1229PD - 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...

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Lecia Sequist
Authors L.V. Sequist1, M. Schuler2, N. Yamamoto3, K.J. O'Byrne4, V. Hirsh5, T.S.K. Mok6, J. Lungershausen7, M. Shahidi8, M. Palmer9, J. Yang10
  • 1Center For Thoracic Cancers, Massachusetts General Hospital, MA 02114 - Boston/US
  • 2Medicine, West German Cancer Center, University Duisburg-Essen, Essen/DE
  • 3Thoracic Oncology, Shizuoka Cancer Center, JP-411-8777 - Shizuoka/JP
  • 4Oncology, St James's Hospital, Dublin/IE
  • 5Oncology, McGill University Health Centre, H3A 1A1 - Montreal/CA
  • 6Department Of Clinical Oncology, The Chinese University of Hong Kong, CN- - Shatin, Hong Kong/CN
  • 7Health Economics, Boehringer Ingelheim, Ingelheim/DE
  • 8Clinical Research / Management, Boehringer Ingelheim, Bracknell/UK
  • 9Statistics, Keele University, Keele/UK
  • 10Oncology, National Taiwan University Hospital, Taipei/TW

Abstract

Background

Afatinib (A) is an oral, irreversible ErbB family blocker. LUX-Lung 3 compared A with cisplatin/pemetrexed (CP) in patients with EGFR mutation positive lung adenocarcinoma. The primary analysis demonstrated significant improvement in progression-free survival (PFS), with a median PFS of 11.1 months for A and 6.9 months for CP (HR = 0.58, p = 0.0004). Here, we present patient-reported Health-related Quality of Life (HRQoL) data.

Methods

345 patients were randomized (2:1) to receive A or CP. Symptoms and HRQoL were measured using EORTC questionnaires (QLQ-C30/LC13) at baseline and q3w until progression. Changes of ≥10 points were considered clinically significant. Analyses of cough, dyspnoea and pain symptoms were pre-specified. Time to deterioration (1st 10-point worsening from baseline) was analyzed using a stratified log rank test. Percentage improved/worsened by ≥10 points or stable was determined. Mean scores over time were estimated using longitudinal (mixed-effects growth curve) models.

Results

Compliance with questionnaires was >85% over time and all patients had low baseline symptom burden. Compared to CP, therapy with A significantly delayed time to deterioration for cough (HR = 0.60; p = 0.0072) and dyspnoea (HR = 0.68; p = 0.0145); results for pain trended toward A (HR = 0.82; p = 0.1913). A higher proportion of A-treated patients had ≥10 point improvements in cough (67% vs 60%; p = 0.2444), dyspnoea (64% vs 50%; p = 0.0103) and pain (59% vs 48%; p = 0.0513), compared to CP, particularly among patients with baseline symptoms. Mean scores over time for cough and dyspnoea also significantly favoured A. Consistent with the safety profile of A, a higher proportion of A-treated patients had significant worsening of symptoms of diarrhoea, sore mouth and dysphagia compared to CP. Reported fatigue, nausea, and vomiting were significantly worse on CP. Overall, therapy with A improved global HRQoL, physical, role and cognitive functioning compared to CP (p < 0.05).

Conclusion

In LUX-Lung 3, prolongation of PFS on A was associated with significant HRQoL improvement and delay of deterioration of lung cancer-related symptoms compared to CP.

Disclosure

L.V. Sequist: Paid consultancy/advisory relationship with: Boehringer Ingelheim, Daiichi-Sankyo, Merrimack, Clovis and Celgene; Research funding from: Boehringer Ingelheim.

M. Schuler: Paid consultancy/advisory relationship with: Boehringer Ingelheim; Research funding from: Boehringer Ingelheim; Travel support from: Lilly.

K.J. O'Byrne: Paid consultancy/advisory relationship with: Boehringer Ingelheim, Lilly Oncology; Honoraria from Boehringer Ingelheim, Lilly Oncology; Research funding from Boehringer Ingelheim; Other remuneration from Boehringer Ingelheim, Lilly Oncology.

V. Hirsh: Honoraria from the Boehringer Ingelheim Advisory Board.

T.S.K. Mok: Paid consultancy/advisory relationship with and honoraria from: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiko, Boehringer Ingelheim; Research funding from: AstraZeneca.

J. Lungershausen: Employee of Boehringer Ingelheim.

M. Shahidi: Employee of Boehringer Ingelheim.

M. Palmer: Consulting fee, honorarium, travel support, fees for reviews, and payment for writing or reviewing the manuscript via N Zero 1 Ltd; Board membership of N Zero 1 Ltd and consultancy, travel/accommodation/meeting costs unrelated to activities listed.

J.C. Yang: James Chih-Hsin Yang has received honorarium for speech and advisory roles from Astrazeneca, Roche, Pfizer, OSI. He was the advisor for Boehringer Ingelheim and Eli Lilly without payment.

All other authors have declared no conflicts of interest.