Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer

Duan, Jianchun; Cui, Longgang; Zhao, Xiaochen; Bai, Hua; Cai, Shangli; Wang, Guoqiang; Zhao, Zhengyi; Zhao, Jing; Chen, Shiqing; Song, Jia; Qi, Chuang; Wang, Qing; Huang, Mengli; Zhang, Yuzi; Huang, Depei; Bai, Yuezong; Sun, Feng; Lee, John; Wang, Zhijie; Wang, Jie

doi:10.1001/jamaoncol.2019.5367

Cited by 257 publications

(238 citation statements)

References 62 publications

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“…In addition, although a previous mirror meta-analysis found that PD-1 inhibitors exhibited better survival outcomes than PD-L1 inhibitors in patients with solid tumors, 19 our meta-analysis demonstrated no significant differences between PD-1 and PD-L1 inhibitors plus chemotherapy for patients with ES-SCLC, in terms of ORR, PFS and OS. However, the findings were obtained from indirect analysis.…”

Section: Discussioncontrasting

confidence: 82%

Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer

Zhou

Zhao

Gong

et al. 2020

J Immunother Cancer

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We performed a meta-analysis to comprehensively investigate the efficacy and safety of immune-checkpoint inhibitors (ICIs) plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and ≥grade 3 adverse events (AEs). A total of six studies involving 2905 patients were identified, including 469 patients receiving program death ligand 1 (PD-L1) inhibitor plus chemotherapy, 308 receiving PD-1 inhibitors plus chemotherapy, 563 receiving CTLA-4 inhibitors plus chemotherapy, 268 receiving PD-L1/CTLA-4 inhibitors plus chemotherapy, and 1297 receiving chemotherapy alone. 10.8% (283/2615) patients had baseline brain metastases (BMs). Notably, ICIs plus chemotherapy was associated with significantly improved OS (HR, 0.82; 95% CI, 0.75 to 0.89). Subgroup analyses revealed that PD-1 inhibitors (HR, 0.77; 95% CI, 0.64 to 0.92) and PD-L1 inhibitors (HR, 0.73; 95% CI, 0.63 to 0.85) plus chemotherapy yielded a statistically significant improvement in OS while CTLA-4 inhibitors did not (HR, 0.92; 95% CI, 0.81 to 1.06). In patients with baseline BMs, ICIs plus chemotherapy showed no survival benefits over chemotherapy alone (HR, 1.23; 95% CI, 0.92 to 1.64). ICIs plus chemotherapy also significantly prolonged PFS (HR, 0.81; 95% CI, 0.75 to 0.87) while the pooled ORRs were comparable between ICIs plus chemotherapy and chemotherapy alone (RR, 1.04; 95% CI, 0.99 to 1.10). Patients treated with CTLA-4 inhibitors (relative risk (RR), 1.12; 95% CI, 0.99 to 1.28) experienced more≥grade 3 AEs than those treated with PD-1/PD-L1 inhibitors (RR, 1.03; 95% CI, 0.96 to 1.11). The addition of PD-1/PD-L1 inhibitors to chemotherapy resulted in significant improvements in both PFS and OS for patients with treatment-naïve ES-SCLC, not at the cost of increased AEs.

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Section: Discussioncontrasting

confidence: 82%

Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer

Zhou

Zhao

Gong

et al. 2020

J Immunother Cancer

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“…Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1), its ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), including nivolumab, atezolizumab, and ipilimumab etc., have been increasingly applied in treating several kinds of cancers because of their evident efficacy [1,2]. Although the use of ICIs has brought survival benefits to cancer patients, the efficacy of ICIs varies widely among cancer patients during clinical practice with some patients experiencing a poor prognosis because of ICIs resistance [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Wu²,

Wang

et al. 2020

J Transl Med

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Background: Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy. Methods: A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate the influence of BMI on ICIs efficacy. Pooled analysis for overall survival (OS), progression-free survival (PFS) and immunerelated adverse effects (IRAEs) were analyzed in current study. Results: A total of 13 eligible studies comprising 5279 cancer patients treated with ICIs were included in the analysis. The pooled analysis showed there is positive association between high BMI and improved OS and PFS among patients with ICIs treatment (OS: HR = 0.62, 95% CI 0.55-0.71, P < 0.0001; I 2 = 26.3%, P = 0.202); PFS: HR = 0.71, 95% CI 0.61-0.83, P < 0.0001; I 2 = 0%, P = 0.591). There is no significant difference between the incidence of all grade IRAEs between obese, overweight patients and normal patients (Overweight vs Normal: pooled RR = 1.28, 95% CI 0.76-2.18, P = 0.356; Obese vs Normal: pooled RR = 1.36, 95% CI 0.85-2.17, P = 0.207). Conclusion: An improved OS and PFS were observed in patients with high BMI after receiving ICIs treatment compared with patients of low BMI. No significant association between BMI and incidence of IRAEs was found in cancer patients after ICIs treatment.

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“…In this decade, many reported clinical trials for immunotherapy in various solid cancer types, including earlier challenging cancers, revealed an increase in OS and considerable strength in the treatment of NSCLC, in either combination or monotherapy (12,13). The present study, which is a populationbased study that used the SEER database, reveals good survival benefits in advanced NSCLC, which were largely attributable to the introduction of immunotherapeutic drugs to therapeutic regimens.…”

Section: Discussionmentioning

confidence: 50%

Overall Survival in Heart Disease–Related Death in Non-Small Cell Lung Cancer Patients: Nonimmunotherapy Versus Immunotherapy Era: Population-Based Study

et al. 2020

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The cardiotoxicity during immunotherapy administration leads to mortality by more than 42% and heart disease-related mortality among immunotherapy-linked cancers is still considered to be underestimated. In this study, the advanced stage of non-small cell lung cancer (NSCLC) with heart disease-related death was selected in accordance with immunotherapy approval time. NSCLC was searched on the Surveillance, Epidemiology, and End Results (SEER) program. Results show that 538 advanced NSCLC cases, those dominated by men and elderly people aged more than 70 years, had a high percentage of heart disease-related death in both eras. The difference between contemporary groups was fairly nonsignificant (P = > 0.05). The overall survival (OS) of allcause mortality difference showed improved survival in the immunotherapy group (P = 0.0001). In the study of heart disease-related death survival with adjusted data, the NSCLC patients show significant lower survival in the immunotherapy era compared with the nonimmunotherapy era (P = 0.003; hazard ratio [HR] = 1.31; 95% CI = 1.099-1.57). In the multivariate analysis of NSCLC-related immunotherapy, histology revealed that the non-squamous cell type had an independent risk for lower OS than the squamous cell type (P = 0.04; HR= 0.74; CI = 0, 55-0.99). The results demonstrate the survival benefits for NSCLC in immunotherapy; however, in heart disease-related death, immunotherapy in patients with NSCLC shows decreased OS. This study highlights that NSCLC patients should be highly monitored during immunotherapy administration, and further assessment is needed.

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Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer

Cited by 257 publications

References 62 publications

Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer

Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer

Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Overall Survival in Heart Disease–Related Death in Non-Small Cell Lung Cancer Patients: Nonimmunotherapy Versus Immunotherapy Era: Population-Based Study

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