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Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Background: This meta-analysis aimed to explore if immunotherapy or chemotherapy alone or in combination is a better first line treatment strategy for advanced non-small cell lung cancer (NSCLC) patients. Methods: Electronic databases including Google Scholar, PMC, PubMed, EMBASE, Scopus and the major conference proceedings were searched for relevant randomized controlled trials (RCTs) comparing outcomes of immune-checkpoint inhibitor combined with chemotherapy or immune-checkpoint inhibitor alone over chemotherapy alone in patients with advanced NSCLC without previous treatment. Study heterogeneity was assessed using the I2 test. Results: A total of 14 RCTs including 8,081 treatment naïve advanced NSCLC patients were enrolled in this study. Our results showed that in comparison to chemotherapy alone, introducing immunotherapy into first-line chemotherapy has significant benefit in tumor response (RR, 1.27; 95% CI, 1.09 to 1.48), progression-free survival (PFS) (HR, -0.43; 95% CI, -0.56 to -0.31), and overall survival (OS) (HR, -0.30; 95% CI, -0.45 to -0.14) but with an increased risk of grade3 - 5 toxicity (RR, 1.11; 95% CI, 1.04 to 1.18). The pooled results of comparison of immune therapy alone with chemotherapy alone in selected patients with positive expression of Programmed Death-ligament (PD-L1) or with a high tumor mutational burden, demonstrated similar tumor response (RR, 1.13; 95% CI, 0.88 to 1.46), 3 - 5 grade toxicity (RR, 0.69; 95% CI, 0.40 to 1.19) and long-term outcomes, including OS (HR, -0.20; 95% CI, -0.43 to 0.03) and PFS (HR, -0.24; 95% CI, -0.61 to 0.14). Conclusions: Our meta-analysis showed the superiority of combination therapy over monotherapy with chemotherapeutic agents in terms of tumor response, and long-term survival, but with an increased the 3 - 5 grade toxicity. And immune-checkpoint inhibitors alone showed similar tumor response, toxicity and long-term outcomes compared to platinum-based chemotherapy in selected patients.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6856743 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Chen Yuqiao Y Zhou Yuan Y Tang Lu L Peng Xiong X Jiang Hong H Wang Guo G Zhuang Wei W

Journal of Cancer 20191017 25

<b>Background</b>: This meta-analysis aimed to explore if immunotherapy or chemotherapy alone or in combination is a better first line treatment strategy for advanced non-small cell lung cancer (NSCLC) patients. <b>Methods</b>: Electronic databases including Google Scholar, PMC, PubMed, EMBASE, Scopus and the major conference proceedings were searched for relevant randomized controlled trials (RCTs) comparing outcomes of immune-checkpoint inhibitor combined with chemotherapy or immune-checkpoint ...[more]

PMID: 31772659

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.MethodsOur study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.ResultsCompared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.ConclusionOur study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registrationhttps://www.clinicaltrials.gov/ , OMESIA, NCT05129202.

Project description:BackgroundResponse to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.MethodsThe data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People's Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.ResultsForty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs . 15.5 months, P = 0.0005) and OS (11.1 months vs . not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs . 15.5 months, P = 0.0532) rather than OS ( P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs . 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS ( P = 0.0052) but not OS ( P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[ϕ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4).ConclusionsMetastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

Project description:Background: Although smoking status has potential as a biomarker for immune checkpoint blockade in advanced non-small cell lung cancer (NSCLC), its clinical significance remains obscure. This meta-analysis aims to assess the impact of the smoking status on the efficacy of first-line immunotherapy and to find better treatment in never-smoker and ever-smoker patients. Methods: We searched the MEDLINE, EMBASE, and Cochrane database for trials comparing immunotherapy with conventional chemotherapy as front-line treatment for advanced NSCLC. Random-effects models were used to pool estimates of hazard ratios (HRs) for overall survival with 95% confidence intervals (CIs). Predefined subgroup analysis was performed to investigate the difference in the efficacy between the single checkpoint blockade and checkpoint inhibitor plus chemotherapy combination in the never-smokers and current/former smokers. Results: Twelve trials involving 6,446 patients were included in the analysis. A statistically significant overall survival benefit over conventional chemotherapy was found for both checkpoint inhibitor monotherapy (HR, 0.71; 95% CI, 0.59-0.85) and checkpoint inhibitor plus chemotherapy (HR, 0.75; 95% CI, 0.63-0.90) in the current/former smoker group. There was no subgroup difference between monotherapy and combination treatment (p=0.67). However, there was an inconsistent survival outcome in the never-smoker group; checkpoint blockade monotherapy did not show significantly better efficacy than chemotherapy alone (HR, 1.05; 95% CI, 0.81-1.37), but combination treatment showed an overall survival benefit (HR, 0.64; 95% CI, 0.43-0.94). A significant subgroup difference existed between monotherapy and combination therapy (p=0.04). Similarly, there was a significant difference in efficacy of monotherapy between the current/former smoker and never-smoker group (p=0.01), but the efficacy of the combination treatment was comparable between the two groups (p=0.45). Conclusion: Smoking status, which is easily available information, could be used as a guide in clinical practice to choose better treatment in the front-line setting for advanced NSCLC patients.

Project description:Objective: This network meta-analysis will provide a complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC). Methods: We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and ClinicalTrials.gov. Risk ratios (RRs) and 95% confidence interval (CI) were used to compare the rate of immune-related adverse events (irAEs) for different ICIs-based treatments using pairwise and network meta-analysis with random effects. Results: For dermatologic irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (97.4%), pembrolizumab (80.1%), nivolumab (67.1%), pembrolizumab + platinum (43.3%), atezolizumab + platinum (39.9%), durvalumab (17.5%), platinum-based chemotherapy (4.7%). For colitis, the corresponding ranking of incidences of the six groups from high to low was: atezolizumab + platinum (77.1%), nivolumab (67.3%), pembrolizumab (60.5%), durvalumab (45.2%), pembrolizumab + platinum (41.4%), platinum-based chemotherapy (8.5%). For endocrine irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (79.1%), durvalumab (69.1%), pembrolizumab (61.9%), atezolizumab + platinum (60.4%),nivolumab (45.7%), pembrolizumab + platinum (33.5%), platinum-based chemotherapy (0.3%). For pneumonitis, the corresponding ranking of incidences of the seven groups from high to low was: pembrolizumab (99.3%), pembrolizumab + platinum (65.1%), durvalumab (62.2%), atezolizumab + platinum (56%), nivolumab (35.9%), platinum-based chemotherapy (18.1%),atezolizumab (13.3%). For hepatitis, the corresponding ranking of incidences of the six groups from high to low was: pembrolizumab (71.2%), pembrolizumab + platinum (64.3%), durvalumab (56.4%), atezolizumab + platinum (53.8%), nivolumab (44.5%), platinum-based chemotherapy (9.8%). Conlusion: In addition to platinum-based chemotherapy, durvalumab for dermatologic and liver irAEs, pembrolizumab for gastrointestinal irAEs, pembrolizumab + platinum for endocrine irAEs, and atezolizumab for pneumonitis may be associated with lower rates of irAEs than other immune-based regimens. Nivolumab + ipilimumab for dermatologic and endocrine irAEs, atezolizumab + platinum for colitis, and pembrolizumab for pneumonitis and hepatitis may be associated with higher rates of irAEs.

Project description:Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non-small cell lung carcinoma (NSCLC). To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy vs. chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis. Data Sources: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4,646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab, and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%), and 363 (8%) of patients, respectively. The patients were randomized to receive first-line chemotherapy plus a checkpoint inhibitor vs. first-line chemotherapy, 2,978 patients for the OS endpoint and first-line chemotherapy plus a checkpoint inhibitor vs. first-line chemotherapy, 1,740 patients in the PFS endpoint. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Notably within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P < 0.00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P < 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) and across PDL1 subgroups. Conclusion and Relevance: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials. The findings of this meta-analysis could assist in the design and interpretation of future trials and in economic analyses.

Dataset Information

Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Publications

Immune-Checkpoint Inhibitors as the First Line Treatment of Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.

Similar Datasets

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