S Novello1, B Besse2, E Felip3, F Barlesi4, J Mazieres5, G Zalcman6, J von Pawel7, M Reck8, F Cappuzzo9, D Ferry10, E Carcereny11, A Santoro12, I Garcia-Ribas13, G Scagliotti1, J-C Soria14. 1. Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy. 2. Thoracic Cancer Unit, Department of Medicine, Gustave-Roussy, Villejuif, France. Electronic address: benjamin.besse@gustaveroussy.fr. 3. Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Barcelona, Spain. 4. Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille. 5. Department of Pneumology and Allergies, CHU Toulouse Hôpital Larrey, Toulouse. 6. Department of Pneumology, CHU Côte de Nacre, Caen, France. 7. Department of Oncology, Asklepios Fachkliniken München-Gauting, Gauting. 8. Thoracic Oncology, LungenClinic Grosshansdorf, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany. 9. Department of Medical Oncology, Istituto Toscano Tumori-Ospedale Civile, Livorno, Italy. 10. Department of Oncology, New Cross Hospital, Wolverhampton, UK. 11. Department of Medical Oncology, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain. 12. Department of Medical Oncology, Humanitas Cancer Center IRCCS, Milan, Italy. 13. Oncology Division, Sanofi Aventis, Barcelona, Spain. 14. Thoracic Cancer Unit, Department of Medicine, Gustave-Roussy, Villejuif, France.
Abstract
BACKGROUND: Iniparib is a novel anticancer agent initially considered a poly (ADP-ribose) polymerase (PARP) inhibitor, but subsequently shown to act via non-selective protein modification through cysteine adducts. This randomized phase II study investigated the addition of iniparib to gemcitabine-cisplatin in metastatic non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to receive gemcitabine (1250 mg/m(2), days 1/8) and cisplatin (75 mg/m(2), day 1) with [gemcitabine/cisplatin/iniparib (GCI)] or without [gemcitabine/cisplatin (GC)] iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for six cycles. The primary end point was the overall response rate (ORR). Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. The study was not designed for formal efficacy comparison, the control arm being to benchmark results against the literature. RESULTS:One hundred and nineteen patients were randomized (39 GC and 80 GCI). More GCI patients were male (80% GCI and 67% GC) and had PS 0 (61% GCI and 49% GC). The ORR was 25.6% [95% confidence interval (CI) 13.0%-42.1%] with GC versus 20.0% (95% CI 11.9%-30.4%) with GCI, which did not allow rejection of the null hypothesis (ORR with GCI ≤20%; P = 0.545). Median PFS was 4.3 (95% CI 2.8-5.6) months with GC and 5.7 (95% CI 4.6-6.6) months with GCI (hazard ratio 0.89, 95% CI 0.56-1.40). Median OS was 8.5 (95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.9-17.1) months with GCI (hazard ratio 0.78, 95% CI 0.48-1.27). More GCI patients received second-line treatment (51% GC and 68% GCI). Toxicity was similar in the two arms. Grade 3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI), and decreased appetite (10% in each). CONCLUSIONS: Addition of iniparib to GC did not improve ORR over GC alone. The GCI safety profile was comparable to GC alone. Imbalances in PS and gender distribution may have impacted study results regarding PFS and OS. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01086254.
RCT Entities:
BACKGROUND:Iniparib is a novel anticancer agent initially considered a poly (ADP-ribose) polymerase (PARP) inhibitor, but subsequently shown to act via non-selective protein modification through cysteine adducts. This randomized phase II study investigated the addition of iniparib to gemcitabine-cisplatin in metastatic non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to receive gemcitabine (1250 mg/m(2), days 1/8) and cisplatin (75 mg/m(2), day 1) with [gemcitabine/cisplatin/iniparib (GCI)] or without [gemcitabine/cisplatin (GC)] iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for six cycles. The primary end point was the overall response rate (ORR). Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. The study was not designed for formal efficacy comparison, the control arm being to benchmark results against the literature. RESULTS: One hundred and nineteen patients were randomized (39 GC and 80 GCI). More GCIpatients were male (80% GCI and 67% GC) and had PS 0 (61% GCI and 49% GC). The ORR was 25.6% [95% confidence interval (CI) 13.0%-42.1%] with GC versus 20.0% (95% CI 11.9%-30.4%) with GCI, which did not allow rejection of the null hypothesis (ORR with GCI ≤20%; P = 0.545). Median PFS was 4.3 (95% CI 2.8-5.6) months with GC and 5.7 (95% CI 4.6-6.6) months with GCI (hazard ratio 0.89, 95% CI 0.56-1.40). Median OS was 8.5 (95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.9-17.1) months with GCI (hazard ratio 0.78, 95% CI 0.48-1.27). More GCIpatients received second-line treatment (51% GC and 68% GCI). Toxicity was similar in the two arms. Grade 3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI), and decreased appetite (10% in each). CONCLUSIONS: Addition of iniparib to GC did not improve ORR over GC alone. The GCI safety profile was comparable to GC alone. Imbalances in PS and gender distribution may have impacted study results regarding PFS and OS. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01086254.
Authors: Jaishri O Blakeley; Stuart A Grossman; Tom Mikkelsen; Myrna R Rosenfeld; David Peereboom; L Burt Nabors; Andrew S Chi; Gary Emmons; Ignacio Garcia Ribas; Jeffrey G Supko; Serena Desideri; Xiaobu Ye Journal: J Neurooncol Date: 2015-08-19 Impact factor: 4.130
Authors: Roni Nitecki; Alexander Melamed; Allison A Gockley; Jessica Floyd; Kate J Krause; Robert L Coleman; Ursula A Matulonis; Sharon H Giordano; Karen H Lu; J Alejandro Rauh-Hain Journal: Gynecol Oncol Date: 2021-03-15 Impact factor: 5.304
Authors: Jordi Remon; Benjamin Besse; Alexandra Leary; Ivan Bièche; Bastien Job; Ludovic Lacroix; Aurélie Auguste; Marjorie Mauduit; Clarisse Audigier-Valette; Judith Raimbourg; Anne Madroszyk; Stefan Michels; Mohammed Amine Bayar; Marta Jimenez; Jean-Charles Soria; Etienne Rouleau; Fabrice Barlesi Journal: JTO Clin Res Rep Date: 2020-06-11