Chemotherapy best second-line option for EGFR wild-type NSCLC

Sep 5 2013

By Joanna Lyford, Senior medwireNews Reporter

Chemotherapy is more effective than erlotinib as second-line therapy in people with advanced non-small-cell lung cancer (NSCLC) and wild-type epidermal growth factor receptor (EGFR) genotype, a randomized controlled trial has found.

Thus, in the absence of a target oncogene, the one-size-fits-all cytotoxic approach to second-line treatment of advanced NSCLC remains the best option, say the trial investigators.

EGFR tyrosine kinase inhibitors such as erlotinib are currently the first choice of therapy in EGFR-mutated tumors but the role of these drugs in wild-type tumors is less clear.

In the TArceva Italian Lung Optimization tRial (TAILOR), Italian investigators led by Massimo Broggini (Istituto di Ricerche Farmacologiche Mario Negri, Milan) compared erlotinib with chemotherapy as second-line treatment for metastatic NSCLC.

All of the 222 patients had previously received platinum-based chemotherapy and had wild-type EGFR tumors. They were randomly assigned to receive erlotinib 150 mg/day or docetaxel 35 or 75 mg/m² on days 1, 8, and 15 every 28 days.

The median duration of follow-up was 33 months, during which time 196 patients had disease progression and 187 died, Broggini and co-authors report in The Lancet Oncology.

Median overall survival was 8.2 months with docetaxel versus 5.4 months with erlotinib (adjusted hazard ratio (HR)=0.73) while median progression-free survival was 2.9 versus 2.4 months (HR=0.71); both differences were statistically significant.

Secondary efficacy endpoints followed the same pattern, with 1-year survival (39.6 vs 31.8%), progression-free survival at 6 months (27.3 vs 16.5%), and median survival after progression (3.2 vs 2.5 months) all favoring chemotherapy over erlotinib.

Also, significantly more patients had a response or achieved disease control with docetaxel than with erlotinib, and the superior efficacy of chemotherapy was consistent across patient subgroups.

Finally, safety analysis found that the frequency of adverse events was comparable in the two treatment groups; neutropenia, neurologic toxicity, alopecia, asthenia, and nausea were all more common with docetaxel than with erlotinib, while the reverse was true for skin toxicity. There was one treatment-related death in each group.

Broggini’s group concludes: “[C]hemotherapy should remain the second-line treatment of choice in patients with NSCLC with wild-type EGFR status. Docetaxel was better than erlotinib for all clinical outcomes.”

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