444PD - Patient-reported outcomes (PROs) in ASCEND-5: A randomized, phase 3 study of ceritinib vs chemotherapy (CT) in patients (pts) with advanced anaplas...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Cytotoxic agents
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Tony S.K. Mok
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors T.S.K. Mok1, G. Scagliotti2, T.M. Kim3, L. Crinò4, G. Liu5, C. Gridelli6, S. Novello7, K. Kiura8, A. Bearz9, O. Gautschi10, E. Felip11, M. Nishio12, D.R. Spigel13, P. Urban14, S. Deudon14, C. Zheng15, A.T. Shaw16
  • 1Clinical Oncology, Chinese University of Hong Kong, NA - Hong Kong/CN
  • 2Oncology, University of Torino, 10043 - Orbassano/IT
  • 3Internal Medicine, Seoul National University Hospital, 08080 - Seoul/KR
  • 4Medical Oncology, University Medical School of Perugia, 06129 - Perugia/IT
  • 5Medicine, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 6Medical Oncology, SG Moscati Hospital, 83100 - Avellino/IT
  • 7Department Of Oncology, University of Turin, 10043 - Turin/IT
  • 8Department Of Allergy And Respiratory Medicine (thoracic Oncology), Okayama University Hospital, 700-8558 - Okayama/JP
  • 9Division Of Medical Oncology, IRCCS-CRO, 33081 - Aviano/IT
  • 10Department Of Medicine, Medical Oncology, Cantonal Hospital Lucerne, 6000 - Luzern/CH
  • 11Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 12Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 13Medical Oncology, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 14Clinical Research, Novartis Pharma AG, CH-4002 - Basel/CH
  • 15Biostatistics, Novartis Pharma, 07936-1080 - East Hanover/US
  • 16Medical Oncology, Massachusetts General Hospital, 022114 - Boston/US

Abstract

Background

Ceritinib demonstrated robust efficacy in CRZ-pretreated pts in phase 1 and 2 studies. ASCEND-5 evaluated the efficacy, safety and PROs in pts with ALK+ non-small cell lung cancer (NSCLC) previously treated with CT and CRZ.

Methods

ALK+ NSCLC pts with prior treatment of 1 or 2 CT regimens and CRZ were randomized to oral ceritinib 750 mg/d or CT (pemetrexed [PEM] 500 mg/m2 or docetaxel [DOC] 75 mg/m2, every 21 days). PROs were assessed using the Lung Cancer Symptom Scale (LCSS), European Organization for Research and Treatment of Cancer quality of life (QoL) (QLQ-C30) and lung cancer (QLQ-LC13) questionnaires and the EuroQoL-5 Dimensions (EQ-5D) questionnaire. PROs were evaluated at baseline, cycle 2, 3, and every 2nd subsequent cycle until mo 18, after which PROs were assessed every 9 wk and at end of treatment.

Results

Of 231 pts (median age 54 y), 115 were randomized to ceritinib and 116 to CT (PEM, n = 40; DOC, n = 73; 3 not treated). Median treatment exposure was 30.3 wk for ceritinib and 6.3 wk for CT. The primary study endpoint was met; compared with CT, ceritinib showed statistically significant improvement in PFS (by blinded independent review committee). PRO compliance was high, ≥75% at most time points. A significantly longer time to definitive deterioration of lung cancer specific symptoms pain, dyspnoea and cough (LCSS, p 

Conclusions

Ceritinib exhibited a significantly greater improvement in PFS as well as lung cancer specific symptoms and overall health status vs CT in pre-treated patients with ALK+ NSCLC.

Clinical trial indentification

NCT01828112

Legal entity responsible for the study

Novartis Pharmaceutical Corporation

Funding

Novartis Pharmaceutical Corporation

Disclosure

T.S.K. Mok: Employment: CUHK Stock: Sanomics Ltd Honoraria/Research: AZ, Roche/Genentech, Pfizer, Lilly, BI, Merck Serono, MSD, Jenssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ, Acta Biosciences, Vertex, Aveo, Biodesix, BMS, GeneDecode. G. Scagliotti: Honoraria: Eli Lilly, AZ, Pfizer, Roche, Clovis Oncology Consulting/Advisory/Speaker fees: Eli Lilly Travel/Accommodation/Expenses: Bayer. L. Crinò: Honoraria: Novartis, AstraZeneca, Boehringer Consulting/Advisory: Pfizer, Novartis AstraZeneca. G. Liu: Honoraria for advisory board membership: AstraZeneca, Novartis, Roche, Pfizer. C. Gridelli: Honoraria received as advisory board member from Novartis. S. Novello: Speaker Bureau: Eli Lilly, BMS, MSD, BI, Astra Zeneca. K. Kiura: Corporate-sponsored research: Chugai, AZ, Boehringer, Daiichi-Sankyo, and Shionogi. Personal fees (including honoraria): Novartis, Chugai, Pfizer, Lilly, and Taiho E. Felip: Consulting/Advisory: Lilly, Roche, BI, BMS, Novartis. M. Nishio: Research: Novartis, Ono Pharmaceutical, Chugai Pharmaceutical, BMS, TAIHO Pharmaceutical, Eli Lilly, Pfizer, Astellas Pharma, AstraZeneca Honoraria: Pfizer, BMS, Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, TAIHO Pharmaceutical, AstraZeneca. D.R. Spigel: Consulting/Advisory: Novartis Speaker’s bureau: Novartis Travel/Expenses: Novartis. P. Urban, S. Deudon: Employment: Novartis Pharma AG. C. Zheng: Employment: Novartis Pharmaceuticals Corporation. A.T. Shaw: Honoraria: Novartis, Pfizer, Roche Consulting/advisory: Ariad, Daiichi-sankyo, EMD Serono, Genentech, Ignyta, Novartis, Pfizer, Roche, Taiho, Blueprint Medicine Research funding: Genentech/Roche, Pfizer, Novartis. All other authors have declared no conflicts of interest.

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Table: 444PD

\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Ceritinib (n = 115)CT (n = 116)P-value
LCSS median time to definitive symptom deterioration, mo (95% CI)
Composite endpoint18.0 (13.4, NE)4.4 (1.6, 8.6)