1225O - Overall and intracranial (IC) efficacy results and time to symptom deterioration in PROFILE 1014: 1st-line crizotinib vs pemetrexed - platinum chem...

Date 28 September 2014
Event ESMO 2014
Session NSCLC, metastatic 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Presenter Benjamin Solomon
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors B. Solomon1, E. Felip2, F.H. Blackhall3, T.S.K. Mok4, D. Kim5, Y. Wu6, K. Nakagawa7, T. Mekhail8, J. Paolini9, T. Usari9, S. Iyer10, A. Reisman11, K. Wilner12, J. Tursi9, F. Cappuzzo13
  • 1Oncology, Peter MacCallum Cancer Centre, 3002 - Melbourne/AU
  • 2Oncologia Médica, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 3Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 4Dept. Of Clinical Oncology, Chinese University of Hong Kong Prince of Wales Hospital, Hong Kong/CN
  • 5Department Of Internal Medicine, Seoul National University Hospital (SNUH)-Yongon Campus, 110-744 - Seoul/KR
  • 6Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, 510080 - Guangzhou/CN
  • 7Medical Oncology, Kinki University School of Medicine, JP-589-8511 - Osaka/JP
  • 8Medical Oncology, Florida Hospital Cancer Institute, 32804 - Orlando/US
  • 9Oncology, Pfizer, 20152 - Milano/IT
  • 10Global Outcomes Research, Pfizer Oncology, New York/US
  • 11Innovative Pharma Business, Pfizer Global, New York/US
  • 12Clinical Research, Pfizer Oncology, La Jolla/US
  • 13Oncologia, Ospedale Riuniti, Livorno/IT



Clinical outcomes (overall and IC efficacy, lung cancer symptoms) with crizotinib (criz) vs standard chemotherapy as 1st-line treatment for advanced ALK-positive NSCLC were compared in the ongoing randomized open-label phase III study PROFILE 1014 in the whole pt population and in pt subgroups.


Pts with previously untreated advanced non-squamous ALK-positive NSCLC (N = 343) were randomized 1:1 to criz 250 mg PO BID (n = 172) or PPC (pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC 5–6; all IV q3w for ≤6 cycles; n = 171). Continuation of/crossover to criz after PD (per independent radiology review [IRR]) was allowed for pts randomized to criz or PPC, respectively. The primary endpoint was PFS per IRR. Secondary endpoints included OS, IC TTP, time to deterioration in symptoms of chest pain, dyspnea, or cough (TTDS), and safety.


171 pts received criz, 91 pem − cis, 78 pem-carbo, and 3 no treatment. The study met its primary objective: criz was superior to PPC in prolonging PFS (median 10.9 vs 7.0 mo; HR: 0.45; 95% CI: 0.35 − 0.60; P < 0.0001). PFS benefit with criz was observed in most pt subgroups analysed. Median PFS was 6.9 mo with pem − cis (HR: 0.49; P < 0.0001) and 7.0 mo with pem − carbo (HR: 0.44; P < 0.0001). At time of data cutoff 120 pts had received criz after PPC; with 68% of pts in follow-up, OS differences between criz and PPC were not statistically significant (NS). The IC TTP HR for criz vs PPC was 0.60 (95% CI: 0.34 − 1.05; NS; only ∼15% of pts had IC events) and 0.45 in the 79-pt subgroup with baseline brain metastases (95% CI: 0.19 − 1.07; NS). TTDS was significantly longer with criz (median 2.1 vs 0.5 mo; HR: 0.62; P = 0.0004). The most common AEs of any cause with criz were vision disorder and GI symptoms. AEs with PPC were consistent with those previously reported in unselected NSCLC.


Crizotinib treatment showed significant improvements in PFS and TTDS vs PPC, a numerical improvement in IC TTP, and an acceptable safety profile, establishing crizotinib as the standard of care for pts with treatment-naïve advanced ALK-positive non-squamous NSCLC.


B. Solomon: Advisory boards: Pfizer, Novartis, Roche, Clovis Oncology, AstraZeneca, Merck, BMS, Lilly; E. Felip: Advisory boards: Boehringer-Ingelheim, Novartis, Roche, BMS, Lilly; F.H. Blackhall: Advisory boards: Pfizer; T.S.K. Mok: Ad boards: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer-Ingelheim, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin Pharm; Board of directors: IASLC; Corp-sponsored research: AstraZeneca; D. Kim: Advisory boards: Pfizer, Novartis; Y. Wu: Other substantive relationships (Honoraria): Roche, AstraZeneca, Eli Lilly; T. Mekhail: Advisory boards: Pfizer, Genentech, Eli Lilly, Celgene; Corporate-spnsored research: Pfizer, Genentech, Lilly, Celgene, BMS, AstraZeneca; Other substantive relationships (Speakers' Bureau): Pfizer, Genentech, Eli Lilly, Celgene; J. Paolini: Employment and stock ownership: Pfizer; T. Usari: Employment and stock ownership: Pfizer; S. Iyer: Employment, stock ownership and corporate-sponsored research: Pfizer; A. Reisman: Employment and stock ownership: Pfizer; K. Wilner: Employment, stock ownership, advisory board and corporate-sponsored research: Pfizer; J. Tursi: Employment and stock ownership: Pfizer; F. Cappuzzo: Advisory boards: Pfizer. All other authors have declared no conflicts of interest.