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Data from LUX-Lung 3, the largest and most robust registration trial to date** in patients with EGFR (ErbB1) mutation positive non-small cell lung cancer (NSCLC) shows that the novel compound afatinib,* an irreversible ErbB Family Blocker, leads to better and longer control and improvement of the most common lung cancer-related symptoms and better quality of life (QoL) compared to chemotherapy (pemetrexed and cisplatin), considered best-in-class for non-squamous (NSCLC).(1,2) These findings further reinforce the outstanding first-line efficacy of afatinib* in patients with EGFR mutation positive NSCLC.
Analyses of patients’ questionnaires for three pre-specified lung cancer symptoms (cough, dyspnoea and pain) showed that more afatinib*-treated patients experienced significant improvements in dyspnoea (64% versus 50%; p=0.0103), a statistical trend towards improvement in pain (59% versus 48%; p=0.0513) and numerical improvements in cough (67% vs. 60%; p=0.2444) compared to those treated with pemetrexed/ cisplatin.1 Afatinib* also significantly delayed the time to deterioration for cough (HR=0.60; p=0.007) and dyspnoea (HR=0.68; p=0.0145) versus chemotherapy.(1) Importantly, afatinib* treatment led to improved physical, role and cognitive functioning, and overall better QoL.(1)
“Lung cancer-related symptoms like fatigue, shortness of breath and pain are very distressing and have a dramatic impact on patients’ quality of life.” said Dr Matthew Peters, chair of The Global Lung Cancer Coalition. “With around 90% of advanced NSCLC patients experiencing two or more disease-related symptoms and high levels of associated psychological distress(3) it is important that we consider these endpoints when assessing the benefits of a treatment.”
Previously presented LUX-Lung 3 trial data has shown that patients taking afatinib* as a first-line treatment lived for almost one year without their tumour growing again (median progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those treated with pemetrexed/cisplatin.(4) Furthermore, NSCLC patients with tumours harbouring the two most common EGFR mutations taking afatinib* lived for well over a year without tumour progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.4 Patients with common EGFR mutations who experienced a greater PFS benefit also experienced a greater benefit in health-related QoL, symptom control and symptom improvement.(1)
“Following encouraging data presented earlier this year, the new data demonstrate that the positive progression-free survival outcomes with afatinib* also translate into additional benefits for patients in terms of quality of life and control and improvement of symptoms,” commented Dr Vera Hirsh, Associate Professor, McGill University, Department of Medical Oncology, Royal Victoria Hospital, Montreal, Canada. “This further supports the potential of this treatment option in first-line treatment of metastatic NSCLC to effectively help those patients harbouring EGFR mutations.”
Afatinib* is an irreversible ErbB Family Blocker, thus it differs from currently available targeted therapies in that it irreversibly and completely inhibits ErbB receptor signal transduction, blocking the key pathways that help tumour cells grow, migrate and metabolise.(5) This novel mode of action may lead to a distinct therapeutic benefit and has provided the basis for initiation of the LUX-Lung trial programme.(5)
References
- Abstract no: 1229PD. Sequist L. V. 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. ESMO 2012 Congress. Available at: http://abstracts.webges.com/myitinerary/session-148.html?congress=esmo2012#.UFdGtBr1LSY.gmai
- Scagliotti GV, 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(21):3543–51
- Tanaka K. et al. Impact of Dyspnea, Pain, and Fatigue on Daily Life Activities in Ambulatory Patients with Advanced Lung Cancer. Journal of Pain and Symptom Management. Journal of Pain and Symptom Management 2002, Vol. 23 No. 5.
- Abstract no: LBA7500. Yang 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. Oral Presentation at 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2012.
- Solca, F. et al. Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (Fast Forward 10 August 2012) . J Pharmacol Exp Ther 2012 343 (2).
