A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small cell lung cancer
Mené sur 119 patients atteints d'un cancer métastatique du poumon non à petites cellules, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'ajout d'iniparib à un traitement combinant gemcitabine et cisplatine
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/m², days 1/8) and cisplatin (75 mg/m², day 1) with (GCI) or without (GC) iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for 6 cycles. The primary endpoint 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 : 119 patients were randomized (39 GC, 80 GCI). More GCI patients were male (80% GCI, 67% GC) and had PS 0 (61% GCI, 49% GC). The ORR was 25.6% (95%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 months (95%CI, 2.8-5.6) with GC and 5.7 months (95%CI, 4.6-6.6) with GCI (95%CI, 0.56-1.40). Median OS was 8.5 months (95%CI, 5.5 to not reached) with GC, and 12.0 months (95%CI, 8.9-17.1) with GCI (HR 0.78, 95%CI, 0.48-1.27). More GCI patients received second-line treatment (51% GC; 68% GCI). Toxicity was similar in the two arms. Grade 3-4 toxicities included asthenia (28% GC, 8% GCI), nausea (3% GC, 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.
Annals of Oncology 2014