Randomized, Placebo-Controlled, Phase 2 Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer
Mené sur 158 patients atteints d'un cancer du poumon non à petites cellules de stade avancé ou métastatique (âge médian : 63 ans), cet essai de phase II évalue l'intérêt et l'efficacité, du point de vue de la survie sans progression, de l'ajout du véliparib à un traitement combinant carboplatine et paclitaxel
Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds, and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase 2 trial determined whether addition of veliparib to carboplatin and paclitaxel improved PFS in previously untreated advanced/metastatic non-small cell lung cancer patients. Experimental Design: Patients were randomized 2:1 to carboplatin and paclitaxel with either veliparib or placebo. Veliparib (120 mg) or placebo was given on days 1-7 of each 3-week cycle, with carboplatin (AUC=6 mg/mL/min) and paclitaxel (200 mg/m2) administered on day 3, for a maximum of 6 cycles. Results: Overall, 158 were included (median age 63 years, male 68%, squamous histology 48%). Median PFS was 5.8 months in the veliparib group vs 4.2 months in the placebo group (HR 0.72 [95% CI 0.45-1.15, P=0.17]). Median OS was 11.7 months and 9.1 months in the veliparib and placebo groups, respectively (HR 0.80 [95% CI 0.54-1.18, P=0.27]). In patients with squamous histology, median PFS (HR 0.54 [95% CI 0.26-1.12, P=0.098]) and OS (HR 0.73 [95% CI 0.43-1.24, P=0.24]) favored veliparib treatment. ORR was similar between groups (veliparib: 32.4%; placebo: 32.1%), but duration of response favored veliparib treatment (HR 0.47 [95% CI 0.16-1.42, P=0.18]). Grade 3/4 neutropenia, thrombocytopenia, and anemia were comparable between groups. Conclusions: Veliparib combination with carboplatin and paclitaxel was well tolerated and demonstrated a favorable trend in PFS and OS vs chemotherapy alone. Patients with squamous histology had the best outcomes with veliparib combination. http://clincancerres.aacrjournals.org/content/clincanres/early/2016/10/08/1078-0432.CCR-15-3069.full.pdf