Alexis B Cortot1, Clarisse Audigier-Valette2, Olivier Molinier3, Sylvestre Le Moulec4, Fabrice Barlesi5, Gérard Zalcman6, Patrick Dumont7, Damien Pouessel8, Claire Poulet9, Clara Fontaine-Delaruelle10, Sandrine Hiret11, Adrien Dixmier12, Patrick-Aldo Renault13, Catherine Becht14, Olivier Raffy15, Charles Dayen16, Julien Mazieres17, Eric Pichon18, Alexandra Langlais19, Franck Morin20, Denis Moro-Sibilot21, Benjamin Besse22. 1. Univ. Lille, CHU Lille, Thoracic Oncology Dept, CNRS, Inserm, Institut Pasteur de Lille, UMR9020 - UMR-S 1277, Canther, F-59000, Lille, France. Electronic address: alexis.cortot@chru-lille.fr. 2. Service de Pneumologie, CHITS Sainte Musse, Toulon, France. Electronic address: clarisse.audigier-valette@ch-toulon.fr. 3. Service des Maladies Respiratoires, Centre Hospitalier Général, Le Mans, France. Electronic address: omolinier@ch-lemans.fr. 4. Service de Pneumologie, Institut Bergonié, Bordeaux, France. Electronic address: s.le-moulec@bordeaux.unicancer.fr. 5. Aix Marseille University, Assistance Public Hôpitaux de Marseille. Multidisciplinary Oncology & Therapeutic Innovations Dpt, Marseille, France. Electronic address: fabrice.barlesi@ap-hm.fr. 6. Service D'oncologieThoracique, Hopital Bichat Claude Bernard, Paris, France. Electronic address: gerard.zalcman@aphp.fr. 7. Centre Hospitalier, Chauny, France. Electronic address: dr.dumont@ch-chauny.fr. 8. Service D'Oncologie Médicale, Hôpital Saint-Louis, Paris, France. Electronic address: pouessel.damien@iuct-oncopole.fr. 9. Service de Pneumologie, CHU - Groupe Hospitalier Sud, Amiens, France. Electronic address: poulet.claire@chu-amiens.fr. 10. Centre Hospitalier Universitaire Lyon Sud, Pierre Bénite, France. Electronic address: clara.fontaine-delaruelle@chu-lyon.fr. 11. Institut de Cancérologie de L'Ouest - René Gauducheau-Saint Herblain, France. Electronic address: sandrine.hiret@ico.unicancer.fr. 12. Service de Pneumologie, Centre Hospitalier Régional, Orléans, France. Electronic address: adrien.dixmier@chr-orleans.fr. 13. Service de Pneumologie, Centre Hospitalier, Pau, France. Electronic address: aldo.renault@ch-pau.fr. 14. Oncologie Médicale, Clinique de Clémentville, Montpellier, France. Electronic address: catherine.becht@laposte.net. 15. Service de Pneumologie, CH Louis Pasteur, Chartres, France. Electronic address: raffy.olivier@neuf.fr. 16. Service de Pneumologie, Centre Hospitalier, Saint Quentin, France. Electronic address: c.dayen@ch-stquentin.fr. 17. Service de Pneumologie, Hôpital Larrey, Toulouse, France. Electronic address: mazieres.j@chu-toulouse.fr. 18. Service de Pneumologie, CHRU Bretonneau, Tours, France. Electronic address: e.pichon@chu-tours.fr. 19. Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France. Electronic address: alexandra.langlais@ifct.fr. 20. Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France. Electronic address: franck.morin@ifct.fr. 21. Intergroupe Francophone de Cancérologie Thoracique (IFCT), Paris, France; Thoracic Oncology Unit, PTV, CHU Grenoble-Alpes CS10217, 38043, Grenoble, France. Electronic address: DMoro-Sibilot@chu-grenoble.fr. 22. Cancer Medecine Department, Gustave Roussy, Villejuif, France; Paris-Saclay University, Orsay, France. Electronic address: benjamin.besse@gustaveroussy.fr.
Abstract
PURPOSE: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC). METHODS: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671. RESULTS:One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44-0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8-30·3) and 5·5% (95% CI: 0·0-11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patients died due to treatment-related AEs (1·8% in each group). CONCLUSION:Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01763671.
RCT Entities:
PURPOSE: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC). METHODS: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m2 of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m2) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671. RESULTS: One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5·4 months versus 3·9 months, adjusted hazard ratio (HR) 0·61 (95% confidence interval [CI]: 0·44-0·86); p = 0·005]. Objective response rates (ORRs) were 22·5% (95% CI: 14·8-30·3) and 5·5% (95% CI: 0·0-11·5) (p = 0·006), respectively. Median overall survivals were similar (adjusted HR 1·17; p = 0·50). Crossover occurred in 21 of 55 (38·2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19·3% versus 45·4%), neuropathy (8·3% versus 0·0%) and hypertension (7·3% versus 0·0%). Three patientsdied due to treatment-related AEs (1·8% in each group). CONCLUSION: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01763671.