Erlotinib is a valid treatment option for patients with KRAS wild-type lung adenocarcinoma refractory to chemotherapy, study data show.
To determine the clinical significance of KRAS mutational status in response to erlotinib, Balazs Dome (Medical University of Vienna, Austria) and team conducted an open-label, multicentre, observational trial (MOTIVATE) in which patients with advanced KRAS mutation-negative lung adenocarcinoma were treated with erlotinib 150 mg daily. All patients were refractory to one or two courses of chemotherapy.
The median progression-free survival (PFS) of the 327 patients (mean age 60.8 years, 50.2% men) was 3.3 months and median overall survival (OS) was 14.4 months.
Women had significantly longer PFS and OS than men, at 3.8 versus 3.2 months and 20.5 versus 9.4 months, respectively.
Overall survival advantage was also seen for patients receiving erlotinib as a second-line treatment (n=214) compared with those receiving it as a third-line treatment (n=113), at 16.1 versus 9.4 months.
By contrast, disease stage (IIIB vs IV) and smoking status had no impact on survival. However, the researchers note that the absence of an effect of smoking on survival may be due to the low number of current smokers (n=95) in the study; the KRAS mutation is more common in smokers than nonsmokers.
However, the team did find that among the patients receiving erlotinib as a third-line therapy, never smokers lived twice as long as current smokers (11.0 vs 5.5 months).
Dome et al also observed a significant correlation between Eastern Oncology Cooperative Group Performance Status (ECOG PS) and overall survival. Specifically, the longest median OS (20.5 months) was observed in patients with ECOG PS 0-1 receiving erlotinib as second-line therapy, and in patients with ECOG PS 0, irrespective of the line of treatment (25.7 months).
Overall, three (1.2%) patients had a complete response, 51 (20.2%) had a partial response and 123 (48.8%) patients had stable disease, giving a combined disease control rate of 70.2%.
The researchers comment that ethical objections meant that they were unable to include a cohort of patients with KRAS mutation-positive non-small-cell lung cancer (NSCLC).
“However, the relatively high median PFS and OS data observed in our study do not only suggest that second or third-line erlotinib therapy confers significant benefit to patients with advanced stage KRAS [wild-type] lung adenocarcinoma but our findings also support the well-known but still ambiguous concept that KRAS mutation analysis might predict treatment non-response to [epidermal growth factor receptor-tyrosine kinase inhibitor] therapy in NSCLC”, they conclude in Lung Cancer.
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