Lung cancer patients who have already been treated with the EGFR inhibitors Erlotinib or Gefitinib seem to gain further benefits in terms of progression-free survival and tumor shrinkage when treated with the new drug Afatinib.

The LUX-Lung 1 trial of Afatinib included 585 patients with lung adenocarcinoma whose cancer had progressed after chemotherapy and Erlotinib or Gefitinib.

The participants were randomly assigned to either best supportive care plus a placebo, or supportive care plus Afatinib, which is an irreversible inhibitor of two cancer-associated cell surface molecules, epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER2 ).

While the results showed no significant difference in overall survival between the two groups, patients who were given Afatinib saw disease progression delayed and were more likely to experience tumor shrinkage.

Median overall survival was 10.78 months for patients who received supportive care plus Afatinib, compared to 11.96 months for those receiving supportive care plus placebo.

Median progression-free survival was 3.3 months for patients administered Afatinib, compared to 1.1 month in the placebo group. The disease control rate after 8 weeks of therapy was 58% in the Afatinib arm, and 19% for the placebo arm.
The investigator analysis saw an overall response rate of 11% in Afatinib patients, compared to 0.5% for those receiving placebo plus best supportive care.

The study has shown that adding Afatinib to best supportive care improved progression free but not overall survival as compared to placebo and best supportive care in patients with advanced non-small cell lung cancer who previously received chemotherapy and either Gefitinib or Erlotinib.
Afatinib has induced objective regressions in a population with no or limited treatment options, delayed progression of cancer and was associated with some improvement in cancer-related symptoms.
The lack of survival benefit may be related to the likely high enrichment of the trial population by EGFR mutated patients with outstanding median survival times of around 11 months in the 3rd/4th line setting. Such survivals highlight the intrinsic good prognosis of EGFR-mutated NSCLC patients.

Source: ESMO Meeting, 2010

XagenaMedicine2010


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