Darbepoetin-?? does not affect overall survival in patients with extensive-stage small-cell lung cancer

2007 ◽  
Vol &NA; (1149) ◽  
pp. 5
Author(s):  
&NA;
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Extensive Stage

scholarly journals Initial management of small-cell lung cancer (limited- and extensive-stage) and the role of thoracic radiotherapy and first-line chemotherapy: a systematic review

2019 ◽  
Vol 26 (3) ◽  
Author(s):  
A. Sun ◽  
L. D. Durocher-Allen ◽  
P. M. Ellis ◽  
Y. C. Ung ◽  
J. R. Goffin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Agent ◽  
Extensive Stage

Background Patients with limited-stage (ls) or extensive-stage (es) small-cell lung cancer (sclc) are commonly given platinum-based chemotherapy as first-line treatment. Standard chemotherapy for patients with ls sclc includes a platinum agent such as cisplatin combined with the non-platinum agent etoposide. The objective of the present systematic review was to investigate the efficacy of adding radiotherapy to chemotherapy in patients with es sclc and to determine the appropriate timing, dose, and schedule of chemotherapy or radiation for patients with sclc.Methods The medline and embase databases were searched for randomized controlled trials (rcts) comparing treatment with radiotherapy plus chemotherapy against treatment with chemotherapy alone in patients with es sclc. Identified rcts were also included if they compared various timings, doses, and schedules of treatment for patients with es sclc or ls sclc.Results Sixty-four rcts were included. In patients with ls sclc, overall survival was greatest with platinum– etoposide compared with other chemotherapy regimens. In patients with es sclc, overall survival was greatest with chemotherapy containing platinum–irinotecan than with chemotherapy containing platinum–etoposide (hazard ratio: 0.84; 95% confidence interval: 0.74 to 0.95; p = 0.006). The addition of radiation to chemotherapy for patients with es sclc showed mixed results. There was no conclusive evidence that the timing, dose, or schedule of thoracic radiation affected treatment outcomes in sclc.Conclusions In patients with ls sclc, cisplatin–etoposide plus radiotherapy should remain the standard therapy. In patients with es sclc, the evidence is insufficient to recommend the addition of radiotherapy to chemotherapy as standard practice to improve overall survival. However, on a case-by-case basis, radiotherapy might be added to reduce local recurrence. The most commonly used chemotherapy is platinum–etoposide; however, platinum– irinotecan can be considered.

scholarly journals Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133)

2021 ◽  
Vol 39 (6) ◽  
pp. 619-630
Author(s):  
Stephen V. Liu ◽  
Martin Reck ◽  
Aaron S. Mansfield ◽  
Tony Mok ◽  
Arnaud Scherpereel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Double Blind ◽  
Treatment Benefit ◽  
Extensive Stage

PURPOSE: IMpower133 (ClinicalTrials.gov identifier: NCT02763579 ), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported. PATIENTS AND METHODS: Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collected; PD-L1 testing was not required for enrollment. The two primary end points, investigator-assessed PFS and OS, were statistically significant at the interim analysis. Updated OS and PFS and exploratory biomarker analyses were conducted. RESULTS: Patients received atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). At the updated analysis, median follow-up for OS was 22.9 months; 302 deaths had occurred. Median OS was 12.3 and 10.3 months with atezolizumab plus CP/ET and placebo plus CP/ET, respectively (hazard ratio, 0.76; 95% CI, 0.60 to 0.95; descriptive P = .0154). At 18 months, 34.0% and 21.0% of patients were alive in atezolizumab plus CP/ET and placebo plus CP/ET arms, respectively. Patients derived benefit from the addition of atezolizumab, regardless of PD-L1 immunohistochemistry or bTMB status. CONCLUSION: Adding atezolizumab to CP/ET as 1L treatment for ES-SCLC continued to demonstrate improved OS and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.

Randomized Study of CODE Versus Alternating CAV/EP for Extensive-Stage Small-Cell Lung Cancer: An Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group

1999 ◽  
Vol 17 (8) ◽  
pp. 2300-2300 ◽  
Author(s):  
Nevin Murray ◽  
Robert B. Livingston ◽  
Frances A. Shepherd ◽  
Keith James ◽  
Benny Zee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Chemotherapy Regimen ◽  
Small Cell ◽  
Small Cell Lung ◽  
Weekly Chemotherapy ◽  
Thoracic Irradiation ◽  
Extensive Stage

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P = .006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0.91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Immunotherapy versus standard chemotherapy for treatment of extensive-stage small-cell lung cancer: a systematic review

Immunotherapy ◽  
2021 ◽  
Author(s):  
Xingyu Liu ◽  
Huifang Xing ◽  
Hongbing Zhang ◽  
Hongyu Liu ◽  
Jun Chen
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Extensive Stage

Aim: We conducted a systematic review and network meta-analysis to evaluate the efficacy of immunotherapy versus chemotherapy to treat extensive-stage small-cell lung cancer. Methods: We analyzed several eligible clinical trials using fixed or random-effects models to evaluate relative treatment effects depending on heterogeneity. Results: In the experimental group, immunotherapy showed significant improvement in overall survival (hazard ratio [HR]: 0.82; 95% CI: 0.74–0.89; I2 = 31.4%; p < 0.001) and progression-free survival (HR: 0.77; 95% CI: 0.80–0.83; I2 = 22.7%; p < 0.001). Conclusion: Immunotherapy is likely to significantly improve extensive-stage small-cell lung cancer patients' overall survival and progression-free survival compared with standard chemotherapy. Anti-PD L1 exhibited superior overall survival compared with anti-PD 1 and anti-CTLA4.

Role of radiation in extensive stage small cell lung cancer: a National Cancer Database registry analysis

2021 ◽  
Author(s):  
Saad Sheikh ◽  
Asoke Dey ◽  
Sujay Datta ◽  
Tarun K Podder ◽  
Charulata Jindal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Propensity Score ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
National Cancer Database ◽  
Small Cell Lung ◽  
Extensive Stage

The role of prophylactic cranial irradiation (PCI) and thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer remains controversial. The authors examined the National Cancer Database and identified patients with extensive-stage small cell lung cancer with no brain metastasis. Patients were excluded if they died 30 days from diagnosis, did not receive polychemotherapy, had other palliative radiation or had missing information. A propensity score-matched analysis was also performed. A total of 21,019 patients were identified. The majority of patients did not receive radiation (69%), whereas 10% received PCI and 21% received TRT. The addition of PCI and TRT improved median survival and survival at 1 and 2 years (p ≤ 0.05). The propensity score-matched analysis confirmed the same overall survival benefit with both PCI and TRT. This registry-based analysis of >1500 accredited cancer programs shows that PCI and TRT are not commonly utilized for extensive-stage small cell lung cancer patients who are treated with multiagent chemotherapy. The addition of PCI and TRT significantly improves overall survival in this otherwise poor prognostic group. Further research is needed to confirm the role of PCI and TRT, especially in the era of improved systemic therapy.

scholarly journals Consideration of Surrogate Endpoints for Overall Survival Associated With First-Line Immunotherapy in Extensive-Stage Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Zhang ◽  
Shuang Li ◽  
Yanan Cui ◽  
Peiyan Zhao ◽  
Xiaodan Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Effect ◽  
Small Cell ◽  
Surrogate Endpoints ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and chemotherapy is known to improve overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). ICIs have different response patterns and survival kinetics characteristics from those of the traditional chemotherapy. In first-line treatment for ES-SCLC, there is an urgent need for surrogate endpoints for the early and accurate prediction of OS. This study aimed to assess progression-free survival (PFS), milestone OS rate, milestone restricted mean survival time (RMST), overall response rate (ORR), and disease control rate (DCR) as proposed surrogate endpoints for OS in ES-SCLC for first-line immunotherapy trials.MethodsBetween January 1, 2013, and December 2020, published articles on randomized clinical trials of ICIs plus chemotherapy in patients with ES-SCLC as first-line therapy were searched in PubMed. Abstracts from the ESMO, ASCO, and WCLC, reported from 2018 onwards, were also searched. A weighted regression analysis based on the weighted least squares method was performed on log-transformed estimates of treatment effect, and the determination coefficient (R2) was calculated to evaluate the association between treatment effect on the surrogate endpoint and OS.ResultsSeven trials, representing 3,009 patients, were included to make up a total of 16 analyzed arms. The ratio of the 12-month OS milestone rate (r = −0.790, P = 0.011, R2 = 0.717) and 12-month OS milestone RMST (r = 0.798, P = 0.010, R2 = 0.702) was strongly correlated with the hazard ratio (HR) for OS. The strongest association was observed between the ratio of the 24-month OS milestone RMST and the HR for OS (r = 0.922, P = 0.001, R2 = 0.825). No associations were observed between the HR for OS and PFS and the RR for ORR and DCR.ConclusionsThe results suggested a strong correlation among the ratio of OS milestone rates at 12 months, ratios of OS milestone RMSTs at 12 and 24 months, and HR for OS. The results indicate that OS milestone rates and OS milestone RMSTs could be considered surrogate endpoints of OS in future first-line immunotherapy trials for ES-SCLC.

scholarly journals Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Abdulhakim A. A. Abunasser ◽  
Jinmin Xue ◽  
Ehab J. A. Balawi ◽  
Yuxi Zhu
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Extensive Stage

The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the same traditional regimen with etoposide and platinum (EP) as the mainstay of treatment with poor prognosis. This meta-analysis aims to assess the effect of adding Immune Checkpoint Inhibitors (CPIs) such as (ipilimumab, atezolizumab, pembrolizumab, and durvalumab) to the traditional EP regimen for small-cell lung cancer extensive stage (ES-SCLC). We searched through PubMed looking for studies that compare between EP and CPIs, with EP alone, and only Phase III randomized controlled trials were considered eligible for this study. A total of 3645 papers were the results of the initial search, and only 4 studies met our criteria. Each investigator extracted the data independently using the PRISMA MODEL (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Each author used a prespecified sheet. The primary endpoint was to calculate OS (overall survival) and PFS (progression-free survival) hazard ratios for both arms. We found that adding EP plus CPIs increased both OS (HR, 95% CI 0.80 [0.70, 0.93], P  = 0.0001, I2 = 49%) and PFS (HR95% CI 0.81 [0.74, 0.88], P  < 0.00001, I2 = 0%). On the other hand, ORR (overall response rate) was not affected by the addition of CPIs to EP compared to EP alone, and the same was true for adverse events. To conclude, CTLA-4 alone is not encouraging, but PD-1/PD-L1 adds survival benefits. A combined treatment regimen shows to be more effective, improving overall survival rate Durvalumab and atezolizumab showed improvement for OS, but pembrolizumab and ipilimumab did not show a significant increase of OS over EP; however, pembrolizumab showed significant prolongation of the disease-free period.

Phase III Study of Pemetrexed Plus Carboplatin Compared With Etoposide Plus Carboplatin in Chemotherapy-Naive Patients With Extensive-Stage Small-Cell Lung Cancer

2009 ◽  
Vol 27 (28) ◽  
pp. 4787-4792 ◽  
Author(s):  
Mark A. Socinski ◽  
Egbert F. Smit ◽  
Paul Lorigan ◽  
Kartik Konduri ◽  
Martin Reck ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Study ◽  
Extensive Stage ◽  
Grade 3

Purpose Following a phase II trial in which pemetrexed-platinum demonstrated similar activity to that of historical etoposide-platinum controls, a phase III study was conducted to compare pemetrexed-carboplatin with etoposide-carboplatin for the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Patients and Methods Chemotherapy-naive patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status of zero to 2 were randomly assigned to receive pemetrexed-carboplatin (pemetrexed 500 mg/m2 on day 1; carboplatin at area under the serum concentration-time curve [AUC] 5 on day 1) or etoposide-carboplatin (etoposide 100 mg/m2 on days 1 through 3; carboplatin AUC 5 on day 1) every 3 weeks for up to six cycles. The primary objective of the study was noninferiority of pemetrexed-carboplatin overall survival with a 15% margin. Results Accrual was terminated with 908 of 1,820 patients enrolled after results of a planned interim analysis. In the final analysis, pemetrexed-carboplatin was inferior to etoposide-carboplatin for overall survival (median, 8.1 v 10.6 months; hazard ratio [HR],1.56; 95% CI, 1.27 to 1.92; log-rank P < .01) and progression-free survival (median, 3.8 v 5.4 months; HR, 1.85; 95% CI, 1.58 to 2.17; log-rank P < .01). Objective response rates were also significantly lower for pemetrexed-carboplatin (31% v 52%; P < .001). Pemetrexed-carboplatin had lower grade 3 to 4 neutropenia, febrile neutropenia, and leukopenia than etoposide-carboplatin; grade 3 to 4 thrombocytopenia was comparable between arms and anemia was higher in the pemetrexed-carboplatin arm. Conclusion Pemetrexed-carboplatin is inferior for the treatment of ES-SCLC. Planned translational research and pharmacogenomic analyses of tumor and blood samples may help explain the study results and provide insight into new treatment strategies.

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