Afatinib* delivers unprecedented first line efficacy in patients with EGFR mutation positive lung cancer in registration trial

The LUX-Lung 3 Phase III results showed that lung cancer patients taking the novel compound afatinib*, an irreversible ErbB Family Blocker, as a first-line treatment, lived for almost one year before their tumour started to grow again (progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those on standard chemotherapy (pemetrexed / cisplatin). 1 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. 1

Boehringer Ingelheim’s registration trial LUX-Lung 3 is investigating the company’s front runner molecule afatinib*, and is the largest and most robust trial to date in EGFR (ErbB1) mutation positive advanced lung cancer patients. The primary endpoint was progression-free survival (PFS).

“Not only did LUX-Lung 3 meet its primary endpoint, but it also showed that afatinib*, especially in patients with the most common EGFR mutations, almost doubled the progression free survival time compared to chemotherapy.” commented Prof. James Chih-Hsin Yang, Director of the Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan and principal investigator of the LUX-Lung 3 trial. “Based on this proven efficacy in the largest and most robust registration trial, coupled with its novel mode of action, afatinib* may become one of the most valuable treatment options for this distinct patient population.”

The delay in disease progression for afatinib*-treated patients was associated with better control of life-restricting disease-related symptoms 1. More patients taking afatinib* experienced improvement of symptoms such as dyspnea (shortness of breath), cough and chest pain. Afatinib* also delayed the onset of these symptoms 1.

A standard lung cancer questionnaire to assess the quality of life of cancer patients revealed that afatinib* treatment translates into significantly improved quality of life (e.g. at work and during household activities). 1

“We are pleased to see that the first compound from our large oncology portfolio has clearly demonstrated its clinical benefit and the potential to effectively help those lung cancer patients harboring EGFR mutations.” said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “The results of the LUX-Lung 3 clinical trial are very encouraging and we strive to bring this personalised treatment to patients in need as soon as possible.”

The most common adverse events associated with afatinib* treatment were diarrhea and skin-related side effects. These adverse events were as expected with EGFR inhibition, consistent with previous studies, and were predictable, manageable and reversible 1. These rarely led to discontinuation of the treatment. 1

To further explore the potential of afatinib* as a lung cancer treatment, Boehringer Ingelheim has initiated two new trials aimed at comparing afatinib* head-to-head with targeted treatment agents. Both trials are currently recruiting patients. LUX-Lung 7 is a Phase IIb trial evaluating afatinib versus gefitinib as a first-line treatment in EGFR mutation positive NSCLC patients. LUX-Lung 8 is a Phase III trial evaluating afatinib head-to-head versus erlotinib in second-line treatment of squamous cell carcinoma of the lung.

Afatinib* is different to currently available targeted therapies in that it irreversibly blocks the ErbB Family of receptors, meaning afatinib* blocks EGFR (ErbB1) as well as the other relevant members of the ErbB Family, all of which can be involved in pathways that help tumour cells grow, migrate and metabolise. Investigation of the clinical relevance of afatinib*’s unique mode of action which could potentially lead to a greater effect on the tumour, has provided the basis for initiation of the LUX-Lung trial programme.

Full data from the trial will be presented today in a late-breaking oral presentation at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

For more details about LUX-Lung 3, including filmed expert commentary and a webcast, go to www.thewhiteroom.info

References

*Afatinib, nintedanib (BIBF 1120) and volasertib are investigational compounds. Their safety and efficacy have not yet been fully established.

1. Abstract no: LBA7500, 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. Oral Presentation at 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2012.
2. Jang, T.W. et al. 2009. EGFR and KRAS Mutations in Patients With Adenocarcinoma of the Lung. The Korean Journal of Internal Medicine, March; 24(1), pp.48–54.
3. Ferlay J et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; EPub Ahead of print.
4. Cancer Research UK. UK lung cancer incidence. CancerStats – Key Facts 2009. [Online] Available at: http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/ [Last Accessed April 2009].
5. Allen J et al. J Natl Compr Canc Netw 2008;6(3): 285-293.