Dataset Information

Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis.

ABSTRACT:

Background

The efficacy and toxicity profiles for extensive-stage small cell lung cancer (ES-SCLC) are unclear. We aimed to address this gap through a Bayesian network meta-analysis.

Methods

We performed network analysis from randomized controlled trials comparing these treatments: PD-(L)1 inhibitor, CTLA-4 inhibitor, CXCR inhibitor, PARP inhibitor, CDK inhibitor, chemotherapy, and their combinations. Pooled estimations of progression-free survival, overall survival, objective response rate, and toxicity (systematic and specific) were conducted within the Bayesian framework.

Results

Twenty-five trials involving 9 strategies were included. In terms of progression-free survival and overall survival, PD-(L)1 inhibitor combined with cisplatin/carboplatin (P) and etoposide (E) shown the acknowledged superiority than other treatments. The addition of CTLA-4 inhibitor (ipilimumab) to EP had the highest response rate among these regimens, and the combination of chemotherapy (irinotecan) and cisplatin/carboplatin had the greatest probability of performing considerable systematic security. The secondary endpoint was specific adverse events, including vomiting, fatigue, thrombocytopenia, constipation, and decreased appetite; hence we depicted the specific toxicity profile of each regimen. In addition, we identified the differences between PD-1 inhibitors and PD-L1 inhibitors in prolonging overall survival time for the central nervous system (CNS)/liver metastases patients.

Conclusions

EP combined with PD-(L)1 inhibitor followed by CTLA-4 inhibitors or anti-angiogenesis was the considerable treatment with considerable efficacy and safety for ES-SCLC. Each treatment has a unique specific toxicity profile, which needs more attention.

SUBMITTER: Lin G

PROVIDER: S-EPMC10225202 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis.

Lin Guo G Yao Zhuoran Z Kang Kai K Wang Hui H Luo Ren R Lu You Y

Cancer medicine 20230323 9

<h4>Background</h4>The efficacy and toxicity profiles for extensive-stage small cell lung cancer (ES-SCLC) are unclear. We aimed to address this gap through a Bayesian network meta-analysis.<h4>Methods</h4>We performed network analysis from randomized controlled trials comparing these treatments: PD-(L)1 inhibitor, CTLA-4 inhibitor, CXCR inhibitor, PARP inhibitor, CDK inhibitor, chemotherapy, and their combinations. Pooled estimations of progression-free survival, overall survival, objective res ...[more]

PMID: 36951654

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Project description:BackgroundDespite numerous immunotherapy and chemotherapy regimens available for patients with extensive-stage small cell lung cancer (ES-SCLC), it remains unclear which regimen is the most effective and safest; relative studies comparing such regimens are scarce.ObjectiveThe aim of this study was to investigate the efficacy and safety of first-line immunotherapy combinations with chemotherapy for patients with extensive-stage small cell lung cancer. In addition, for the first time, comparisons among the first-line systemic regimens on OS and PFS in ES-SCLC by each time node were made.MethodsDatabases including PubMed, Embase, Cochrane Library, Scopus, Google Scholars, and ClinicalTrials.gov, and major international conferences were searched for randomized controlled trials (RCTs) regarding comparing immunotherapy combinations with chemotherapy as first-line treatments for patients with advanced ES-SCLC from inception to 1 November. Hazard ratios (HRs) and odds ratios (ORs) were generated for dichotomous variants by RStudio 4.2.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events of grade 3 or higher (Grade ≥ 3 AEs).ResultsEventually, a total of nine RCTs reporting 4,352 individuals with nine regimens were enrolled. The regimens were ipilimumabnu (Ipi), atezolizumab (Atez), durvalumab plus tremelimumab (Durv-Trem), durvalumab (Durv), pembrolizumab (Pemb), adebrelimab (Adeb), serplulimab (Serp), atezolizumab plus tiragolumab (Atez-Tira), and nivolumab (Nivo). With regard to OS, serplulimab (HR = 0.63, 95% CI: 0.49 to 0.81) was found to yield the best OS benefit when compared with chemotherapy. Meanwhile, serplulimab had the highest probability (46.11%) for better OS. Furthermore, compared with chemotherapy, serplulimab significantly increased the OS rate from the 6th to the 21st month. With regard to PFS, serplulimab (HR = 0.47, 95% CI: 0.38 to 0.59) was found to yield the best PFS benefit when compared with chemotherapy. Simultaneously, serplulimab had the highest probability (94.48%) for better PFS. Serplulimab was also a long-lasting first-line regimen in both OS and PFS from a longitudinal perspective. In addition, there was no significant difference among the various treatment options for ORR and grade ≥3 AEs.ConclusionConsidering OS, PFS, ORR, and safety profiles, serplulimab with chemotherapy should be recommended as the best therapy for patients with ES-SCLC. Certainly, more head-to-head studies are needed to confirm these findings.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022373291.

Project description:BackgroundOur goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).MethodsThe protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.ResultsA total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.ConclusionPatients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.

Project description:BackgroundCombination regimens of immunotherapy plus chemotherapy have been approved as the first-line and standard of care for extensive-stage small cell lung cancer (ES-SCLC). Novel regimens are continuously being explored, with the ETER701 study being the representative randomized controlled trial (RCT). ETER701 study has assessed the efficacy and safety of chemotherapy with or without anlotinib (multi-target angiogenesis inhibitor) + benmelstobart (programmed cell death ligand 1 inhibitor) (Anl/Ben/CT). There is no evidence-based medicine available proving that Anl/Ben/CT is the optimal regimen due to the lack of direct or indirect comparisons among varying immunotherapy-based regimens. In this study, we aimed to identify the optimal regimen to assist in clinical decision-making.MethodsThe eligible RCTs were identified by searching PubMed, Embase, Cochrane Library databases, and major international conferences. Then, the network meta-analysis was analyzed to compare the efficacy and safety among 15 first-line regimens in ES-SCLC. The Cochrane Risk of Bias Tool was used to assess the risk of bias in included studies.ResultsA total of 12 immunotherapy-related RCTs covering 15 interventions and 6,178 patients with ES-SCLC were included. Overall, most RCTs exhibited a low risk of bias across multiple domains. The results indicated that most immunotherapy-based regimens could significantly prolong progression-free survival (PFS) compared with chemotherapy alone, especially Anl/Ben/CT [hazard ratio (HR) 0.32, 95% confidence interval (CI): 0.25-0.40]. Similar results were observed regarding overall survival (OS), that is, most immunotherapy-related regimens dramatically reduced the risk of death in ES-SCLC, with Anl/Ben/CT being the most prominent (HR 0.61, 95% CI: 0.47-0.80). The Bayesian ranking probabilities showed that Anl/Ben/CT ranked first and serplulimab plus chemotherapy ranked second in both PFS and OS among 15 regimens. Regarding safety, Anl/Ben/CT ranked 3rd, and serplulimab plus chemotherapy ranked 7th.ConclusionsAdding anlotinib and benmelstobart to chemotherapy significantly improved PFS and OS compared with chemotherapy alone or chemotherapy plus immunotherapy, with an acceptable safety profile in patients with ES-SCLC. In conclusion, Anl/Ben/CT could be a new, preferable first-line treatment option but further clinical studies are needed to validate its efficacy and safety.

Project description:IntroductionMany randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients.MethodsMultiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated by CEA.ResultsWe identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively.ConclusionThe NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.

Project description:BackgroundThe prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial.ObjectiveTo evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events.ResultsWe identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.93; risk ratio (RR) 0.90, 95% CI 0.81-1.00) and PFS (HR: 0.81, 95% CI 0.74-0.88; RR 0.96, 95% CI 0.93-0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%).ConclusionIn the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.

Project description:ImportanceCombinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is.ObjectiveTo clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC.Data sourcesElectronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019.Study selectionHead-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included.Data extraction and synthesisData were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model.Main outcomes and measuresMain outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5.ResultsA total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposide-platinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the cumulative ranking curve value, PD-L1 inhibitor plus etoposide-platinum had the highest probability of being ranked first for OS (0.87) and DCR (0.97).Conclusions and relevanceThe findings of this systematic review and network meta-analysis suggest that the combination of a PD-L1 inhibitor (durvalumab and atezolizumab) and etoposide-based chemotherapy may be an optimal first-line treatment option for patients with ES-SCLC patients.

Project description:Introduction: This study evaluated the cost-effectiveness of atezolizumab + chemotherapy vs. chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) in the United States (US). Methods: The three health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the IMpower133 trial. The parametric survival model and mixture cure model were used for the atezolizumab + chemotherapy group to explore the long-term uncertainty of the effect of immunotherapy, and the parametric survival model was used for the chemotherapy group. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from previous studies. Sensitivity analyses were performed to observe model stability. Results: If the mixture cure model was considered for the intervention group, compared with chemotherapy alone, atezolizumab + chemotherapy yielded an additional 0.11 quality-adjusted life-years (QALYs), with an incremental cost of US$84,257. The incremental cost-utility ratio (ICUR) was US$785,848/QALY. If the parametric survival model was considered for the intervention group, atezolizumab + chemotherapy yielded an additional 0.10 QALYs, with an incremental cost of US$84,257; the ICUR was US$827,610/QALY. In the one-way sensitivity analysis, progression-free (PF) and postprogression (PP) utilities were the main drivers. In the scenario analysis (PF utility = 0.673, PP utility = 0.473), the results showed that the ICUR was US$910,557/QALY and US$965,607/QALY when the mixture cure model and parametric survival model was considered for the intervention group, respectively. In the PSA, the probabilities that atezolizumab + chemotherapy would not be cost-effective were 100% if the willingness-to-pay threshold was US$100,000/QALY. Conclusions: The findings of the present analysis suggest that atezolizumab + chemotherapy is not cost-effective in patients receiving first-line treatment for extensive-stage SCLC in the US.

Dataset Information

Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis.

Background

Methods

Results

Conclusions

Publications

Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis.

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