Details

Autor(en) / Beteiligte

• Herbst, Roy S, Prof
• Sun, Yan, MD
• Eberhardt, Wilfried EE, MD
• Germonpré, Paul, MD
• Saijo, Nagahiro, Prof
• Zhou, Caicun, MD
• Wang, Jie, MD
• Li, Longyun, MD
• Kabbinavar, Fairooz, MD
• Ichinose, Yukito, MD
• Qin, Shukui, MD
• Zhang, Li, MD
• Biesma, Bonne, MD
• Heymach, John V, MD
• Langmuir, Peter, MD
• Kennedy, Sarah J, MSc
• Tada, Hiroomi, MD
• Johnson, Bruce E, Prof

Titel

Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial

Ist Teil von

• The lancet oncology, 2010-07, Vol.11 (7), p.619-626

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Background Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC). Methods Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB–IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 intravenously every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov , number NCT00312377. Findings 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus placebo plus docetaxel (hazard ratio [HR] 0·79, 97·58% CI 0·70–0·90; p<0·0001); median PFS was 4·0 months in the vandetanib group versus 3·2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0·79, 0·62–1·00, p=0·024); median PFS was 4·6 months in the vandetanib group versus 4·2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), leukopenia (99/689 [14%] vs 77/690 [11%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel than with placebo plus docetaxel. The most common serious adverse event was febrile neutropenia (46/689 [7%] in the vandetanib group vs 38/690 [6%] in the placebo group). Interpretation The addition of vandetanib to docetaxel provides a significant improvement in PFS in patients with advanced NSCLC after progression following first-line therapy. Funding AstraZeneca.