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.

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.

Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (STELLA): Design of a confirmatory, double-blind, randomized, controlled study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20731-e20731 ◽  
Author(s):  
Yaroslav V. Shparyk ◽  
Igor Bondarenko ◽  
Alexandra Paravisini ◽  
Amalia Florez ◽  
Camino Huerga ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung ◽  
Double Blind ◽  
To Receive

e20731 Background: MB02 is a bevacizumab biosimilar developed to stringent guidelines, including non-clinical and preclinical investigations and a clinical trial as first-line treatment in metastatic colorectal cancer (Romera A et al. Lancet Gastroenterol Hepatol 2018;3 (12): 845-855). A clinical trial (STELLA) has been initiated to confirm there are no clinically meaningful differences between MB02 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity (NCT03296163). Methods: STELLA study is a multinational, double-blind, randomized, parallel-group, equivalence study comparing the efficacy and safety of MB02 vs reference bevacizumab plus chemotherapy in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). Subjects aged 18-80 years, with ECOG status ≤1 and histologically confirmed NSCLC not receiving curative intent surgery or systemic therapy for advanced disease are randomized (1:1) to receive: chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) and either MB02 or reference bevacizumab 15 mg/kg every 3 weeks for up to 6 cycles (unless disease progression or treatment intolerance). Randomization is stratified by sex, smoking status, disease diagnosis (newly/recurrent), and stage. After 6 cycles, subjects can continue to receive MB02/reference bevacizumab in monotherapy every 3 weeks (until disease progression, treatment intolerance, death, withdrawal or end of study). The primary objective is to compare the objective response rate (ORR) between arms by week 18 (independently assessed) measured by RECIST v1.1. Progression free survival and overall survival (at 18 and 52 weeks), safety and immunogenicity will be assessed as secondary objectives. A sample size of 600 subjects was assumed providing about 89% power to show equivalence of MB02 plus chemotherapy with reference bevacizumab plus chemotherapy on a primary endpoint of risk ratio based on ORR. To date, 596 subjects have been recruited from more than 15 countries worldwide (Europe, Asia, Latin-America, Africa and Middle-East). At their last meeting in September, 2018 the independent data safety monitoring board (DSMB) recommended that the study continue without change. Clinical trial information: NCT03296163.

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.

Sign in / Sign up

Export Citation Format

Share Document