Sally C M Lau1, Christopher Poletes2, Lisa W Le3, Kate M Mackay1, Aline Fusco Fares1, Penelope A Bradbury1, Frances A Shepherd1, Ming Sound Tsao4, Natasha B Leighl1, Geoffrey Liu1, David Shultz5, Adrian G Sacher6. 1. Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. 2. Department of Radiation Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. 3. Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. 4. Department of Pathology, Laboratory Medicine Program, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. 5. Department of Radiation Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. Electronic address: David.Shultz@rmp.uhn.ca. 6. Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address: Adrian.Sacher@uhn.ca.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) have excellent systemic activity and are standard first line treatment in EGFR/ALK wild type metastatic non-small cell lung cancer (NSCLC). However, their role in patients with brain metastases, which affects over 20% of patients and cause significant morbidity, is less clear. METHODS: We reviewed patients with EGFR/ALK wild-type mNSCLC with CNS metastases. Serial MRIs were reviewed to determine the time to intracranial progression (iPFS). Multivariate regression was performed to adjust for the disease-specific graded prognostic score (ds-GPA). RESULTS: We identified 36 ICI- and 33 chemotherapy-treated patients with baseline CNS metastases and available serial MRIs (average frequency:3.5 months). Baseline radiation was given except for 2 chemotherapy-treated patients with asymptomatic solitary metastasis. The CNS burden of disease was higher in the ICI-treated group (ICI:22% vs. chemotherapy:0% had >10 lesions; p = 0.02), but the utilization of WBRT was not (ICI:31% vs. chemotherapy:45%; p = 0.09). At the time of progression, CNS involvement was identified in 30 % of ICI-treated patients compared to 64 % of chemotherapy controls (p = 0.02). ICI-treated patients had superior iPFS (13.5 vs 8.4 months) that remained significant in multivariate analysis (HR 1.9; 95%CI 1.1--3.4). Superior CNS outcomes in ICI-treated patients were driven by the PD-L1 high subgroup where the 12-month cumulative incidence rate of CNS progression was 19% in ICI-treated PD-L1 ≥ 50%, 50% in ICI-treated PD-L1 < 50% and 58% in chemotherapy-treated patients (p = 0.03). CONCLUSIONS: Remarkable CNS disease control is seen with baseline RT plus ICIs in patients with PD-L1 ≥ 50%. Strategies for delaying WBRT should be investigated in this subgroup of patients.
BACKGROUND: Immune checkpoint inhibitors (ICIs) have excellent systemic activity and are standard first line treatment in EGFR/ALK wild type metastatic non-small cell lung cancer (NSCLC). However, their role in patients with brain metastases, which affects over 20% of patients and cause significant morbidity, is less clear. METHODS: We reviewed patients with EGFR/ALK wild-type mNSCLC with CNS metastases. Serial MRIs were reviewed to determine the time to intracranial progression (iPFS). Multivariate regression was performed to adjust for the disease-specific graded prognostic score (ds-GPA). RESULTS: We identified 36 ICI- and 33 chemotherapy-treated patients with baseline CNS metastases and available serial MRIs (average frequency:3.5 months). Baseline radiation was given except for 2 chemotherapy-treated patients with asymptomatic solitary metastasis. The CNS burden of disease was higher in the ICI-treated group (ICI:22% vs. chemotherapy:0% had >10 lesions; p = 0.02), but the utilization of WBRT was not (ICI:31% vs. chemotherapy:45%; p = 0.09). At the time of progression, CNS involvement was identified in 30 % of ICI-treated patients compared to 64 % of chemotherapy controls (p = 0.02). ICI-treated patients had superior iPFS (13.5 vs 8.4 months) that remained significant in multivariate analysis (HR 1.9; 95%CI 1.1--3.4). Superior CNS outcomes in ICI-treated patients were driven by the PD-L1 high subgroup where the 12-month cumulative incidence rate of CNS progression was 19% in ICI-treated PD-L1 ≥ 50%, 50% in ICI-treated PD-L1 < 50% and 58% in chemotherapy-treated patients (p = 0.03). CONCLUSIONS: Remarkable CNS disease control is seen with baseline RT plus ICIs in patients with PD-L1 ≥ 50%. Strategies for delaying WBRT should be investigated in this subgroup of patients.
Authors: Zhengfei Zhu; Jianjiao Ni; Xuwei Cai; Shengfa Su; Hongqing Zhuang; Zhenzhou Yang; Ming Chen; Shenglin Ma; Conghua Xie; Yaping Xu; Jiancheng Li; Hong Ge; Anwen Liu; Lujun Zhao; Chuangzhou Rao; Congying Xie; Nan Bi; Zhouguang Hui; Guangying Zhu; Zhiyong Yuan; Jun Wang; Lina Zhao; Wei Zhou; Chai Hong Rim; Arturo Navarro-Martin; Ben G L Vanneste; Dirk De Ruysscher; J Isabelle Choi; Jacek Jassem; Joe Y Chang; Lucyna Kepka; Lukas Käsmann; Michael T Milano; Paul Van Houtte; Rafal Suwinski; Alberto Traverso; Hiroshi Doi; Yang-Gun Suh; Georges Noël; Natsuo Tomita; Roman O Kowalchuk; Terence T Sio; Baosheng Li; Bing Lu; Xiaolong Fu Journal: Transl Lung Cancer Res Date: 2022-09