A meta-analysis on immune checkpoint inhibitor efficacy for advanced non-small cell lung cancer between East Asians versus non-East Asians

Peng, Siyu; Ying, Ariel Fangting; Tai, Bee Choo; Soo, Ross A.

doi:10.21037/tlcr-20-246

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…Given the analysis of subgroups, due to the small number of individuals analyzed, the results should be interpreted with caution. Individuals with advanced NSCLC of different regions have different clinical, genetic characteristics, and socioenvironmental make-up that may influence their response to PD-1 inhibitors ( 88 ). It is possible that there is some yet unknown mechanism that could explain the differences, or it is far more likely that this statistical significance is due to chance ( 89 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features

2022

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ObjectivePD-1 inhibitors have become an indispensable treatment in Non-Small Cell Lung Cancer (NSCLC), but the potential predictive value of clinical and molecular features need to be clarified. The objective of the study was to study the potency of PD-1 inhibitors in patients with NSCLC in contexts of both clinical and molecular features, and to aid identification of patients for choice of type of PD-1 inhibitor therapy in order to acquire more accurate NSCLC treatment in immunotherapy.MethodPubMed, Google Scholar, Embase Science Direct, the Cochrane library, and major oncology conferences were searched for randomized clinical trials (RCTs) that were published prior to December 2021. RCTs that had PD-1 inhibitor alone or in combination with chemotherapy with non-PD-1 inhibitor for the treatment of NSCLC patients were selected. Two authors independently selected studies, data extraction and bias risk assessment. Basic characteristics of included studies, and also the 95% confidence interval and hazard ratios of the overall patients and subgroups were recorded. The inverse variance weighted method was used to estimate pooled treatment data.ResultA total of eleven RCTs including 5,887 patients were involved. PD-1 inhibitors-based therapy substantially enhanced OS compared with non-PD-1 inhibitor therapy in patients with age group <65 years, 65–74 years, active or previous smokers, without brain metastases, liver metastases, EGFR wild-type patients, individuals in East Asia and U.S./Canada, but not in patients with age group ≥75 years, never smokers, brain metastases, EGFR mutant patients or individuals in Europe. OS was improved in patients with NSCLC who received PD-1 inhibitors regardless of their gender (male or female), histomorphological subtypes (squamous or non-squamous NSCLC), performance status (0 or 1), and PD-L1 tumor proportion score (TPS) (<1%, ≥1%, 1–49%, or ≥50%). An analysis of subgroups revealed that, patients with age group <65 years old, male, non squamous cell carcinoma, PS 1, TPS ≥1%, and TPS ≥50% benefited from pembrolizumab treatment not related with treatment line and treatment regimen.ConclusionAge group, smoking history, metastasis status/site, EGFR mutation status, and region can be used to predict the potency of PD-1 inhibitors, and to be individualized to choose different types of PD-1 inhibitors, and treatment regimen for NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features

2022

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“…Given the analysis of subgroups, the results should be interpreted with caution because of the small number of individuals analyzed. Individuals with advanced NSCLC of different races have different clinical and genetic characteristics and socio-environmental makeup, which may influence their response to atezolizumab ( 79 ). It is possible that there is some yet unknown mechanism that could explain these differences, or it is far more likely that this statistical significance is due to chance.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis

Liu

Huo²,

Chen³

2022

Front. Immunol.

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ObjectiveAtezolizumab is becoming a significant therapy for non-small cell lung cancer (NSCLC), but its efficacy needs to be further improved. The aims of this study are to clarify the potency of atezolizumab-based therapy in advanced NSCLC patients with different clinical and molecular features, and to choose a better therapeutic regimen of atezolizumab to achieve more precise treatment in immunotherapy.MethodsRandomized clinical trials (RCTs) in the Cochrane Library, PubMed, Embase Science Direct, and Google Scholar, together with major oncology conferences that compared atezolizumab with chemotherapy-based treatment for individuals with advanced NSCLC published prior to February 2022, were searched. Studies, bias risk assessment, and data extraction were selected by two independent authors. We extracted the basic features of the included studies, together with the 95% confidence interval (CI) and hazard ratios (HRs), from all patients and subgroups. The combined treatment data were assessed using the inverse variance weighting method.ResultsSeven RCTs including 4,859 patients were included. Our meta-analysis findings indicated that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77–0.88; p < 0.00001) and PFS (HR 0.72; 95% CI, 0.61–0.85; p < 0.0001) in patients with advanced NSCLC compared with chemotherapy-based treatment. Atezolizumab substantially enhanced OS in patients aged <65 years old and 65–74 years old, those with wild-type EGFR, those without liver metastases, active or previous smokers, white patients and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, and TC0 and IC0, but not in patients aged ≥75 years, never smokers, those with liver metastases, those with EGFR mutant, Asians, Black or African Americans, or those with TC1/2 or IC1/2. Patients with advanced NSCLC who received atezolizumab showed OS improvement regardless of sex (male or female), histological type (non-squamous or squamous NSCLC), performance status (0 or 1), and line of treatment (1st-line therapy or ≥2nd-line therapy). Subgroup analysis revealed that male individuals, those with non-squamous NSCLC, those with PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 achieved OS benefit from atezolizumab treatment not related to the treatment line and treatment regimen.ConclusionsAge group, smoking history, liver metastasis status, EGFR mutation status, race, and PD-L1 expression can be used to predict the potency of atezolizumab and provide a better treatment regimen for patients with advanced NSCLC to achieve accurate and personalized treatment.

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“…In the secondary analyses, the pooled Cox HR for PFS was 0.77, similar to prior estimations. 68 The pooled ST-HR, however, was 1.02—a signal to the oncologist suggesting possible harm with use of ICI therapy for disease control. In contrast, the pooled LT-DP for PFS was 0.10, indicating a 10% increment in long-term PFS probability for long-term survivors, compared with chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…In the primary analyses, we noted a pooled Cox HR for OS of 0.75—in line with prior ICI meta-analyses and consistent with the current understanding of survival benefit for approximately 20% to 40% of patients who receive ICI therapy. 67 , 68 With Cox-TEL deconvolution of patient subpopulations based on ICI treatment response, however, the pooled ST-HR was calculated as 0.86 and the pooled LT-DP as 0.08.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Cancer Survival Associated With Immune Checkpoint Inhibitors After Statistical Adjustment

et al. 2022

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ImportanceAppropriate clinical decision-making relies on accurate data interpretation, which in turn relies on the use of suitable statistical models. Long tails and early crossover—2 features commonly observed in immune checkpoint inhibitor (ICI) survival curves—raise questions as to the suitability of Cox proportional hazards regression for ICI survival analysis. Cox proportional hazards–Taylor expansion adjustment for long-term survival data (Cox-TEL) adjustment may provide possible solutions in this setting.ObjectiveTo estimate overall survival and progression-free survival benefits of ICI therapy vs chemotherapy using Cox-TEL adjustment.Data SourcesA PubMed search was performed for all cataloged publications through May 22, 2022.Study SelectionThe search was restricted to randomized clinical trials with search terms for ICIs and lung cancer, melanoma, or urothelial carcinoma. The publications identified were further reviewed for inclusion.Data Extraction and SynthesisCox proportional hazards ratios (HRs) were transformed to Cox-TEL HRs for patients with short-term treatment response (ie, short-term survivor) (ST-HR) and difference in proportions for patients with long-term survival (LT-DP) by Cox-TEL. Meta-analyses were performed using a frequentist random-effects model.Main Outcomes and MeasuresOutcomes of interest were pooled overall survival (primary outcome) and progression-free survival (secondary outcome) HRs, ST-HRs, and LT-DPs. Subgroup analyses stratified by cancer type also were performed.ResultsA total of 1036 publications was identified. After 3 levels of review against inclusion criteria, 13 clinical trials (7 in non–small cell lung cancer, 3 in melanoma, and 3 in urothelial carcinoma) were selected for the meta-analysis. In the primary analysis, pooled findings were 0.75 (95% CI, 0.70-0.81) for HR, 0.86 (95% CI, 0.81-0.92) for ST-HR, and 0.08 (95% CI, 0.06-0.10) for LT-DP. In the secondary analysis, the pooled values for progression-free survival were 0.77 (95% CI, 0.64-0.91) for HR, 1.02 (95% CI, 0.84-1.24) for ST-HR, and 0.10 (95% CI, 0.06-0.14) for LT-DP.Conclusions and RelevanceThis systematic review and meta-analysis of ICI clinical trial results noted consistently larger ST-HRs vs Cox HRs for ICI therapy, with an LT-DP of approximately 10%. These results suggest that Cox HRs may not provide a full picture of survival outcomes when the risk reduction from treatment is not constant, which may aid in the decision-making process of oncologists and patients.

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A meta-analysis on immune checkpoint inhibitor efficacy for advanced non-small cell lung cancer between East Asians versus non-East Asians

Abstract: Background: We conducted a meta-analysis to assess the efficacy of immune checkpoint inhibitors (ICIs)

Cited by 8 publications

References 71 publications

Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features

Inhibitors of PD-1 in Non-Small Cell Lung Cancer: A Meta-Analysis of Clinical and Molecular Features

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis

Analysis of Cancer Survival Associated With Immune Checkpoint Inhibitors After Statistical Adjustment

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