| General information |
| Database: | DB00856 |
| Objective: | Iniparib is a novel anticancer agent initially considered a poly (ADPribose) polymerase (PARP) inhibitor, but subsequently shown to act via nonselective protein modification through cysteine adducts. This randomizedphase II study investigated the addition of iniparib to gemcitabinecisplatin in metastatic non small cell lung cancer (non small cell lung cancer) patients. |
| Authors: | Novello S, et al |
| Title: | a phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as firstline therapy for metastatic non small cell lung cancer. |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 25139550 |
| Trial Design |
| Clinical Trial Id: | NCT01086254 |
| Agent: | iniparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gemcitabine/cisplatin (GC)] iniparib |
| Study Type: | a phase II randomized study |
| Key Patients Feature: | Patients with histologically confirmed stage IV non small cell lung cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | [gemcitabine/cisplatin/iniparib versus gemcitabine/cisplatin (GC)] iniparib |
| Treatment Info: | pts 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. |
| Primary End Point: | the overall response rate (ORR). progression free survival (PFS), overall survival (OS), and safety. |
| Secondary End Point: | NA |
| Patients Number: | 119 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 25.6% [95% confidence interval (CI) 13.0%42.1%] with GC versus 20.0% (95% CI 11.9%30.4%) with GCI |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.3 (95% CI 2.85.6) months with GC and 5.7 (95% CI 4.66.6) months with GCI (hazard ratio 0.89, 95% CI 0.561.40). |
| Median OS A vs. C: | 8.5 (95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.917.1) months with GCI (hazard ratio 0.78, 95% CI 0.481.27). |
| Adverse Event(agent arm): | Grade 1-2 hematologic toxicity was widespread, and approximately 50% of the patients had grade 3-4 events, notably neutropenia (44% GC and 37% GCI patients), including three GC patients with febrile neutropenia. Asthenia/fatigue and gastrointestinal toxicities were also frequent. Grade 3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI), decreased appetite (10% in both arms), vomiting and hypertension (8% in both arms), dyspnea (10% GC and 4% GCI), pulmonary embolism (8% GC and 6% GCI), and fatigue (5% in both arms). Differences between arms (including grade 3-4) were apparent for asthenia, nausea, dyspnea, hyponatremia, and febrile neutropenia, which were more frequent in GC patients, while pyrexia and abdominal pain were more common with GCI. |
| 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. |