Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Tozuka T

PROVIDER: S-EPMC7471023 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Tozuka Takehiro T Kitazono Satoru S Sakamoto Hiroaki H Yoshida Hiroshi H Amino Yoshiaki Y Uematsu Shinya S Yoshizawa Takahiro T Hasegawa Tsukasa T Ariyasu Ryo R Uchibori Ken K Yanagitani Noriko N Horai Takeshi T Seike Masahiro M Gemma Akihiko A Nishio Makoto M

Thoracic cancer 20200712 9

<h4>Background</h4>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.<h4>Methods</h4>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. Pati ...[more]

PMID: 32657011

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Project description:ImportanceDespite the efficacy of immune checkpoint inhibitors (ICIs), cutaneous immune-related adverse events (cirAEs) occur in 20% to 40% of all treated patients. To our knowledge, little is known about the predictive value of these cutaneous eruptions and their subtypes regarding cancer survival.ObjectiveTo determine the association of developing cirAEs following treatment with anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) therapy with patient survival.Design, setting, and participantsThis retrospective cohort study used data from the TriNetX Diamond Network, a database of health records and claims data from more than 200 million US and European patients, to conduct a population-level cohort analysis. The study included 7008 eligible patients who developed cirAEs after treatment with anti-PD-1 or anti-PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract who were identified through the TriNetX Diamond Network along with 7008 matched controls.ExposuresDevelopment of cirAEs within 6 months following anti-PD-1 or anti-PD-L1 therapy.Main outcomes and measuresA 6-month analysis using a Cox proportional hazards model was performed to determine the association of cirAEs with overall survival after adjusting for demographic characteristics, cancer type, and cancer stage.ResultsA total of 7008 patients (3036 women [43.3%]; mean [SD] age, 68.2 [11.2] years) were matched to 7008 (3044 women [43.4%]; mean [SD] age, 68.3 [11.1] years) controls. Pruritus (hazard ratio [HR], 0.695; 95% CI, 0.602-0.803; P < .001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897; P = .001), xerosis (HR, 0.626; 95% CI, 0.469-0.834; P = .001), nonspecific rashes (HR, 0.704; 95% CI, 0.634-0.781; P < .001), and appearance of any cirAE (HR, 0.778; 95% CI, 0.726-0.834; P < .001) were significantly protective of mortality using a Benjamini-Hochberg correction with a significance level of .05. Additionally, psoriasis (HR, 0.703; 95% CI, 0.497-0.994; P = .045) and lichen planus/lichenoid dermatitis (HR, 0.511; 95% CI, 0.279-0.939; P = .03) were significant. Eczematous dermatitis (HR, 0.612; 95% CI, 0.314-1.195), vitiligo (HR, 0.534; 95% CI, 0.254-1.123), bullous pemphigoid (HR, 0.524; 95% CI, 0.140-1.956), and Grover disease (HR, 0.468; 95% CI, 0.115-1.898) were all associated with strong protective clinical effects.Conclusions and relevanceThe results of this cohort study suggest that the development of cirAEs is strongly associated with response to ICI therapy and patient survival.

Project description:IntroductionProgrammed cell death-1/programmed cell death ligand-1 (PD-1/PDL-1) inhibitors are the newest class of approved drugs for advanced urothelial cancer (AdUC). This review aims to collate the evidence for their efficacy and safety in various treatment settings.MethodsExtensive search of databases was performed (updated May 2018) and the protocol was registered on PROSPERO (CRD42017081568). The review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement. STATA (v 12) and Revman 5.3.5 were used for data analysis.ResultsTen nonrandomized, open-label clinical trials were included in this review. PD-1/PD-L1 inhibitors were used as second-line, stand-alone in eight trials and as first-line in cisplatin-ineligible in two trials. Heterogeneity was observed for study design, PDL-1 testing methods, cutoff criterias used and translational markers evaluated. The pooled objective response rate (ORR) was 18.2% (95% confidence interval [CI] 15.1-21.2, n = 1785) with PD-1/PDL-1 inhibitors in second-line settings as compared to 12.6% (95% CI 10.3-14.9, n = 736) with second-line chemotherapy and 23.7% (95% CI 19.9-27.4, n = 489) with PD-1/PDL-1 inhibitors as first-line therapy in cisplatin-ineligible patients. The median progression-free survival and overall survival was similar with PD-1/PD-L1 inhibitors in both second- and first-line treatment settings (1.5-2.9 vs. 2.0-2.7 months and 7.9-18.2 vs. 15.9 months) and second-line chemotherapy (3.3-4.0 months and 7.4-8 months). Odds of achieving ORR was 0.10 (95% CI 0.03-0.31, n = 229) in the second-line, stand-alone setting with a combined positive score (CPS) cutoff of 25% and was 0.34 (95% CI 0.19-0.62, n = 265) with a CPS cut-off of 10% in first-line setting in the cisplatin-ineligible.ConclusionsPD-1/PDL-1 inhibitors appear to be promising in the treatment of AdUC and CPS may be a potentially reliable biomarker for predicting response but needs validation. Caution needs to be exercised until more data are available on imAEs and further studies are required to prove their worth as the standard of care.

Dataset Information

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

Background

Methods

Results

Conclusions

Key points

What this study adds

Publications

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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