Outcomes targeting the PD-1/PD-L1 axis in conjunction with stereotactic radiation for patients with non-small cell lung cancer brain metastases

Abstract

Anti-PD-1/PD-L1 therapies have demonstrated activity in patients with advanced stage non-small cell lung cancer (NSCLC). However, little is known about the safety and feasibility of patients receiving anti-PD-1/PD-L1 therapy and stereotactic radiation for the treatment of brain metastases. Data were analyzed retrospectively from NSCLC patients treated with stereotactic radiation either before, during or after anti-PD-1/PD-L1 therapy with nivolumab (anti-PD-1) or durvalumab (anti-PD-L1). Seventeen patients treated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiation therapy (FSRT) to 49 brain metastases over 21 sessions were identified. Radiation was administered prior to, during and after anti-PD-1/PD-L1 therapy in 22 lesions (45%), 13 lesions (27%), and 14 lesions (29%), respectively. The 6 months Kaplan-Meier (KM) distant brain control rate was 48% following stereotactic radiation. Six and 12 month KM rates of OS from the date of stereotactic radiation and the date of cranial metastases diagnosis were 48/41% and 81/51%, respectively. The 6 month rate of distant brain control following stereotactic radiation for patients treated with stereotactic radiation during or prior to anti-PD-1/PD-L1 therapy was 57% compared to 0% among patients who received anti-PD-1/PD-L1 therapy before stereotactic radiation (p = 0.05). A Karnofsky Performance Status (KPS) of <90 was found to be predictive of worse OS following radiation treatment on both univariate and multivariate analyses (MVA, p = 0.01). In our series, stereotactic radiation to NSCLC brain metastases was well tolerated in patients who received anti-PD-1/PD-L1 therapy. Prospective evaluation to determine how these two modalities can be used synergistically to improve distant brain control and OS is warranted.

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

“…Studies have found that radiotherapy promotes the release of various factors in tumors and surrounding tissues, leading to immunogenic death of tumor cells, activating APCs, releasing various cytokines, activating T cells, and promoting the immune system to attack tumor cells. 66 A previous retrospective study 67 included 17 cases treated with PD-1/PD-L1 inhibitors and stereotactic radiotherapy therapy for NSCLC patients, starting from the radiation of OS 5.6 months, starting from the diagnosis of OS 17.9 months. PD-1/PD-L1 antibodies before or patients with stereotactic radiosurgery (SRS) in the treatment and after treatment for six months in patients with intracranial ORR of SRS were 57% and 0%, respectively.…”

Non-small cell lung cancer brain metastases and the immune system: From brain metastases development to treatment

“…In general, PD-L1 positive patients have a higher chance for a better [69][70][71][72][73][74][75][76][77][78][79] outcome with anti-PD-(L)1 treatment compared to PD-L1 negative patients [47][48][49]. BM seem to present a clonal population of cells distinct from those in the primary site with somatic mutations that may be driven by the brain microenvironment [50].…”

“…However, these are probably different patient populations, the ones treated with radiation after ICI seeming the ones with the worst prognosis as they already progressed on ICI. The earliest retrospective data on the outcomes of ICI in conjunction with SRT for patients with NSCLC BM included 17 patients treated with durvalumab or nivolumab [79]. MRI imaging was performed at 2-3 months intervals and BM failure was defined by iRANO.…”

Quantification of Scheduling Impact on Safety and Efficacy Outcomes of Brain Metastasis Radio- and Immuno-Therapies: A Systematic Review and Meta-Analysis

“…Since median OS or PFS were reported without CIs in the majority of studies, we based our analysis on milestone OS measures, thus only studies reporting such measures were included into the final analysis dataset. For similar reasons, objective response rate (ORR) data were not included into the final dataset, since this measure was reported in only 8 studies, moreover with different response criteria used across these, including response evaluation criteria in solid tumors (RECIST) ( 26 ), criteria proposed by the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) working group ( 21 , 27 ) and World Health Organization (WHO) ( 28 ), and immune-related response criteria (irRC) ( 26 , 28 – 30 ). Information on distant intracranial control was not included either, since it was reported in 8 studies only and measured using different methods, making these data not suitable for data pooling.…”