Giotrif launch provides new option for treatment of advanced lung cancer

2 January 2014

Giotrif (afatinib) is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer in patients with activating EGFR mutation(s) who had not previously received treatment with EGFR inhibitors.

Food should not be consumed for at least 3 hours before and at least 1 hour after taking Giotrif (afatinib) for NSCLC (pictured) | SCIENCE PHOTO LIBRARY

PHARMACOLOGY

Afatinib is a ErbB family blocker which binds covalently to and irreversibly blocks signalling from all homo- and hetero-dimers formed by members of the ErbB family, including EGFR, HER2, ErbB3 and ErbB4.¹

CLINICAL STUDIES

The efficacy of EGFR genotype-directed therapy with afatinib was compared with cisplatin plus pemetrexed chemotherapy in the LUX-Lung 3 study. The phase III study included 345 patients with advanced lung adenocarcinoma and proven EGFR mutations who were randomised to receive oral afatinib 40mg once daily or intravenous cisplatin 75mg/m² plus pemetrexed 500mg/m² once every 21 days up to a maximum of six cycles.²

Tumours were assessed by a CT or MRI scan every six weeks for the first 48 weeks then every 12 weeks until disease progression or start of new anti-cancer therapy.²

Significantly longer survival

At the time of primary analysis (median follow-up of 16.4 months), progression-free survival (as assessed by independent review) was significantly prolonged in the afatinib group compared with the chemotherapy group (11.1 months versus 6.9 months, respectively [hazard ratio 0.58; 95% CI 0.43–0.78; p=0.001]). Similar findings were observed for investigator-assessed progression-free survival.²

A pre-planned analysis of patients with common EGFR mutations (n=308) showed that that the progression-free survival benefit was even greater in this population (median 13.6 months for afatinib versus 6.9 months for chemotherapy [hazard ratio 0.47; 95% CI 0.34–0.65; p=0.001).²

Significantly higher response rates were observed in the afatinib group compared with the chemotherapy group for both independent (56% versus 23%, respectively) and investigator (69% versus 44%, respectively) assessments (p=0.001 for both).²

In addition, time to deterioration of symptoms and clinically meaningful worsening of cough (hazard ratio 0.60; 95% CI 0.41–0.87; p=0.007) and dyspnoea (hazard ratio 0.68; 95% CI 0.50–0.93; p=0.01) was significantly greater in the afatinib group than in the chemotherapy group. Time to deterioration of pain was also longer in the afatinib group but this difference did not reach significance (hazard ratio 0.83; 95% CI 0.62–1.10; p=0.19).²