ASCO 2013 Abstract #8061: LUX-Lung 6

CARE Lung Cancer Faculty Canadian Perspectives from ASCO 2013

Abstract 8061: LUX-Lung 6: Patient-Reported Outcomes (PROs) From a Randomized Open-Label, Phase III Study in First-Line Advanced NSCLC Patients (Pts) Harboring Epidermal Growth Factor Receptor (EGFR) Mutations. Sarayut L. Geater, MD, RCPT

Targeted therapy with a tyrosine kinase inhibitor (TKI) against the epidermal growth factor receptor (EGFR) has become the standard of care in metastatic lung cancer for patients whose tumors harbor an EGFR receptor mutation (EGFR M+).
— CARE Lung Cancer Faculty

The use of first-generation EGFR TKIs in this setting has evolved and we have become comfortable with their use and toxicity profile. Second-generation EGFR TKIs are now available. As they form covalent bonds at the kinase domain and inhibit more members of the EGFR family, it follows that they may be superior in their efficacy. The trade-off however, may be greater toxicity.

Last year at ASCO 2012, LUX-Lung 3 was presented. Patients with stage IV adenocarcinoma EGFR M+ were randomized to receive first line afatinib versus chemotherapy with pemetrexed/cisplatin. Progression free survival (PFS) in common mutations was very impressive at 13.6 months and in all mutations at 11.1 months. The chemotherapy arm, although inferior to afatinib, was also noted at almost 7 months (6.9 months). The toxicity reported was higher than expected, especially with diarrhea where 14% of patients experienced grade 3 diarrhea. Enthusiasm for the use of first line afatinib was affected by this.

   Figure 1:  Primary endpoint: PFS LL3 & 6 superimposed.

 Figure 1: Primary endpoint: PFS LL3 & 6 superimposed.

This year at ASCO 2013, we see afatinib again used in a similar first line setting. LUX-Lung 6 randomized patients to afatinib versus chemotherapy with gemcitabine/cisplatin. PFS by independent review was 11.01 versus 5.59 months for afatinib and chemotherapy respectively. Similarly, response rates seen were 67% vs 23% respectively. Superimposing graphs for efficacy in LUX-Lung 6 and 3 are shown (Figure 1). Most importantly, the rate of grade 3 diarrhea was only 5%, making the use of first-line afatinib a much more attractive option for patients whose tumors are EGFR M+. 

In conclusion, use your best drugs upfront. Afatinib as a second-generation or as a new generation EGFR TKI looks promising in regards to both efficacy and side effect profile.