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
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
Diarrhoea and skin reactions
Afatinib was well tolerated with diarrhoea and skin-related reactions the most commonly reported adverse effects.2
- Giotrif Summaries of Product Characteristics, September 2013.
- Sequist LV et al. J Clin Oncol 2013; 31: 3327–34.
View Giotrif drug record
Further information: Boehringer Ingelheim