Efficacy and safety of immune checkpoint inhibitors (ICIs) in extensive-stage small cell lung cancer (SCLC)

Ma, Xiaoting; Wang, Shan; Zhang, Yujian; Wei, Huamin; Yu, Jing

doi:10.1007/s00432-020-03362-z

Cited by 13 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Notably, this situation is changing rapidly with the recent approval of the immune checkpoint inhibitors, atezolizumab and durvalumab, to be used in combination with chemotherapy as first-line treatments for ES-SCLC. 6,7 Besides immunotherapies, targeted therapies have also been investigated for treating ES-SCLC. The major molecular mechanisms explored so far include the inhibition of the vascular endothelial growth factor pathway, the inhibition of DNA repair by targeting the poly(adenosine diphosphate-ribose) polymerase (PARP) enzymes, the inhibition of Bcl-2 involved in apoptosis, and the inhibition of the Hedgehog and Notch pathways involved in cell fate regulation.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study

Pan

Shi

et al. 2021

Journal of Thoracic Oncology

View full text Add to dashboard Cite

show abstract

“… 13 , 14 , 15 , 16 , 17 , 18 , 19 Early studies suggest that tRT and ICI are safe and effective in limited-stage SCLC, but this has not yet been found in extensive-stage disease. 13 , 14 , 15 , 18 , 20 , 21 , 22 …”

Section: Introductionmentioning

confidence: 99%

A Real-World Evaluation of Atezolizumab Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC in Canada

Elegbede

Gibson

Fung

et al. 2021

JTO Clinical and Research Reports

View full text Add to dashboard Cite

Introduction The real-world data evaluating treatment outcomes of atezolizumab plus carboplatin-etoposide chemotherapy (atezolizumab) for extensive-stage SCLC (ESCLC) are lacking. Our objective was to evaluate real-world outcomes of ESCLC treated with atezolizumab. Methods A retrospective analysis of provincial patients with ESCLC who started first-line (1L) systemic treatment was conducted. We primarily evaluated the progression-free survival (PFS) and overall survival (OS) outcomes in association with atezolizumab compared with platinum-etoposide chemotherapy (chemotherapy) while adjusting for relevant demographic and clinical factors. Adverse events (AEs) during 1L were evaluated. Results A total of 67 patients were identified. Of the 34 patients who received atezolizumab, 24% had Eastern Cooperative Oncology Group performance status greater than or equal to 2, approximately 50% were more than or equal to 65 years, 21% received cisplatin-etoposide chemotherapy before atezolizumab, and 12% had thoracic radiation (tRT). Within the atezolizumab versus chemotherapy group, the median PFS equals to 6.0 versus 4.3 months ( p = 0.03) whereas OS = 12.8 versus 7.1 months ( p = 0.01). Relative to chemotherapy, the hazard ratio (95% confidence interval) for PFS was 0.53 (0.28–1.02) and OS was 0.42 (0.20–0.88) with atezolizumab. tRT compared with no tRT receipt correlated with reduced death risk (hazard ratio [95% confidence interval] = 0.33 [0.13–0.88]). AE-related treatment withdrawal with atezolizumab was 32% and 15% with chemotherapy ( p = 0.02). Within the tRT subgroup, 25% versus 20% in atezolizumab versus chemotherapy group, respectively, discontinued 1L owing to AE. Conclusions This is the first real-world study revealing comparable survival with that in the IMpower133 trial. Treatment discontinuation from AEs was higher with atezolizumab among Canadian patients with ESCLC. Our data suggest safe use of tRT and chemoimmunotherapy, but its efficacy for ESCLC warrants further study.

show abstract

Efficacy and safety of immune checkpoint inhibitors (ICIs) in extensive-stage small cell lung cancer (SCLC)

Cited by 13 publications

References 36 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

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study

A Real-World Evaluation of Atezolizumab Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC in Canada

Contact Info

Product

Resources

About