Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer: The GOIRC-AIFA FARM6PMFJM Trial

Marcello Tiseo, Luca Boni, Francesca Ambrosio, Andrea Camerini, Editta Baldini, Saverio Cinieri, Matteo Brighenti, Francesca Zanelli, Efisio Defraia, Rita Chiari, Claudio Dazzi, Carmelo Tibaldi, Gianni Michele Turolla, Vito D'Alessandro, Nicoletta Zilembo, Anna Rita Trolese, Francesco Grossi, Ferdinando Riccardi, Andrea Ardizzoni

Research output: Contribution to journalArticle

Abstract

Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.

Original languageEnglish
Pages (from-to)1281-1287
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number12
DOIs
Publication statusPublished - Apr 20 2017

Fingerprint

Small Cell Lung Carcinoma
Etoposide
Cisplatin
Survival
Therapeutics
Disease-Free Survival
Maintenance
Angiogenesis Inhibitors
Bevacizumab
Disease Progression
Survival Rate
Hypertension
Research

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Bevacizumab
  • Cisplatin
  • Disease-Free Survival
  • Etoposide
  • Female
  • Humans
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Small Cell Lung Carcinoma
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

Cite this

Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer : The GOIRC-AIFA FARM6PMFJM Trial. / Tiseo, Marcello; Boni, Luca; Ambrosio, Francesca; Camerini, Andrea; Baldini, Editta; Cinieri, Saverio; Brighenti, Matteo; Zanelli, Francesca; Defraia, Efisio; Chiari, Rita; Dazzi, Claudio; Tibaldi, Carmelo; Turolla, Gianni Michele; D'Alessandro, Vito; Zilembo, Nicoletta; Trolese, Anna Rita; Grossi, Francesco; Riccardi, Ferdinando; Ardizzoni, Andrea.

In: Journal of Clinical Oncology, Vol. 35, No. 12, 20.04.2017, p. 1281-1287.

Research output: Contribution to journalArticle

Tiseo, M, Boni, L, Ambrosio, F, Camerini, A, Baldini, E, Cinieri, S, Brighenti, M, Zanelli, F, Defraia, E, Chiari, R, Dazzi, C, Tibaldi, C, Turolla, GM, D'Alessandro, V, Zilembo, N, Trolese, AR, Grossi, F, Riccardi, F & Ardizzoni, A 2017, 'Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer: The GOIRC-AIFA FARM6PMFJM Trial', Journal of Clinical Oncology, vol. 35, no. 12, pp. 1281-1287. https://doi.org/10.1200/JCO.2016.69.4844
Tiseo, Marcello ; Boni, Luca ; Ambrosio, Francesca ; Camerini, Andrea ; Baldini, Editta ; Cinieri, Saverio ; Brighenti, Matteo ; Zanelli, Francesca ; Defraia, Efisio ; Chiari, Rita ; Dazzi, Claudio ; Tibaldi, Carmelo ; Turolla, Gianni Michele ; D'Alessandro, Vito ; Zilembo, Nicoletta ; Trolese, Anna Rita ; Grossi, Francesco ; Riccardi, Ferdinando ; Ardizzoni, Andrea. / Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer : The GOIRC-AIFA FARM6PMFJM Trial. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 12. pp. 1281-1287.
@article{834009a362414bb5822859bf3e8795ca,
title = "Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer: The GOIRC-AIFA FARM6PMFJM Trial",
abstract = "Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25{\%} and 37{\%} (hazard ratio, 0.78; 95{\%} CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95{\%} CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0{\%} v 6.3{\%} in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.",
keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Cisplatin, Disease-Free Survival, Etoposide, Female, Humans, Lung Neoplasms, Male, Middle Aged, Small Cell Lung Carcinoma, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial",
author = "Marcello Tiseo and Luca Boni and Francesca Ambrosio and Andrea Camerini and Editta Baldini and Saverio Cinieri and Matteo Brighenti and Francesca Zanelli and Efisio Defraia and Rita Chiari and Claudio Dazzi and Carmelo Tibaldi and Turolla, {Gianni Michele} and Vito D'Alessandro and Nicoletta Zilembo and Trolese, {Anna Rita} and Francesco Grossi and Ferdinando Riccardi and Andrea Ardizzoni",
year = "2017",
month = "4",
day = "20",
doi = "10.1200/JCO.2016.69.4844",
language = "English",
volume = "35",
pages = "1281--1287",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "12",

}

TY - JOUR

T1 - Italian, Multicenter, Phase III, Randomized Study of Cisplatin Plus Etoposide With or Without Bevacizumab as First-Line Treatment in Extensive-Disease Small-Cell Lung Cancer

T2 - The GOIRC-AIFA FARM6PMFJM Trial

AU - Tiseo, Marcello

AU - Boni, Luca

AU - Ambrosio, Francesca

AU - Camerini, Andrea

AU - Baldini, Editta

AU - Cinieri, Saverio

AU - Brighenti, Matteo

AU - Zanelli, Francesca

AU - Defraia, Efisio

AU - Chiari, Rita

AU - Dazzi, Claudio

AU - Tibaldi, Carmelo

AU - Turolla, Gianni Michele

AU - D'Alessandro, Vito

AU - Zilembo, Nicoletta

AU - Trolese, Anna Rita

AU - Grossi, Francesco

AU - Riccardi, Ferdinando

AU - Ardizzoni, Andrea

PY - 2017/4/20

Y1 - 2017/4/20

N2 - Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.

AB - Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively ( P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bevacizumab

KW - Cisplatin

KW - Disease-Free Survival

KW - Etoposide

KW - Female

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Small Cell Lung Carcinoma

KW - Clinical Trial, Phase III

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

U2 - 10.1200/JCO.2016.69.4844

DO - 10.1200/JCO.2016.69.4844

M3 - Article

C2 - 28135143

VL - 35

SP - 1281

EP - 1287

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 12

ER -