1251P - Updated analysis of response and patient-reported outcomes (PRO) in two large open-label, phase III studies (LUX-Lung 3 [LL3] and LUX-Lung 6 [LL6])...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Presenter Yi-Long Wu
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors Y. Wu1, L.V. Sequist2, C. Hu3, J. Feng4, S. Lu5, Y. Huang6, M. Schuler7, T.S.K. Mok8, N. Yamamoto9, K.J. O'Byrne10, V. Hirsh11, S.L. Geater12, C. Zhou13, D. Massey14, J. Lungershausen15, J. Yang16
  • 1Medical Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 2Medical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston/US
  • 3Pulmonary And Critical Care Medicine, Xiangya Hospital, Central South University, Changsha/CN
  • 4Medical Oncology, Jiangsu Provincial Tumor Hospital, Nanjing, Jiangsu/CN
  • 5Medical Oncology, Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai/CN
  • 6Medical Oncology, Yunnan Tumor Hospital (The Third Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province/CN
  • 7Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen/DE
  • 8Clinical Oncology, The Chinese University of Hong Kong, Hong Kong/CN
  • 9Medical Oncology, Wakayama Medical University, Wakayama/CN
  • 10Medical Oncology, St James' Hospital, Dublin/IE
  • 11Oncology, McGill University, Montreal/CA
  • 12Internal Medicine, Prince of Songkla University, Songkhla/TH
  • 13Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai/CN
  • 14Medical Oncology, Boehringer Ingelheim Ltd UK, Bracknell, Berkshire/GB
  • 15Medical Oncology, Boehringer Ingelheim GmbH, Ingelheim/DE
  • 16Oncology, National Taiwan University Hospital, Taipei/TW

Abstract

Aim

A, an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling, improved progression-free survival (PFS), showed higher objective response rates (ORR), faster time to response (TTR) and favourable trends in PROs versus cisplatin/pemetrexed (LL3; 345 pts recruited globally) and cisplatin/gemcitabine (LL6; 364 Asian pts) in treatment-naïve pts with stage IIIB/IV EGFR mut positive NSCLC. We present an updated analysis of PFS, response and PRO data.

Methods

Pts were randomized 2:1 to 40 mg A or up to 6 cycles of CT. The primary endpoint was PFS; secondary endpoints included ORR and PROs. PROs were assessed by EORTC QLQ-C30 and QLQ-LC13 questionnaires from randomization until disease progression. Updated PFS, response and PRO analyses were completed at the time of primary OS analysis, during which 21 (LL3) and 23 (LL6) pts were still on A treatment.

Results

Updated PFS analysis confirmed superiority of A in both trials. ORR, TTR and PRO analyses were consistent with earlier findings. ORR was 57% [A] vs 23% [CT] in LL3; 68% [A] vs 23% [CT] in LL6. Of those with OR, pts treated with A responded faster than those treated with CT, with response reported at the time of first imaging (week 6) in 72% vs 58% in LL3 and 73% vs 57% in LL6. Worsening of cough and dyspnea was significantly delayed with A vs CT. A greater magnitude of effect on PROs with A was seen in pts with common EGFR mut.

Median time to deterioration (months) in symptoms of cough, dyspnea and pain

LL3 LL6
A C/P HR; p-value A G/C HR; p-value
All randomised Cough 27.0 8.0 0.59; 0.006 31.1 10.3 0.46; <0.001
Dyspnea 10.4 2.9 0.68; 0.013 7.7 1.7 0.53; <0.001
Pain 4.2 3.1 0.83; 0.188 6.9 3.4 0.70; 0.022
Common mutations Cough Not estimable 10.2 0.51; 0.001 31.1 Not estimable 0.43; <0.001
Dyspnea 14.5 2.7 0.54; <0.001 8.3 1.7 0.53; <0.001
Pain 4.8 3.1 0.74; 0.052 6.4 2.7 0.67; 0.016

Conclusions

In addition to significant delay in disease progression, A induces a superior and faster response in pts with EGFR mut NSCLC and leads to long-lasting control and delay in worsening of lung cancer symptoms vs CT.

Disclosure

L.V. Sequist: Uncompensated Advisory boards for: Boehringer Ingelheim, AstraZeneca, Merrimack, Novartis, Taiho; J. Feng: Corporate sponsored research for Boehringer Ingelheim; S. Lu: Advisory boards for: AstraZeneca and Boehringer Ingelheim; M. Schuler: Advisory boards for AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer Corporate sponsored research for Boehringer Ingelheim, Novartis Other substantive relationships with University Duisburg-Essen (Patents); T. Mok: Advisory boards for AZ, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, BI, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin Pharmaceutical Board of directors on IASLC Corporate sponsored research for AZ; N. Yamamoto: Other substantive relationships with TAIHO, ONO, CHUGAI, Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim; K.J. O'Byrne: Advisory Board, Travel expenses and Honoraria for: Boehringer Ingelheim; V. Hirsh: Advisory board for: Boehringer Ingelheim; C. Zhou: Advisory boards for Boehringer Ingelheim, F. Hoffmann-La Roche, Eli Lilly; D. Massey: Employee of Boehringer Ingelheim Ltd; J. Lungershausen: Employee of Boehringer Ingelheim GmbH; J. Yang: Advisory boards for Astrazeneca, Boehringer Ingelheim, Roche/Genentech, Merck Serono, Pfizer, Clovis Oncology, Novartis, Eli Lilly, Takeda, Innopharma, Bayer Corporate sponsored research for Boehringer Ingelheim. All other authors have declared no conflicts of interest.