Strengths and Weaknesses of Immunotherapy for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of 12 Randomized Controlled Trials

Abstract

BackgroundLung 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 FindingsWe 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.ConclusionsImmunotherapy 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.

Treatment-related Lymphopenia in Patients With Stage III Non-Small-Cell Lung Cancer

“…In addition, pathologic studies have found that patients with intense lymphocytic infiltration of their solid tumors have longer survivals rates than those who do not (3–6). These and other related observations led to extensive efforts to develop vaccines and other immunologic approaches in an attempt to enhance the immune system’s effect against invasive cancers (7–9). …”

Antitumor Activity of Lentivirus-mediated Interleukin -12 Gene Modified Dendritic Cells in Human Lung Cancer in Vitro

“…The aim of immunotherapy is to eliminate cancer cells through the activation of host immunity by using biological response modifying polysaccharides, monoclonal antibody and cytokines. (Wang et al, 2012). Interleukin-12 is aheterodimeric cytokine composed of two subunits (p35 and p40) both of which are required for the secretion of the active form of IL-12p70, primarily produced by APCs and exert pleiotropic effects on immune effector cells (Tamandani et al, 2009).…”

“…Gene therapy provides a new clinic strategy to enhance the immune function of tumor immunity. After activation by stimulated DCs, auxiliary T lymphocytes and CTLs are capable of killing tumors, which is the theoretical basis of tumor vaccines (Wang et al, 2012). DCs based anti tumor immunotherapy have strong ability to stimulate naïve T lymphocytes and induce effective anti-tumor responses (Guermonprez et al, 2002).…”

Polymer-Based DNA Delivery Systems for Cancer Immunotherapy

“…The stereochemistry of such carbohydrate ligands is diffi cult to control, and the products are diffi cult to purify. A frequently used alternative for carbohydrate ligands are antibodies raised against DC receptors (i.e., integrin CD11c/CD18 [ 55 ], Fc receptors [ 67 ], DEC-205 [ 7 ], DC-SIGN [ 68 ] and MR [ 69 ]), but these, even when humanized, may still elicit adverse immune responses that decrease the effi ciency of treatment and induce auto-immune side-effects [ 70 ].…”