Outcomes of Phase II Clinical Trials with Single-Agent Therapies in Advanced/Metastatic Non-Small Cell Lung Cancer Published between 2000 and 2009
A partir d'une revue de la littérature publiée entre 2000 et 2009 sur des essais de phase II ayant évalué des monothérapies chez des patients atteints d'un cancer du poumon non à petites cellules de stade avancé ou métastatique (143 essais portant sur un total de 7 701 patients), cette étude identifie des paramètres permettant de prédire la réponse thérapeutique
Purpose: We analyzed the outcomes of single-agent phase II trials in non-small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity. Exoerimental Design: Data on response rate (RR), progression-free survival (PFS), and overall survival (OS) from all English-language, single-agent phase II trials in advanced/metastatic NSCLC indexed by PubMed (January 2000 through December 2009) were abstracted. Results: A total of 143 single-agent phase II trials (7,701 patients) were identified. The median RR was 10%, PFS 2.8 months, and OS 7.6 months. RR and PFS correlated with OS (r=0.46, p<0.001, r=0.52, p<0.001, respectively) and RR correlated with PFS (r=0.61, p<0.001). Treatment arms enriched for patients with molecular targets had a higher median RR (48.8% vs. 9.7%, p=0.005), longer median PFS (6 vs. 2.8 months, p=0.005), and OS (11.3 vs. 7.5 months, p=0.05) compared to those with unselected patients. In multivariate analysis, only studies enriched for patients with molecular targets or including drugs that eventually gained FDA/EMEA approval were associated with a higher RR, and longer PFS/OS. Conclusions: In phase II trials in NSCLC, RR and PFS correlated with OS. Studies enriched for patients with putative molecular drug targets were associated with higher therapeutic benefit compared to those with unselected populations.