Overall survival (OS) results have been published in The Lancet Oncology from two independent Phase III clinical trials (LUX-Lung 3 and LUX-Lung 6) in epidermal growth factor receptor (EGFR) mutation-positive patients with metastatic non-small cell lung cancer (NSCLC).

In each trial, patients whose tumours have the most common EGFR mutation (deletion in exon 19; Del19) lived more than one year longer when treated with first-line afatinib, an irreversible ErbB Family Blocker, compared to standard chemotherapy.¹

Overall survival was a secondary endpoint.

Afatinib is the first and only EGFR targeting agent to demonstrate an overall survival benefit compared to chemotherapy in the first-line treatment of NSCLC patients with EGFR mutations.¹

“The positive overall survival results seen with afatinib in these two trials are an encouraging development for NSCLC patients with Del19 mutated tumours. No other currently existing EGFR targeted therapy has demonstrated an overall survival benefit in lung cancer patients with any type of EGFR mutation,” said Professor James Chih-Hsin Yang, Director of the Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan.

“These data further add to the body of evidence for afatinib which has previously demonstrated improvements in progression-free survival, lung cancer symptom control and quality of life in both Del19 and L858R populations, compared to chemotherapy.”

Results from both trials showed similar overall survival in the afatinib and chemotherapy arms in the overall NSCLC EGFR mutation-positive population (LUX-Lung 3: median OS 28.2 vs 28.2 months; LUX-Lung 6: median OS 23.1 vs 23.5 months), however, a significant benefit was observed in patients with the Del19 mutation.¹

For these patients, both studies individually demonstrated a significant reduction in the risk of death with first-line afatinib compared to chemotherapy.¹

That translated into a survival benefit of more than a year (LUX-Lung 3: median OS 33.3 vs 21.1 months; LUX-Lung 6: median OS 31.4 vs 18.4 months).¹

The effect was not observed for patients with L858R mutations, whose survival did not significantly differ between treatment arms in each trial.

Adverse events for afatinib in the LUX-Lung 3 and 6 trials were as expected with EGFR inhibition, and were predictable, manageable and reversible.

Diarrhoea and rash/acne were the most frequently reported side effects with afatinib therapy.^2,3

“This is the first time a targeted agent in the first-line setting has shown an overall survival benefit for NSCLC patients with the Del19 EGFR mutation,” commented Professor Gerd Stehle, Vice President Medicine Therapeutic Area Oncology, Boehringer Ingelheim.

“These data are an important scientific advancement as they clearly demonstrate that even within the EGFR mutation-positive patient group we are dealing with different molecular abnormalities that require a tailored treatment approach.”

LUX-Lung 3 (Global) and LUX-Lung 6 (Asian), two of the largest trials in this patient population, were similar in design with the exception of the platinum-based chemotherapy comparator regimen: pemetrexed/cisplatin in LUX-Lung 3 and gemcitabine/cisplatin in LUX-Lung 6.

Both studies met the primary endpoint of progression-free survival for patients whose tumours have common EGFR mutations receiving first-line afatinib.^2,3

In addition, more patients taking afatinib experienced an improvement in lung cancer-related symptoms (cough, shortness of breath, chest pain) and a significantly better quality of life, when compared with chemotherapy.⁴

References

1 Yang J, Wu Y-L, Schuler M, et al. Afatinib versus cisplatin chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015

2 Sequist L, Yang J, Yamamoto N, et al. Phase III Study of afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutations. J Clin Oncol 2013

3 Wu Y-L, Zhou C, Hu C-P, at al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. J Clin Oncol 2014

4 Yang J, Hirsh V, Schuler M, et al. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutations. J Clin Oncol 2013

Source: Boehringer Ingelheim