LUNG CANCER

Monoclonal Antibody Therapy Improves Outcomes for EGFR-detectable NSCLC
The FLEX trial, a randomized phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) vs. CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) demonstrated that cetuximab plus CV chemotherapy achieved superior survival over CV alone in patients with advanced EGFR-detectable NSCLC. This is the first study to demonstrate a survival benefit of an EGFR-targeted agent in combination with platinum-based chemotherapy as first-line treatment of NSCLC irrespective of histology and confirms the clinical relevance of cetuximab in NSCLC. The primary endpoint was OS. 1,688 patients, 85% EGFR(+), ECOG PS mostly 1, stage III B wet 6%/IV 94%. Results: OS (median) 11.3 months for CT + cetuximab vs. 10.1 months for CT (HR=0.87, p=0.044) and 1-year survival 47% CT + cetuximab vs. 42% for CT alone. Subgroup analysis detected difference in median OS for Caucasian compared to Asian patients (9.6 months vs. 19.5 months respectively). Side effects were as expected and manageable with acne-like rash the main cetuximab-related side effect.

Conclusion: Cetuximab added to platinum-based chemotherapy sets a new standard for the first-line treatment of patients with advanced EGFR-detectable NSCLC.
Abstract #3 R. Pirker, et al. Plenary Session-J Clin Oncol 26: 2008

Adjuvant Therapy for NSCLC: Are Patients Paying a Long-Term Price?
The long-term results of the International Adjuvant Lung Cancer Trial (IALT) evaluating adjuvant cisplatin-based chemotherapy in resected NSCLC were presented at the ASCO Annual Meeting and things have changed since the 5-year follow-up data were announced. At that update, the OS had a HR=0.86 and p=0.01 with a 3.9% absolute benefit from adjuvant chemotherapy. New data at the 8 year follow-up are OS HR=0.91, p=0.10. The DFS in the first 5 years was HR= 0.85, p=0.006 and after 5 years is now HR=0.88, p=0.02 at the 8 year follow-up. Non-lung cancer mortality HR is 1.34, p=0.06 now. The presenter stated that the chemotherapy continues to protect from recurrence for the first 5 years after surgery and the difference in the results between less than and more than 5 years of follow-up may suggest possible late adjuvant chemotherapy-related “over-mortality”. He stated that an unexpected excess of deaths after 5 years in the chemotherapy group may be due to late toxicity from chemotherapy—perhaps from etoposide (55% of patients received this drug). Reasons for the excess late mortality are unclear.
Abstract #7507 T. Le Chevalier, et al. J Clin Oncol 26: 2008