Abstract
BackgroundThis meta-analysis aimed to investigate the efficacy of immune checkpoint inhibitor (ICI)-based therapy in non-small cell lung cancer (NSCLC) patients with different clinical and molecular characteristics such as age, sex, histological type, performance status (PS), smoking status, driver mutations, metastatic site, region and number of prior systemic regimens.MethodsA systematic literature search was conducted in PubMed, Embase, and the Cochrane library databases to identify qualified randomized controlled trials (RCTs). The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS).ResultsA total of 19 RCTs were included in this meta-analysis. ICI-based therapy significantly improved OS compared with non-ICI therapy in patients aged <65 years (HR, 0.74; P<0.00001), 65-74 years (HR, 0.73; P<0.00001), receiving first-line (HR, 0.75; P<0.00001) or second-line (HR, 0.72; P<0.00001) treatment, current or previous smokers (HR, 0.76; P<0.00001), and EGFR wild-type patients (HR, 0.76; P<0.00001), but not in patients aged ≥75 years (HR, 0.91; P=0.50), receiving third-line treatment (HR, 0.93; P=0.55), never smokers (HR, 0.84; P=0.10), or EGFR mutant patients (HR, 0.99; P=0.92). No statistical OS improvement was observed in KRAS mutant (HR, 0.68; P=0.05) or KRAS wild-type (HR, 0.95; P=0.65) patients. Immunotherapy improved OS in NSCLC patients, regardless of sex (male or female), histological type (squamous or non-squamous NSCLC), PS (0 or 1), metastatic site (brain or liver metastases), and region (East Asia or America/Europe) (all P<0.05). Subgroup analysis showed that the survival benefit of ICIs in patients with brain metastases was observed in first-line combination therapy (P<0.05), but not in second or more line monotherapy (P>0.05). Programmed death-1 (PD-1) inhibitors significantly prolonged OS in patients with liver metastases compared with non-ICI therapy (P=0.0007), but PD-L1 inhibitors did not (P=0.35). Similar results were observed in the combined analysis of PFS.ConclusionsAge, smoking status, EGFR mutation status, and number of prior systemic regimens predicted the efficacy of immunotherapy. While sex, histological type, PS 0 or 1, KRAS mutation status and region were not associated with the efficacy of ICIs. Patients with liver metastases benefited from anti-PD-1-based therapy, and those with brain metastases benefited from first-line ICI-based combination therapy.Systematic Review Registrationhttp://www.crd.york.ac.uk/prospero, identifier CRD42020206062.
Highlights
Immunotherapy is a key and effective method for the treatment of cancer patients, which improves the treatment mode of cancer
The inclusion criteria designed according to PICOS structure were as follows: (I) Population: non-small cell lung cancer (NSCLC) patients. (II) Intervention: immune checkpoint inhibitor (ICI) group. (III) Control: non-ICI group. (IV) Outcomes: overall survival (OS) or progression-free survival (PFS) of prespecified subgroups by age, sex, region, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score, smoking status, brain metastases, liver metastases, driver mutations, histological type and number of prior systemic regimens. (V) Study: randomized controlled trials (RCTs). (VI) All studies were available in full text
IMpower150 study included two experimental groups: carboplatin plus paclitaxel plus atezolizumab, and carboplatin plus paclitaxel plus bevacizumab plus atezolizumab, all of which were compared with the control group: carboplatin plus paclitaxel plus bevacizumab [18, 19]
Summary
Immunotherapy is a key and effective method for the treatment of cancer patients, which improves the treatment mode of cancer. A number of large-scale randomized controlled trials (RCTs) have demonstrated that ICIs represented by programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, whether used as monotherapy or as combination therapy, provide long-term survival and lasting benefits for patients with non-small cell lung cancer (NSCLC) [2,3,4,5,6]. Our previous meta-analysis has demonstrated that PD-L1 expression detected by immunohistochemical is an effective biomarker for predicting the efficacy of checkpoint inhibitors in NSCLC. This meta-analysis aimed to investigate the efficacy of immune checkpoint inhibitor (ICI)-based therapy in non-small cell lung cancer (NSCLC) patients with different clinical and molecular characteristics such as age, sex, histological type, performance status (PS), smoking status, driver mutations, metastatic site, region and number of prior systemic regimens
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