Efficacy and safety data from patients with advanced squamous NSCLC and brain metastases participating in the nivolumab Expanded Access Programme (EAP) in Italy

Bidoli, Paolo; Chiari, Rita; Catino, A.; Grossi, Francesco; Noberasco, Cristina; Gelsomino, Francesco; Gilli, Marina; Proto, Claudia; Parra, Héctor Soto; Migliorino, Maria Rita; Bonomi, Lucia; Tassinari, Davide; Frassoldati, Antonio; Albanese, Valeria; Fadda, Guido; Cognetti, F.; Galitiis, Federica De; Finocchiaro, Giovanna; Delmonte, Angelo

doi:10.1093/annonc/mdw383.28

Cited by 19 publications

(24 citation statements)

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“…In the Expanded Access Programme of nivolumab, advanced lung squamous cell carcinoma (SCC) (http:// abstracts.asco.org/214/AbstView_214_228899.html), and terminal non-squamous cell carcinoma (NSCLC) 35 were studied. In the study of pulmonary SCC, 371 patients in stage III/IV were enrolled, including 37 with asymptomatic brain metastases.…”

Section: Nivolumab Nsclcmentioning

confidence: 99%

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Wang

Xie

et al. 2020

OTT

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The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood-brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20-30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain surgery remain the mainstream, PD-1/PD-L1 inhibitors display potential decreased neurotoxic effects. To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs.

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Section: Nivolumab Nsclcmentioning

confidence: 99%

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Wang

Xie

et al. 2020

OTT

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“…Additional data supporting nivolumab for untreated brain metastases comes from an Italian expanded-access program of 372 patients with advanced squamous NSCLC, 38 of whom had asymptomatic brain metastases ( 22 ). The disease control rate was 47.3% in this cohort, comprising of one CR, six PRs and 11 patients with stable disease.…”

Section: Clinical Datamentioning

confidence: 99%

Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease

Kamath

Kumthekar

2018

Front. Oncol.

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While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need.

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“…and Dudnik et al . showed a similar result, indicating that nivolumab has intracranial activity in patients with NSCLC and untreated/progressing brain metastases with low‐grade toxicity in general . In the latest clinical trials, Henon et al .…”

Section: Discussionmentioning

confidence: 65%

“…17 Studies conducted by Bidoli et al and Dudnik et al showed a similar result, indicating that nivolumab has intracranial activity in patients with NSCLC and untreated/progressing brain metastases with low-grade toxicity in general. 18,19 In the latest clinical trials, Henon et al evaluated 259 patients with NSCLC treated with ICIs. Among these, 48 (19%) had CNS involvement before immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for non‐small cell lung cancer with central nervous system metastases: A two‐case report

Zhang

2019

Thoracic Cancer

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Non‐small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. Central nervous system metastases are a common complication of NSCLC and confer a poor prognosis and a dismal survival rate. Treatment is limited, has poor outcomes, and affects patient quality of life. Pembrolizumab is an anti‐PD‐1 antibody that has shown good results for the management of NSCLC. However, its penetration of the central nervous system has not been well studied, and patients with untreated brain metastases are excluded from most clinical trials. Herein, we report two cases of NSCLC with brain metastases in patients successfully treated with pembrolizumab, and discuss the efficacy and safety of pembrolizumab in these patients. Pembrolizumab has shown good control and the patients have had long progression‐free survival with a high quality of life. Neither patient has experienced serious or grade 3–4 treatment‐related adverse events. Pembrolizumab demonstrates activity in brain metastases in NSCLC patients with an acceptable safety profile. Thus, there may be a role for systemic immunotherapy in patients with untreated or progressive brain metastases.

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Efficacy and safety data from patients with advanced squamous NSCLC and brain metastases participating in the nivolumab Expanded Access Programme (EAP) in Italy

Cited by 19 publications

References 0 publications

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease

Pembrolizumab for non‐small cell lung cancer with central nervous system metastases: A two‐case report

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