Abstract | BACKGROUND: 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.
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Authors | S Novello, B Besse, E Felip, F Barlesi, J Mazieres, G Zalcman, J von Pawel, M Reck, F Cappuzzo, D Ferry, E Carcereny, A Santoro, I Garcia-Ribas, G Scagliotti, J-C Soria |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 25
Issue 11
Pg. 2156-2162
(Nov 2014)
ISSN: 1569-8041 [Electronic] England |
PMID | 25139550
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]. |
Chemical References |
- Benzamides
- Deoxycytidine
- iniparib
- Cisplatin
- Gemcitabine
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Benzamides
(administration & dosage, adverse effects)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology)
- Cisplatin
(administration & dosage, adverse effects)
- Deoxycytidine
(administration & dosage, adverse effects, analogs & derivatives)
- Disease-Free Survival
- Drug-Related Side Effects and Adverse Reactions
(pathology)
- Female
- Humans
- Male
- Middle Aged
- Neoplasm Metastasis
- Treatment Outcome
- Gemcitabine
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