ESMO: Cisplatin-Navelbine Duo Shows Survival Edge in NSCLC

ISTANBUL, Turkey, Oct. 6 -- Cisplatin-Navelbine (vinorelbine) reduces the risk of death in fully resected non-small cell lung cancer (NSCLC) patients, French researchers reported here.

This finding emerged from a meta-analysis, presented at the European Society for Medical Oncology meeting, that included data from 1,888 patients who were enrolled in four different trials comparing adjuvant cisplatin-Navelbine to no chemotherapy.

At five years, 55.0% of the patients in the chemotherapy arm remained alive, compared with 46.1% in surgery alone arm (P=0.0007).

"The data are clinically very meaningful," said Jean-Yves Douillard, M.D., of the Centre Hospital-Universitaire Nantes, who presented the data.

The benefit of chemotherapy increased with increased stage of disease. At five years, there was no difference in survival in stage I patients, 66.8% in the cisplatin-Navelbine arm versus 65.1% in the control arm. By contrast, the difference was 12.3% in stage II patients (54.6% vs 42.3%) and 15% in the stage III patients (39.8% vs 24.9%).

"Patients with stage II or stage III really benefit from the treatment after surgery and should be treated this way," said Dr. Douillard.

The increased benefit in later stage patients may reflect the fact that systemically administered chemotherapy reduces both local and distant recurrence, and late stage patients are more likely to suffer distant relapses, said Dr. Douillard.

The current study was part of a larger one called the global Lung Adjuvant Cisplatin Evaluation (LACE) project, which compared all cisplatin regimens to resection alone. Those data, which were reported at the annual meeting of the American Society of Clinical Oncology earlier this year, showed that cisplatin combinations improved survival by 5.3% at five years.

Thus the cisplatin-Norelbine combination outperforms observation without chemotherapy, reducing the risk of death by 20% (hazard ratio=0.80, 95% confidence interval, 0.70, 0.91).

The researchers did not distinguish between stage Ia and Ib disease because only 2% of patients enrolled in the trials had stage Ia disease. Also, no study currently shows evidence for benefit with adjuvant chemotherapy in stage I disease, said Dr. Douillard.

There was no difference in likelihood of response in terms of sex, disease histology (adenocarcinoma versus squamous cell carcinoma), or age. Patients with better performance status did have better disease-free survival (p=0.05) and overall survival (p=0.07) compared to those with poor performance status.

Optimal dose of the drugs, which varied among studies, remains to be determined. They. In the Big Lung Trial (BLT) and International Adjuvant Lung Cancer Trial (IALT) patients were treated with less than 400 mg/m² of Navelbine. In the National Cancer Institute of Canada Clinical Trials Group BR.10 trial (JBR10) study, patients received 400 mg/m², and in Adjuvant Navelbine International Trialist Association (ANITA) dosing was scheduled at more than 400 mg/m² of Navelbine per day.

The median overall dose received, however, was 225 mg/m² Navelbine. Similarly the dose varied for cisplatin ranging between 240 mg/m² in BLT to 400 mg/m² in ANITA and JBR10. The median dosed delivered was 300 mg/m².