Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Ceppi, Marcello; Bruzzone, Marco; Taveggia, Paola; Cavo, Alessia; Scordamaglia, Francesca; Gualco, Marina; Filiberti, Rosa Angela

doi:10.3390/cancers13061388

Cited by 30 publications

(26 citation statements)

References 65 publications

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“…In recent years, the use of ICIs for the treatment of NSCLC has considerably increased. Monoclonal antibodies that target the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis have been approved as first-and second-line treatments for advanced NSCLC worldwide (12). So far, several clinical trials have reported the efficacy and safety of neoadjuvant immunotherapy (13)(14)(15)(16)(17)(18) or chemoimmunotherapy (19)(20)(21)(22)(23)(24)(25)(26)(27)(28) in stages I-III NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer: a systematic review and meta-analysis

Jiang¹,

Wang²,

Gao³

et al. 2022

Transl Lung Cancer Res

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Background: In recent years, a series of clinical trials have explored the application of neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemoimmunotherapy have yet been reported.This study aimed to summarize and compare the efficacy and safety of neoadjuvant immunotherapy and chemoimmunotherapy in NSCLC.Methods: Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in NSCLC published before June 2021 was retrieved from PubMed, Embase, and the Cochrane Library. Study endpoints included major pathological response (MPR), complete pathological response (pCR), treatment-related adverse events (TRAEs), severe adverse events (SAEs), resection rate, surgical delay rate, and conversion to thoracotomy. The risk of bias was assessed using the Cochrane bias risk assessment tool. Subgroup and sensitivity analyses were further performed.Results: A total of 988 patients from 16 studies were included in this meta-analysis. For patients who received neoadjuvant immunotherapy with single/combined ICIs or chemoimmunotherapy, the pooled MPR rate was 43.5% and the pooled pCR rate was 21.9%. The pooled incidence of TRAEs and SAEs were 54.8% and 15.3%, respectively. The pooled resection rate was 85.8%, the surgical delay rate was 7.4%, and the conversion rate was 17.4%. Patients who received neoadjuvant chemoimmunotherapy had remarkably improved pathological response (MPR rate: 53.3% vs. 28.6%; pCR rate: 28.6% vs. 9.9%) compared with those receiving neoadjuvant single-agent immunotherapy, while the incidence of SAEs (18.0% vs. 12.3%) and surgical delay rate (3.8% vs. 7.4%) did not significantly increase. Neoadjuvant nivolumab combined with ipilimumab also achieved a high pCR rate (28.6%) with tolerable toxicity. Nivolumab-and pembrolizumabbased neoadjuvant therapy showed a higher MPR rate (nivolumab 51.5%, pembrolizumab 46.8%) and pCR rate (nivolumab 29.1%, pembrolizumab 31.5%). Besides, patients with positive programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) ≥1%] exhibited favorable pathological responses than PD-L1 negative patients.Discussion: Overall, neoadjuvant immunotherapy or chemoimmunotherapy is effective and safe in NSCLC. Compared with single-agent immunotherapy, neoadjuvant chemoimmunotherapy provides a significant improvement in pathological response without increasing the incidence of SAEs or surgical delay.These results need further confirmation by more large-scale randomized controlled trials.

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Section: Introductionmentioning

confidence: 99%

Neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer: a systematic review and meta-analysis

Jiang¹,

Wang²,

Gao³

et al. 2022

Transl Lung Cancer Res

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“…While other MAs have evaluated the efficacy and/or safety of anti-PD-L1-containing strategies [ 7 , 8 , 9 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], to date this is the first safety MA to include studies evaluating first-line single immunotherapy agents in NSCLC patients with a PD-L1 positive expression enriched design.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, anti-PD-L1 monotherapy resulted in significantly longer overall survival and progression free survival in advanced NSCLC patients with high PD-L1 expression compared to chemotherapy alone, thus supporting the potential of this therapeutic option as a first-line strategy for this subgroup of patients [ 9 ]. In the past few years, several studies have focused on the efficacy and safety of PD-1/PD-L1 inhibitor agent immunotherapies [ 7 , 8 , 9 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. However, no safety comparisons evaluating first-line monotherapy with anti-PD-L1 agents in NSCLC patients with a PD-L1 positive expression enriched design have been published to date.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis

Campelo

Arriola

Campos-Balea

et al. 2021

JCM

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This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

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“…And in real-world head-to-head comparison in metastatic melanoma for frontline therapy, efficacy of nivolumab was similar to that of pembrolizumab and no significant difference in OS was observed ( Moser et al, 2020 ). Furthermore, a meta-analysis that enrolled 32 studies of daily clinical practice demonstrated anti-PD-1 and anti-PD-L1 immunotherapy provided survival benefits as sconed-line treatment of NSCLC, in which the median PFS and OS were 3.35 and 9.98 months, respectively ( Mencoboni et al, 2021 ). Although most patients enrolled in this meta-analysis were treated with nivolumab, the efficacy in clinical practice is comparable to that in clinical trials.…”

Section: Clinical Use Efficacy and Safetymentioning

confidence: 99%

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

2021

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Over the past decade, diverse PD-1/PD-L1 blockades have demonstrated significant clinical benefit in across a wide range of tumor and cancer types. With the increasing number of PD-1/PD-L1 blockades available in the market, differences between the clinical performance of each of them started to be reported. Here, we provide a comprehensive historical and biological perspective regarding the underlying mechanism and clinical performance of PD-1/PD-L1 blockades, with an emphasis on the comparisons of their clinical efficacy and safety. The real-world evidence indicated that PD-1 blockade may be more effective than the PD-L1, though no significant differences were found as regards to their safety profiles. Future head-to-head studies are warranted for direct comparison between them. Finally, we summarize the yet to be elucidated questions and future promise of anti-PD-1/PD-L1 immunotherapy, including a need to explore novel biomarkers, novel combinatorial strategies, and their clinical use on chronic infection.

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Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cited by 30 publications

References 65 publications

Neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer: a systematic review and meta-analysis

Neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer: a systematic review and meta-analysis

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis

Comparisons of Underlying Mechanisms, Clinical Efficacy and Safety Between Anti-PD-1 and Anti-PD-L1 Immunotherapy: The State-of-the-Art Review and Future Perspectives

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