The efficacy and safety of combination therapy with immune checkpoint inhibitors in non-small cell lung cancer: A meta-analysis

Mo, Dun-Chang; Huang, Jianfeng; Luo, Peng-Hui; Huang, Shang-Xiao; Wang, Han-Lei

doi:10.1016/j.intimp.2021.107594

“…Compared with the study of Mo et al, 39 which mainly compared ICIs plus chemotherapy versus chemotherapy, we focused on performing the comparison of two mainstream ICIs (CP) targeting different signalling pathways versus chemotherapy or single ICI (P), and this is the first meta‐analysis comparing CP versus chemotherapy or P. We have consistent results showing that combination therapy can improve survival with manageable toxicity, but we also elucidated the time‐dependent effect of CP and the effect of PD‐L1 expression to better guide the use of ICIs for NSCLC patients. However, when interpreting our results, we should take several limitations into consideration.…”

Section: Resultsmentioning

confidence: 80%

The benefits and risks of CTLA4 inhibitor plus PD1/PDL1 inhibitor in stage IIIB/IV non‐small cell lung cancer: A systematic analysis and meta‐analysis based on randomized controlled trials

Liu

¹

,

Fang

²

,

Liu

³

et al. 2021

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What is known and objective Although immune checkpoint inhibitors (ICIs) have shown clinical benefit for patients with non‐small cell lung cancer (NSCLC), the efficacy of the combination of ICIs targeting different pathways is still unclear. We performed this meta‐analysis to explore the efficacy of cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) inhibitor plus programmed cell death 1 receptor (PD‐1)/programmed cell death receptor ligand 1 (PD‐L1) inhibitor therapy (CP) for NSCLC IIIB/IV patients. Methods We systematically searched the main databases for relevant studies. The main outcomes were overall survival (OS) and progression‐free survival (PFS). Results and discussion We identified 3526 articles, including 5 randomized controlled trials (RCTs) (4377 patients), in our meta‐analysis. We conducted two comparisons of CP versus chemotherapy or PD1/PDL1 inhibitor (P). Compared with chemotherapy, CP was more effective, with better OS (hazard ratio [HR]: 0.77, 95% CI [confidence interval]: 0.66–0.91; p = 0.001), better PFS (HR: 0.77, 95% CI: 0.70–0.85; p < 0.00001) and comparable objective response rate (ORR) (risk ratio [RR]: 1.27, 95% CI: 0.98–1.65; p = 0.07); in terms of toxicity, CP was comparable to chemotherapy across all‐grade adverse events (AEs) (RR: 0.87, 95% CI: 0.73–1.03; p = 0.11) and grade 3–5 AEs (RR: 0.85, 95% CI: 0.63–1.14; p = 0.27). Compared with P, CP had no superiority in efficacy in terms of the OS (HR: 1.04, 95%CI: 0.86–1.24; p=0.70), PFS (HR: 0.95, 95%CI: 0.75–1.22; p = 0.70) and the ORR (RR: 1.07, 95% CI: 0.95–1.21; p = 0.27) but CP was more effective than P when PD‐L1 expression was <1% (RR: 0.77,95%CI: 0.60–0.98; p = 0.04); in terms of toxicity, CP was associated with increased all‐grade AEs (RR:1.07, 95% CI: 0.97–1.19; p = 0.18) and grade 3–5 AEs (RR:1.58, 95% CI: 1.21–2.07; p = 0.0008). What is new and conclusion CP is a beneficial therapeutic schedule with longer PFS and OS than chemotherapy and has an acceptable, manageable grade 3–4 AE rate in IIIB/IV NSCLC. However, compared with P, CP results in better OS only in patients with PD‐L1 expression <1%.

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“…In NSCLC, a meta-analysis showed that immunotherapy combined with other treatments (e.g. chemotherapy, targeted therapy, double agent immunotherapy) significantly improved OS (HR = 0.74, 95% CI: 0.63-0.85, p = 0.001), PFS (HR = 0.74, 95% CI: 0.63-0.85, p = 0.001), and ORR (OR = 1.51, 95% CI: 1.02-2.00, p < 0.001) (19).…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

He

¹

,

Xu

²

,

Li

³

et al. 2021

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Thyroid Hürthle cell carcinoma, known as thyroid eosinophilic carcinoma, is a rare pathological type of differentiated thyroid cancer (DTC), representing 3-4% of all thyroid cancers. However, given the high risk of invasion and metastasis, thyroid Hürthle cell carcinoma has a relatively poor prognosis. Traditional treatment methods have limited effects on patients with metastatic thyroid cancers. Developing a valuable therapy for advanced thyroid carcinomas is an unfilled need, and immunotherapy could represent another choice for these tumors. We herein reported the case of a patient with recurrent advanced thyroid Hürthle cell cancer and positive programmed death-ligand 1 (PD-L1) expression, who suffered tumor progression after re-surgery, radiotherapy, and targeted therapy. It is encouraging that PD-1 inhibitors in combination with GM-CSF and stereotactic body irradiation (SBRT) on metastatic disease have a significant anti-tumor effect.

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“…Recently, a few meta-analyses [54][55][56] on the topic of ICI combination strategy have been published. Te study of Mo et al [54] included nine RCTs and compared the PFS and OS benefts from the combination therapy, such as immunotherapy plus chemotherapy, double immunotherapy agents, or immunotherapy plus targeted chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a few meta-analyses [54][55][56] on the topic of ICI combination strategy have been published. Te study of Mo et al [54] included nine RCTs and compared the PFS and OS benefts from the combination therapy, such as immunotherapy plus chemotherapy, double immunotherapy agents, or immunotherapy plus targeted chemotherapy. Te results of their study provided a clear suggestion that the risks of death and disease progression were signifcantly reduced when immunotherapy was combined with chemotherapy or other treatment options in NSCLC patients [54].…”

Section: Discussionmentioning

confidence: 99%

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis

Xu

¹

,

Cao

²

,

Zhou

³

et al. 2023

Journal of Oncology

1

0

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Objective. Recent evidence suggests that combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) may result in better outcomes. In this study, we assessed the efficacy and safety of ICI plus radiation versus ICI alone and explored potential factors affecting its efficacy in advanced non-small-cell lung cancer (NSCLC) patients. Methods. The databases including PubMed and Embase were searched to retrieve eligible studies comparing the efficacy and safety outcomes in advanced NSCLC patients after ICIs ± RT treatments. We performed subgroup analyses to identify potential prognostic factors from radiation details and study types. The odds ratio (OR) of objective response rate (ORR) and disease control rate (DCR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS), and risk ratio (RR) of adverse events were used to represent the outcome effects. Results. 26 eligible studies with 14192 cases were included. The results showed that the ORR (OR = 0.63, 95% CI: 0.42, 0.93; p = 0.02) and DCR (OR = 0.55, 95% CI: 0.36, 0.82; p < 0.01) of RT + ICIs groups were significantly higher than those of the ICIs alone group. The median PFS and OS for ICIs versus RT + ICIs were 2.2 versus 4.4 months and 9.0 versus 13.4 months, respectively. Patients in the ICIs plus RT group had a significantly better PFS (HR = 0.72, 95% CI: 0.64, 0.81; p < 0.01) and OS (HR = 0.74, 95% CI: 0.65, 0.83; p < 0.01) when compared to those in the ICIs group. In terms of adverse events, the risk of pneumonia was not significantly increased in patients treated with both ICIs and RT when compared to ICIs group alone (risk ratio = 0.89; 95% CI: 0.55, 1.44; p = 0.63). The correlation analysis found that PFS was significantly correlated with OS (p = 0.02). The subgroup analysis results showed that significant improvements in OS were observed in non-palliative RT group (HR = 0.29, 95% CI: 0.13, 0.65; p < 0.01) and extracranial RT group (HR = 0.70, 95% CI: 0.59, 0.83; p < 0.01). RT type could also be a prognostic factor associated with the OS (for conventional RT: HR = 0.68 and p = 0.22; for stereotactic body radiation therapy: HR = 0.77 and p < 0.01). However, concerning RT timing, the results showed a similar trend in reducing mortality risk (for previous RT: HR = 0.64 and p = 0.21; for concurrent RT: HR = 0.35 and p = 0.16). Conclusion. RT plus ICIs is associated with improved survival for advanced NSCLC patients, especially for those with non-palliative RT. Further clinical trials are needed to validate its effect on survival outcomes.

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The efficacy and safety of combination therapy with immune checkpoint inhibitors in non-small cell lung cancer: A meta-analysis

Cited by 15 publications

References 42 publications

The benefits and risks of CTLA4 inhibitor plus PD1/PDL1 inhibitor in stage IIIB/IV non‐small cell lung cancer: A systematic analysis and meta‐analysis based on randomized controlled trials

The benefits and risks of CTLA4 inhibitor plus PD1/PDL1 inhibitor in stage IIIB/IV non‐small cell lung cancer: A systematic analysis and meta‐analysis based on randomized controlled trials

Anti-PD-1 Immunotherapy Combined With Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient With Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Review

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients: A Systematic Review and Meta-Analysis

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