Tumeurs avec réarrangement de ALK : étude de phase III (PROFILE 1014) comparant en première ligne crizotinib contre pémétrexed et cisplatine/carboplatine.

Présentation au sujet: "Tumeurs avec réarrangement de ALK : étude de phase III (PROFILE 1014) comparant en première ligne crizotinib contre pémétrexed et cisplatine/carboplatine."— Transcription de la présentation:

1 Tumeurs avec réarrangement de ALK : étude de phase III (PROFILE 1014) comparant en première ligne crizotinib contre pémétrexed et cisplatine/carboplatine (1) Critères d’inclusion CBNPC non épidermoïde Translocation ou inversion d’ALK Non prétraités Stratification ECOG PS 0-1 vs 2 Métastases cérébrales stables Asie vs NON Asiatique n = 172 Crizotinib 250 mg x 2/j R Pémétrexed/cisplatine ou Pémétrexed/carboplatine n = 343 n = 171 Crossover crizotinib Objectif principal : SSP Objectifs secondaires RO % SG Tolérance Qualité de vie ASCO® D’après Mok T et al., abstr. 8002, actualisé

2 Tumeurs avec réarrangement de ALK : étude de phase III (PROFILE 1014) comparant en première ligne crizotinib contre pémétrexed et cisplatine/carboplatine (2) Crizotinib (n = 172) Chimiothérapie (n = 171) Âge médian 52 54 Hommes (%) 68 (40) 63 (37) Tabagisme Jamais fumeur (%) 106 (62) 112 (65) Ancien fumeur (%) 56 (33) 54 (32) Fumeur (%) 10 (6) 5 (3) Adénocarcinome (%) 158 (92) 159 (93) Métastase cérébrale (%) 45 (26) 47 (27) ECOG PS 0-1 (%) 161 (94) 163 (95) ASCO® D’après Mok T et al., abstr. 8002, actualisé

3 Tumeurs avec réarrangement de ALK : étude de phase III (PROFILE 1014) comparant en première ligne crizotinib contre pémétrexed et cisplatine/carboplatine (3) 100 Crizotinib (n = 172) Chimiothérapie (n = 172) 80 Événements 100 (58) 137 (80) 60 Médiane, mois 10,9 7,0 Probabilité de SSP HR (IC95) 0,45 (0,35-0,60) 40 p < 0,0001 20 First-line crizotinib versus pemetrexed–cisplatin or pemetrexed–carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014) Sub-category: Lung Cancer - Non-Small Cell Metastatic Category: Lung Cancer - Non-Small Cell Metastatic Meeting: 2014 ASCO Annual Meeting Abstract No: 8002 Attend this session at the 2014 ASCO Annual Meeting! Session: Lung Cancer - Non-small Cell Metastatic Type: Poster Highlights Session Time 1: Tuesday June 3, 8:00 AM to 11:00 AM Location 1: E354b Time 2: Tuesday June 3, 11:30 AM to 12:45 PM Location 2: E450 Personalize your Meeting experience with a suggested or customized itinerary! Author(s): Tony Mok, Dong-Wan Kim, Yi-Long Wu, Benjamin J. Solomon, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Jennifer Tursi, Fiona Helen Blackhall; The Chinese University of Hong Kong, Hong Kong, China; Seoul National University Hospital, Seoul, South Korea; Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH) and Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan; Florida Hospital, Orlando, FL; Vall d'Hebron University Hospital, Barcelona, Spain; Istituto Toscano Tumori, Department of Medical Oncology, Civil Hospital of Livorno, Livorno, Italy; Pfizer Oncology, Milano, Italy; The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom Abstract Disclosures Abstract: Background: The efficacy of the oral ALK inhibitor crizotinib as 1st-line treatment for advanced ALK-positive NSCLC compared with standard chemotherapy is unknown. A multicenter, randomized open-label phase III study was conducted to compare the efficacy and safety of crizotinib vs. pemetrexed–platinum chemotherapy (PPC) in this setting. Methods: Between Jan 2011 and Jul 2013, 343 pts with previously untreated advanced non-squamous ALK-positive NSCLC were randomized 1:1 to receive crizotinib 250 mg PO BID (n=172) or PPC (pemetrexed 500 mg/m2 + either cisplatin 75 mg/m2 or carboplatin AUC 5–6; all IV q3w for ≤6 cycles; n=171). Continuation of/crossover to crizotinib after PD (per independent radiologic review) was allowed for pts randomized to crizotinib or PPC, respectively. The primary endpoint was PFS. Secondary endpoints included ORR, OS, safety, and pt-reported outcomes. Results: Proportions of pts in the crizotinib and PPC treatment groups with each stratification factor were 45% and 47% Asians, 94% and 95% with ECOG PS 0/1, and 26% and 28% with previously treated brain metastases, respectively. The study met its primary objective, demonstrating superiority of crizotinib over PPC in prolonging PFS (median 10.9 vs. 7.0 mo; HR: 0.454; 95% CI: 0.346−0.596; P<0.0001). The ORR was significantly higher with crizotinib (74% vs. 45%; P<0.0001). With 68% of pts still in follow-up, a statistically significant improvement in OS was not demonstrated (HR: 0.821; 95% CI: 0.536−1.255; P=0.1804). At time of data cut-off 109 pts on PPC had crossed over to crizotinib. AEs with crizotinib and PPC were consistent with those previously reported in patients with advanced ALK-positive or unselected NSCLC, respectively. The most common all-causality AEs with crizotinib were vision disorder and GI symptoms. Conclusions: First-line crizotinib treatment showed significant improvements in PFS and ORR compared with standard chemotherapy and had an acceptable safety profile. These findings establish crizotinib as the standard of care for pts with previously untreated advanced ALK-positive non-squamous NSCLC. Clinical trial information: 5 10 15 20 25 30 35 Mois Crizotinib (n = 172) Chimiothérapie (n = 171) p RO % 74 (128) 45 (77) < 0,0001 ASCO® D’après Mok T et al., abstr. 8002, actualisé