According to research published early online in the Journal of Clinical Oncology, no clinical benefit was observed from adding sorafenib to carboplatin and paclitaxel (CP) chemotherapy as first-line treatment for non–small-cell lung cancer (NSCLC).

Researchers evaluated the efficacy and safety of sorafenib in combination with carboplatin and paclitaxel in 926 chemotherapy-naïve patients with unresectable stage IIIB or IV non–small-cell lung cancer (NSCLC). Patients were randomised to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m2 (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point of the study was overall survival (OS), which was defined as the time from random assignment until death from any cause, whilst secondary end points included progression-free survival (PFS) and tumour response. The study was terminated early after the planned interim analysis concluded that the study was highly unlikely to meet its primary end point.

The following results were reported:
• Median OS at the planned interim analysis was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HR] = 1.15; 95% CI, 0.94 to 1.41; P = 0.915).
• A pre-specified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% CI, 1.22 to 2.81).
• Patients in arm A had a median PFS of 4.6 months (95% CI, 4.3 to 5.3 months) compared with 5.4 months (95% CI, 4.4 to 5.8 months) in arm B (HR _ 0.99; 95% CI, 0.84 to 1.16; P =0.433).
• In arm A, 84% and 17% of patients reported drug-related adverse events (AEs) and drug-related serious AEs (SAEs), respectively. In arm B, drug-related AEs and SAEs were reported by 68% and 9% of patients, respectively (p<0.001 between arms for both AEs and sAEs).
• Main grade 3 or 4 sorafenib-related toxicities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhoea (3.5%).

The researchers concluded that the addition of sorafenib to CP in chemotherapy-naïve patients with advanced NSCLC failed to show clinical benefit in this large, randomised, placebo-controlled trial.