The efficacy and safety of anti‐<scp>PD</scp>‐1/<scp>PD‐L</scp>1 antibodies combined with chemotherapy or <scp>CTLA</scp>4 antibody as a first‐line treatment for advanced lung cancer

Xu, Xiaoling; Huang, Zhiyu; Zheng, Lei; Fan, Yun

doi:10.1002/ijc.31252

Cited by 44 publications

(40 citation statements)

References 52 publications

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“…The third question is whether additional ICIs to the first‐line chemotherapy is necessary for patients with low or negative expression for PD‐L1. Previous studies have shown that the synergistic activity and acceptable safety profile could be observed by the combination of checkpoint inhibitors and chemotherapy in the first‐line treatment of advanced NSCLC . With the inclusion of two recent studies, our study drew consistent conclusion that compared with standard chemotherapy, the combination of chemotherapy and ICIs, regardless of atezolizumab or pembrolizumab could acquire significant benefits in mOS, OSR1y, mPFS, PFSR6m, PFSR1y, and ORR for PD‐L1 unselected patients in spite of higher incidence of grade ≥ 3 TRAEs.…”

Section: Discussionsupporting

confidence: 61%

“…Previous studies have shown that the synergistic activity and acceptable safety profile could be observed by the combination of checkpoint inhibitors and chemotherapy in the first-line treatment of advanced NSCLC. 28,29 With the inclusion of two recent studies, our study drew consistent conclusion that compared with standard chemotherapy, the combination of chemotherapy and ICIs, regardless of atezolizumab or pembrolizumab could acquire significant benefits in mOS, OSR1y, mPFS, PFSR6m, PFSR1y, and ORR for PD-L1 unselected patients in spite of higher incidence of grade ≥ 3 TRAEs. When stratified by PD-L1 expression, patients with negative PD-L1 expression can further benefit from combination therapy in mOS, mPFS, and ORR, regardless of atezolizumab or pembrolizumab.…”

Section: Discussionmentioning

confidence: 59%

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Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

Cao

Zhang

et al. 2019

Cancer Medicine

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Objective To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first‐line treatment of advanced nonsmall cell lung cancer (NSCLC). Methods This meta‐analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting abstracts. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression‐free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1‐year (PFSR1y), objective response rates (ORR), and treatment‐related adverse events (TRAEs). Results Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death‐ligand 1 (PD‐L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m ( P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD‐L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD‐L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD‐L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. Conclusions The findings support the rationale for using pembrolizumab alone in the first‐line treatment of PD‐L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD‐L1 ≤ 49% for significant survival benefit.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 59%

Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

Cao

Zhang

et al. 2019

Cancer Medicine

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“…The combined ORRs of I, C and I + C were 32, 32 and 50%, which illustrated that the population to receive benefit from PD‐1/L1 and chemotherapy might be different, while a combined strategy would not only prolong patients’ life expectancy but also benefit more people. Xu et al conducted a meta‐analysis based on the majority of phase I and II clinical trials, they observed significant improvement in PFS but not in OS of checkpoint inhibitors (PD‐1/L1 or CTLA‐4) with chemotherapy as a first‐line treatment compared to chemotherapy. We included the latest phase III international RCTs and also did the indirect comparison, with the purpose of reporting the efficacy and safety of PD‐1/L1 Inhibitors, chemotherapy and their combination in front‐line treatment of NSCLC according to PD‐L1 expression.…”

Section: Discussionmentioning

confidence: 99%

PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

Liang

Liu

Pan

et al. 2019

Intl Journal of Cancer

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We comprehensively compared the therapeutic effects and safety of PD-1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first-line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD-L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD-1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65-1.24) and OS (HR 0.84, 0.64-1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58-0.71) and OS (HR 0.74, 0.62-0.89). I + C also showed advantages over PD-1/L1 in PFS (HR 0.71, 0.51-0.99) but not OS (HR 0.88, 0.64-1.22). In the PD-L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67-0.90) and PFS (HR 0.72, 0.65-0.80) than chemotherapy. In PD-L1 ≥ 50% population, PD-1/L1 had longer OS than chemotherapy (HR 0.71, 0.60-0.84); I + C also had longer OS (HR 0.61, 0.49-0.77) and PFS (HR 0.41,0.34-0.49) than chemotherapy. In indirect analysis (PD-L1 ≥ 50%), I + C was superior to PD-1/L1 in terms of PFS (HR 0.54, 0.35-0.82), but not OS (HR 0.86,. Both treatment-related and immune-mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first-line treatment for NSCLC patients with different PD-L1 expression, in the meanwhile, in cautious of side effects.

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“…Previous studies reported synergistic treatment of anti-PD-1 and anti-CTLA-4 had high response rate and durable response with tolerable safety profile. 44,45 These exploratory investigations showed encouraging clinical activity and feasibility of combination therapies. New combinations of ICIs with classical chemotherapy and/or radiotherapy will further revolutionize the treatment of NSCLC.…”

Section: E1457600-4mentioning

confidence: 98%

Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer

et al. 2018

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Immune checkpoint inhibitors (ICIs) are new therapeutic strategies for non-small cell lung cancer (NSCLC). We aimed to quantitatively evaluate the efficacy and safety of ICIs in NSCLC. Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized clinical trials comparing ICIs with control therapies in NSCLC. Data were pooled according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A total of 12 trails comprising 6,919 NSCLC patients were included in this meta-analysis. ICIs therapies significantly improved progression-free survival (PFS) (HR, 0.838; < 0.001), overall survival (OS) (HR, 0.747; < 0.001) and objective response rates (ORR) (RR, 1.311; < 0.001) in NSCLC. Prognostic benefit was observed irrespective of age, sex, treatment line, performance status and histology. Survival improvement of ICIs was limited for NSCLC patients with non-smoker (PFS, = 0.468; OS, = 0.317) or central nervous system (CNS) metastasis (PFS, = 0.209; OS, = 0.090), or positive EGFR mutation (PFS, = 0.083; OS, = 0.522) or PD-L1 expression level less than 5% (PFS, = 0.370; OS, = 0.047). The relative risks of all-grade and high-grade (≥3) anemia, neutropenia, leukopenia, thrombocytopenia, stomatitis, nausea, pyrexia, asthenia and neuropathy were all decreased in patients received ICIs compared with control therapies. This meta-analysis provides clinical evidence that ICIs improve PFS, OS, and ORR in NSCLC with fewer adverse effects. Our data establish ICIs as a prefer treatment option for NSCLC patients with smoker, no CNS metastasis, wild type EGFR, and high PD-L1 expression.

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The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

Cited by 44 publications

References 52 publications

Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer

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