothesis-generating. Given improvements in the efficacy of systemic therapy and supportive care strategies for metastatic urothelial carcinoma translating in improved survival, the incidence of intracranial failures may increase. Immune checkpoint blockade therapy may benefit cisplatin-ineligible metastatic urothelial carcinoma patients as first-line therapy; however, the effectiveness of immune checkpoint blockade to treat central nervous system disease has not been established. In this review, we discuss the incidence and management of bladder cancer brain metastases and considerations regarding variations in management relative to more commonly encountered non-urothelial histologies.

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Section: Systemic Therapymentioning

confidence: 99%

Review: Brain Metastases in Bladder Cancer

Brenneman

Christodouleas

Sargos

et al. 2020

BLC

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“…Several trials are ongoing to investigate the efficacy, safety, proper timing of combination of radiotherapy, and immunotherapy [62]. The results of these studies will help evaluate the status of this therapy for brain metastases.…”

Section: Combined Immunotherapy and Radiotherapymentioning

confidence: 99%

Management of brain metastases: history and the present

2019

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Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer. With the application of novel systematic therapy and improvement of overall survival, the prevalence of brain metastases is increasing. The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy. Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month. The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4-6 months in the 1980s. Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance. With the development of stereotactic radiosurgery, stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival. In addition, stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection. With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis, novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases. Clinical trials had revealed the efficacy of targeted therapy. Furthermore, the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation. Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.

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“…The immune system has its inherent immunosuppressive mechanisms or uses checkpoints to limit prolonged immune activation and inflammation, which could be detrimental to the host. 10 Tumors have co-opted these endogenous mechanisms as a means to evade immune surveillance by the host immune system. During the past decade, novel drugs targeting checkpoint pathways leading to a reinvigorated antitumor immune response have shown promising efficacy in advanced NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…During the past decade, novel drugs targeting checkpoint pathways leading to a reinvigorated antitumor immune response have shown promising efficacy in advanced NSCLC. 10,11 Among immune therapies, the programmed cell death 1 (PD-1) and the programmed cell death receptor 1 (PD-L1) blockade therapies are the most investigated. Preclinical studies have demonstrated that PD-1 receptor has emerged as a dominant negative regulator of antitumor T-cell effector function when engaged by its ligand PD-L1.…”

Section: Introductionmentioning

confidence: 99%

<p>Complete response associated with immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis of nine randomized controlled trials</p>

Li¹,

He²,

Xiu³

et al. 2019

CMAR

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The purposes of this study were to investigate whether the use of immune checkpoint inhibitors (ICIs) in advanced non-small-cell lung cancer (NSCLC) would increase the possibility of archiving complete response (CR) and assess the surrogate end points for overall survival (OS). Methods: We calculated the incidence and relative risk (RR) of CR events in patients assigned to ICIs compared to that in controls. Simple linear regression models were fitted for median OS and each surrogate (median progression-free survival [PFS], CRs, and objective response rate [ORR]). Results: A total of 4,803 NSCLC patients from nine randomized controlled trials (RCTs) were included for analysis. The incidence of CR in NSCLC patients treated with ICIs was 1.5% (95% CI: 0.8-3.0) compared to 0.7% (95% CI: 0.4-1.2) in chemotherapy (CT) groups. The use of ICIs in advanced NSCLC significantly improved the possibility of archiving CR (RR 2.89, 95% CI: 1.44-5.81, P=0.003) compared to CT. Subgroup analysis according to ICIs showed that the use of atezolizumab (RR 3.26, P=0.01) and nivolumab (RR 4.83, P=0.042) in advanced NSCLC significantly improved the CR rate in comparison with CT alone, but not pembrolizumab and ipilimumab. We also found that the use of ICIs as first-line (RR 2.39, 95% CI: 1.08-5.3, P=0.032) or second-line (RR 4.99, 95% CI: 1.10-22.66, P=0.038) therapy significantly increased the change in obtaining a CR. In addition, correlation analysis indicates that PFS was strongly correlated with OS in NSCLC patients who received ICIs (r=0.89 for PFS, P=0.017). No marked correlation was found between OS and CR (r=0.19, P=0.75) and OS and ORR (r=0.52, P=0.28). Conclusion: The CR is a rate event in advanced NSCLC, but the use of ICIs significantly increases the possibility of archiving CR in comparison with CT. PFS is significantly correlated with OS and could be used as a surrogate end point, but not for CRs and ORRs.

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Management of Brain Metastases in the New Era of Checkpoint Inhibition

Cited by 32 publications

References 60 publications

Review: Brain Metastases in Bladder Cancer

Review: Brain Metastases in Bladder Cancer

Management of brain metastases: history and the present

<p>Complete response associated with immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis of nine randomized controlled trials</p>

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