Outcome of Patients with Non–Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors

Hendriks, Lizza; Hénon, Clémence; Auclin, Édouard; Mezquita, Laura; Ferrara, Roberto; Audigier-Valette, Clarisse; Mazières, Julien; Lefèbvre, Caroline; Rabeau, Audrey; Moulec, Sylvestre Le; Cousin, Sophie; Duchemann, Boris; Péchoux, C. Le; Botticella, Angela; Ammari, Samy; Gazzah, Anas; Caramella, Caroline; Adam, Julien; Lechapt‐Zalcman, Emmanuèle; Planchard, David; Ruysscher, Dirk De; Dingemans, Anne-Marie; Besse, Benjamin

doi:10.1016/j.jtho.2019.02.009

Cited by 187 publications

(174 citation statements)

References 43 publications

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“…In total, 346 potentially relevant citations were reviewed (Figure 1). Ultimately, 16 studies published from 2009 to 2019 that reported OS and/or PFS data were included in the final analysis [17,[19][20][21][22][27][28][29][30][31][32][33][34][35][36][37]. The total number of patients included was 4045 ranging from 45 to 1025 patients per study (median, 151).…”

Section: Resultsmentioning

confidence: 99%

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Petrelli

Signorelli

Ghidini

et al. 2020

Cancers

211

156

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Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

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Section: Resultsmentioning

confidence: 99%

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Petrelli

Signorelli

Ghidini

et al. 2020

Cancers

211

156

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“…Brain metastases are not confirmed as a negative prognostic factor because ICIs may cross the blood-brain barrier and induce disease response in selected patients [31]. Data from both retrospective series [36] and clinical trials showed good activity of ICIs as a single agent [37] or in combination with chemotherapy [38] in patients with brain metastases.…”

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

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Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

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“…Another study retrospectively investigated the prognostic impact of the presence of BMs in routine clinical care as well as clinical trials. 21 The cohort included 1025 NSCLC patients who had received anti PD-1/PD-L1 Ab with or without anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), and multivariate analysis included the following factors: age, smoking status, histology, number of organs with metastases, line of treatment, PS, use of corticosteroids, and the presence of BMs. The study showed that the presence of BMs was not a significant factor for PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

Poor efficacy of anti‐programmed cell death‐1/ligand 1 monotherapy for non‐small cell lung cancer patients with active brain metastases

et al. 2020

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Background The efficacy of anti‐programmed cell death‐1/ligand 1 antibody monotherapy (anti‐PD‐1/PD‐L1 monotherapy) in patients with active brain metastases (BMs) is not established. Here, we aimed to evaluate the efficacy of anti‐PD‐1/PD‐L1 monotherapy in non‐small cell lung cancer (NSCLC) patients with active BMs. Methods This retrospective study included NSCLC patients treated with second‐line or later‐line anti‐PD‐1/PD‐L1 monotherapy between December 2015 and August 2019. Patients were classified into those with or without active BMs, including symptomatic BMs requiring systemic steroids and untreated BMs. The progression‐free survival (PFS) and overall survival (OS) of the patients with and without active BMs were compared. Intracranial and extracranial tumor responses were evaluated in patients with active BMs. Results We analyzed 197 patients who had received anti‐PD‐1/PD‐L1 monotherapy. Among them, 24 had active BMs. Among those without active BMs, 145 had no BMs and 28 had treated asymptomatic BMs. The PFS and OS of patients with active BMs were significantly shorter than those of patients without active BMs (1.3 vs. 2.7 months; P < 0.001, and 4.5 vs. 16.3 months; P = 0.001 respectively). For patients with active BMs, the intracranial and extracranial response rates were 13.3% and 26.7%, respectively. On multivariate analysis, active BMs, poor performance status (PS), and EGFR/ALK positivity were significant factors associated with shorter PFS. Active BMs and poor PS were significant factors associated with shorter OS. Conclusions This study suggested that anti‐PD‐1/PD‐L1 monotherapy was not effective for NSCLC patients with active BMs. Further studies on immunotherapy are needed for patients with active BMs. Key points Significant findings of the study: The present study showed that anti‐PD‐1/PD‐L1 antibody monotherapy was not effective for non‐small cell lung cancer patients with active brain metastases. Intracranial and extracranial response rates were 13.3% and 26.7%, respectively. What this study adds: Further studies on immunotherapy are needed for patients with active BMs.

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Outcome of Patients with Non–Small Cell Lung Cancer and Brain Metastases Treated with Checkpoint Inhibitors

Cited by 187 publications

References 43 publications

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Poor efficacy of anti‐programmed cell death‐1/ligand 1 monotherapy for non‐small cell lung cancer patients with active brain metastases

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