A systematic review of survival following anti-cancer treatment for small cell lung cancer

Jones, G.; Elimian, Kelly Osezele; Baldwin, David R; Hubbard, Richard; McKeever, Tricia M.

doi:10.1016/j.lungcan.2019.12.015

Cited by 33 publications

(21 citation statements)

References 163 publications

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“…Since SCLC has a very short survival time, new treatment strategies are urgently needed. The clinical efficacy of immunotherapies has been observed in patients with refractory or metastatic SCLC [12,[19][20][21][22][23]. The phase II KEYNOTE-158 study [21] showed that the PFS of pembrolizumab for relapsed SCLC was 2.0 months, the median OS was 9.1 months, and the one-year PFS and OS were 16.8% and 40.2%, respectively.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Chen

Chang

et al. 2020

Cancers

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Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits compared with EP alone in terms of OS (Hazard Ratio HR = 0.67, 95% Confidence Interval CI = 0.46–0.98 for nivolumab, HR = 0.70, 95% CI = 0.54–0.91 for atezolizumab, HR = 0.73, 95% CI = 0.59–0.90 for durvalumab) but no significant differences were observed for pembrolizumab or ipilimumab. The probability of nivolumab being ranked first among all treatment arms was highest (SCURA = 78.7%, Prbest = 46.7%). All EP plus ICI combinations had a longer PFS compared with EP alone (HR = 0.65, 95% CI = 0.46–0.92 for nivolumab, HR = 0.77, 95% CI = 0.61–0.96 for atezolizumab, HR = 0.78, 95% CI = 0.65–0.94 for durvalumab, HR = 0.75, 95% CI = 0.61–0.92 for pembrolizumab), and nivolumab was ranked first in terms of PFS (SCURA = 85.0%, Prbest = 66.8%). In addition, nivolumab had the highest probability of grade 3–4 adverse events (SUCRA = 84.8%) in our study. We found that nivolumab had the best PFS and OS in all combinations of ICIs and EP, but nivolumab also had the highest probability of grade 3–4 adverse events in our network meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.

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Section: Discussionmentioning

confidence: 99%

Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Chen

Chang

et al. 2020

Cancers

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“…In comparison a systematic review that examined oneyear survival from mostly clinical trial research estimated 1 year survival to be approximately 73% in LD-SCLC and 38% in ED-SCLC (14). Better survival in clinical trials can be explained by selection bias.…”

Section: One-year Survivalmentioning

confidence: 99%

Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data

Jones¹,

Khakwani²,

Pascoe³

et al. 2021

Ann Palliat Med

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Background: The mainstay of treatment for small cell lung cancer (SCLC) involves platinum doublet chemotherapy but the optimal duration, 4 vs. 6 cycles, is not known. Concurrent thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is recommended for fit individuals with limited stage. However, outside of clinical trials, the efficacy of sequential thoracic radiotherapy and PCI for extensive stage is uncertain.Methods: This retrospective, observational, cohort study used English national lung cancer data to determine the factors associated with survival for all people diagnosed with SCLC. More precisely, for individuals who received chemotherapy, we examined survival by the chemotherapy duration, thoracic radiotherapy dose and the use of PCI.Results: In total 6,438 people were diagnosed with SCLC. We identified that male sex (OR 0.7; 95% CI: 0.62-0.80), increasing age (P=0.01) greater comorbidity (P≤0.01), extensive stage (OR 0.21; 95% CI: 0.19-0.25) and worse performance status (PS2 vs. PS0 adjusted OR 0.38 95% CI: 0.31-0.48) were associated with reduced 1-year survival. Receipt of chemotherapy augmented survival. We analysed data for 1,761 people who had received chemotherapy. Thoracic radiotherapy (≥30 Gy for extensive stage and ≥40 Gy for limited stage) and PCI were independently associated with better survival (P≤0.01 for each), but 6 cycles of chemotherapy instead of 4 was not (limited stage adjusted OR 0.97; 95% CI: 0.48-1.97) extensive stage adjusted OR 1.34; 95% CI: 0.81-2.21). Conclusions:Extending chemotherapy beyond 4 cycles to 6 does not augment survival. Appropriately prescribed thoracic radiotherapy and PCI can prolong survival in both limited and extensive stage SCLC.

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“…Although the majority of ES-SCLC occur mutation of TP53(90%) and RB1(65%), the target driven gene is not clear, which leads to limited progress in the treatment of ES-SCLC [4]. In the pre-immunotherapy era, platinum based(carboplatin or cisplatin) etoposide chemotherapy has always been the standard-of-care first-line treatment for ES-SCLC [5][6][7], which is associated with poor outcomes (a 5-year survival rate of 6%-7% and median over survival(OS) of approximately10 months) [8][9]. More efficacious first-line therapy is urgently needed to improve this prognosis.…”

Section: Introductionmentioning

confidence: 99%

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer in the United States

Liu¹,

Luo²,

Peng³

et al. 2021

Preprint

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Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

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A systematic review of survival following anti-cancer treatment for small cell lung cancer

Abstract: This is a comprehensive analysis of early and late survival following treatments recommended by the European Society of Medical Oncology for small cell lung cancer. Our survival benchmarks can inform the treatment selection process going forward.

Cited by 33 publications

References 163 publications

Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer in the United States

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