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Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials.

Wang J, Zou ZH, Xia HL, He JX, Zhong NS, Tao AL - PLoS ONE (2012)

Bottom Line: Lung cancer is one of the leading causes of cancer death worldwide.Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant.Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Municipal Key Laboratory of Allergy and Clinical Immunology, Allergy Research Branch of the State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

ABSTRACT

Background: Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs.

Methodology and principal findings: We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.

Conclusions: Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.

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Related in: MedlinePlus

Forest plot of comparison of partial response of 8 included studies (Stage IIIA, IIIB, or IV NSCLC).P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of data markers are proportional to the number of PR rate events in the trials. CI, confidence interval; HR, hazard ratio.
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pone-0032695-g005: Forest plot of comparison of partial response of 8 included studies (Stage IIIA, IIIB, or IV NSCLC).P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of data markers are proportional to the number of PR rate events in the trials. CI, confidence interval; HR, hazard ratio.

Mentions: Because of no heterogeneity, fixed-effect models were used to analyze total effective rates and PR rates of total unstratified immunotherapy group and all subgroups (Figures 4 and 5). The overall analysis demonstrated that immunotherapy substantially improved both the total effective rate (HR = 1.19, 95% CI = 1.06–1.34; Z = 3.01, P = 0.003) and PR rate (HR = 1.23, 95% CI = 1.08–1.40, Z = 3.07, P = 0.002) compared with the control arms. mAb therapy significantly improved the total effective rate (HR = 1.27, 95% CI = 1.11–1.46, Z = 3.42, P = 0.0006) and PR rate (HR = 1.27, 95% CI = 1.10–1.46, Z = 3.32, P = 0.001), whereas cytokine and vaccine immunotherapy both generated no statistically significant improvement.


Strengths and weaknesses of immunotherapy for advanced non-small-cell lung cancer: a meta-analysis of 12 randomized controlled trials.

Wang J, Zou ZH, Xia HL, He JX, Zhong NS, Tao AL - PLoS ONE (2012)

Forest plot of comparison of partial response of 8 included studies (Stage IIIA, IIIB, or IV NSCLC).P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of data markers are proportional to the number of PR rate events in the trials. CI, confidence interval; HR, hazard ratio.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293858&req=5

pone-0032695-g005: Forest plot of comparison of partial response of 8 included studies (Stage IIIA, IIIB, or IV NSCLC).P values are from P-for-effect modification testing for heterogeneity within or across the groups of regimens. The sizes of data markers are proportional to the number of PR rate events in the trials. CI, confidence interval; HR, hazard ratio.
Mentions: Because of no heterogeneity, fixed-effect models were used to analyze total effective rates and PR rates of total unstratified immunotherapy group and all subgroups (Figures 4 and 5). The overall analysis demonstrated that immunotherapy substantially improved both the total effective rate (HR = 1.19, 95% CI = 1.06–1.34; Z = 3.01, P = 0.003) and PR rate (HR = 1.23, 95% CI = 1.08–1.40, Z = 3.07, P = 0.002) compared with the control arms. mAb therapy significantly improved the total effective rate (HR = 1.27, 95% CI = 1.11–1.46, Z = 3.42, P = 0.0006) and PR rate (HR = 1.27, 95% CI = 1.10–1.46, Z = 3.32, P = 0.001), whereas cytokine and vaccine immunotherapy both generated no statistically significant improvement.

Bottom Line: Lung cancer is one of the leading causes of cancer death worldwide.Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant.Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.

View Article: PubMed Central - PubMed

Affiliation: Guangzhou Municipal Key Laboratory of Allergy and Clinical Immunology, Allergy Research Branch of the State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

ABSTRACT

Background: Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs.

Methodology and principal findings: We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events.

Conclusions: Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.

Show MeSH
Related in: MedlinePlus