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.

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. - ISSN 0732-183X. - 35:12(2017), pp. 1281-1287. [10.1200/JCO.2016.69.4844]

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;BRIGHENTI, Matteo;Dazzi, Claudio;
2017-01-01

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.
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 / 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. - ISSN 0732-183X. - 35:12(2017), pp. 1281-1287. [10.1200/JCO.2016.69.4844]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2852826
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