Afatinib* shows benefits for EGFR mutation positive non-small cell lung cancer patients across various efficacy endpoints

Data from the LUX-Lung clinical trial programme, investigating afatinib in patients with advanced non-small cell lung cancer (NSCLC), have been published in the Journal of Clinical Oncology. These data include results from the pivotal LUX-Lung 3 Phase III registration trial which show that afatinib delays tumour growth and improves disease-related symptoms and quality of life compared to standard chemotherapy, when used to treat patients with EGFR mutation positive NSCLC.

Research has shown there are many different types of lung cancer requiring a unique treatment approach to improve patient outcomes. A distinct subtype of lung cancer is EGFR mutation positive NSCLC. The prevalence of tumours harbouring EGFR mutations is between 10-15% in Caucasian and 40% in Asian NSCLC patients. Clinical trial data has shown afatinib could offer benefits to patients with this type of lung cancer.1

“A diagnosis of lung cancer can be devastating for patients and their families. As oncologists our goal is to ensure the best possible outcomes for patients through tailored treatment approaches,” said Professor James Chih-Hsin Yang, Director of the Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan and lead investigator of the LUX-Lung 3 trial. “These positive results published in the Journal of Clinical Oncology represent an advance in individualised treatment for lung cancer and emphasise the benefits afatinib could offer to lung cancer patients with EGFR mutations.”

Data published in the Journal of Clinical Oncology from the LUX-Lung clinical trial programme show the potential of afatinib to improve the lives of patients with lung cancer:

• Data from the LUX-Lung 3 trial demonstrate superiority of afatinib over chemotherapy considered best-in-class (pemetrexed/cisplatin) in EGFR-mutation positive advanced NSCLC patients.2,3,4 Patients treated with afatinib lived for almost one year (progression-free survival (PFS) of 11.1 months) before their tumour started to grow again compared to just over half a year (PFS of 6.9 months) for those treated with chemotherapy.2 Importantly, patients taking afatinib with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm. Adverse events (AEs) in LUX-Lung 3 were as expected with EGFR inhibition, consistent with previous studies, and were predictable, manageable and reversible. The most common adverse events associated with afatinib were diarrhea and skin-related side effects, which rarely led to discontinuation of treatment.2
• Additional data from the LUX-Lung 3 trial demonstrate patients taking afatinib also experienced an improvement in life-restricting lung cancer symptoms and a better quality of life (QoL) compared to those receiving standard chemotherapy treatment.3 Afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; P=0.007) and dyspnoea (HR, 0.68; P=0.015). Afatinib also showed significantly better mean scores over time in global health status/QoL (P=0 .015) and physical (P<0.001), role (P=0.004), and cognitive (P=0.007) functioning compared with chemotherapy, as measured by standard questionnaires.3
• Data from the LUX-Lung 4 trial, a Japanese single-arm Phase II trial in NSCLC patients who have progressed after EGFR-tyrosine kinase inhibitor treatment, demonstrated afatinib* treated patients experienced a median overall survival (OS) of just over a year and a half (19.0 months) and median PFS of 4.4 months.5 This highlights the efficacy of afatinib in this difficult-to-treat patient population. Adverse events were as expected with EGFR inhibition.5

“Afatinib has a novel mode of action and data has shown that it offers a clinical benefit to patients with a specific type of lung cancer, which we are further investigating in the extensive LUX-Lung clinical trial programme,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “We are delighted that the Journal of Clinical Oncology has chosen to publish data from this programme, which adds to the growing body of positive clinical evidence for afatinib.”

The LUX-Lung clinical trial programme continues to investigate afatinib in advanced NSCLC in different settings and patient populations, in order to fully evaluate the potential of this treatment option. Based on this comprehensive programme, afatinib has been submitted to regulatory bodies worldwide for the treatment of patients with locally advanced or metastatic NSCLC with EGFR mutations. Afatinib is approved in the U.S. under the U.S. brand name GILOTRIF™, and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for afatinib.

About the LUX-Lung clinical trial programme

The LUX-Lung clinical trial programme is investigating afatinib in a number of patient populations with advanced NSCLC. Two pivotal Phase III studies have recently been presented from the LUX-Lung clinical programme. LUX-Lung 6 (n=364) and LUX-Lung 3 (n=345) represent the largest, robust and consistent clinical registration trial programme in EGFR mutation positive NSCLC to date. Results from the trials were presented at the American Society of Clinical Oncology Annual Meeting in 2012 and 2013 respectively,6,7 and a further analysis of LUX-Lung 3 was presented at ESMO 2012 (European Society for Medical Oncology).8

As part of the LUX-Lung clinical trial programme, there are currently eight studies designed to investigate the use of afatinib in various settings of advanced NSCLC, including head-to-head trials with the first-wave of reversible tyrosine kinase inhibitors.

About Afatinib

Afatinib is approved by the U.S. FDA for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion for afatinib and regulatory reviews by health authorities in Asia and other countries are ongoing.

Afatinib is an irreversible ErbB Family Blocker which irreversibly blocks EGFR (ErbB1) as well as the other relevant members of the ErbB Family that are known to play a critical role in the growth and spread of the most pervasive cancers and cancers associated with high mortality. The covalent and, therefore, irreversible binding of afatinib is unlike other compounds which are reversible in that it provides a sustained, selective, and complete ErbB Family Blockade, and therefore may lead to a distinct therapeutic benefit.9,10

Afatinib is currently in Phase III clinical development in NSCLC and head & neck cancer.

About Lung Cancer

Lung cancer is one of the most common and most deadly forms of cancer in the world, it accounts for 1.6 million new cancer cases annually.11 Because of its poor prognosis, 1.38 million deaths each year are attributable to lung cancer.11 Overall, lung cancer is the cause of 18% of all cancer deaths.11 Approximately 13% of all new cases of cancer are lung cancers12 and smoking is attributed as the main cause.

References

1. Jang TW, Oak CH, Chang HK, et al. EGFR and KRAS mutations in patients with adenocarcinoma of the lung. Korean J Intern Med 2009;24: 48–54.
2. Sequist L, Yang J, Yamamoto N, et al. Phase III Stuy of Aaftinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutations. J Clin Oncol 2013;DOI: 10.1200/JCO.2012.44.2806
3. 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;DOI: 10.1200/JCO.2012.46.1764
4. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543–51.
5. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non Small-Cell Lung Cancer Who Progressed on Prior Treatment With Erlotinib, Gefitinib, or Both. J Clin Oncol 2013;DOI: 10.1200/JCO.2012.45.0981
6. Yang J, Schluer MH, Yamamoto N, et al. LUX-lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. J Clin Oncol 2012;30(18,Suppl.):Abstract LBA7500.
7. Wu, Y., MD. LUX-Lung 6: A randomized, open-label, Phase III study of afatinib (A) vs. gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts.) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung. (Abstract #8016) at American Society of Clinical Oncology, Chicago, June 2, 2013.
8. Sequist LV, Schuler M, Yamamoto N, et al. LUX-LUNG 3: symptom and health-related quality of life results from a randomized phase III study in 1st-line advanced NSCLC patients harbouring EGFR mutations. Ann Oncol 2012;23(Suppl.9):ix402 (Abstract# 1229PD).
9. Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther 2012;343:342-50.
10. Reid A, Vidal L, Shaw H, do Bono J. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). Eur J Cancer 2007;43:481-9.
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