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Background: This study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m(2) given over 90 min i.v. and l-leucovorin 200 mg/m(2) given over 120 min on day 1, followed by 5-FU 400 mg/m(2) bolus and then 2400 mg/m2 infused over 46 h) in untreated metastatic colorectal cancer (mCRC). Patients and methods: In this multicentre, phase I, open-label, dose-finding trial, FOLFIRI was administered every 2 weeks. Two sunitinib regimens were explored: Schedule 4/2 (4 weeks on, 2 weeks off; 37.5 and 50 mg/day) and continuous daily dosing (CDD; 37.5 and 25 mg/day). Dose-limiting toxic toxicities (DLTs) were evaluated during weeks 1-6. Efficacy was a secondary objective. Results: Thirty-seven patients were enrolled. The 37.5 mg/day Schedule 4/2 cohort had zero of six DLTs, was expanded by 15 patients and declared the MTD. The MTD was exceeded at all other sunitinib doses and schedules; DLTs included febrile neutropenia (n = 1), grade 4 neutropenia (n = 4) and grade 3 deep vein thrombosis with grade 4 neutropenia (n = 1). At the MTD, non-haematologic grade 3/4 adverse events with a frequency of >10% were diarrhoea, vomiting and lethargy, and the objective response rate was 57.9% (95% confidence interval 33.5-79.7). Conclusions: The MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37.5 mg/day on Schedule 4/2. CDD of sunitinib at 37.5 or 25 mg/day plus FOLFIRI was not feasible.

Aim: The main objective of our analysis was to compare patient-reported symptom and global QOL improvement and worsening rates between crizotinib and platinum based chemotherapy in treatment naive patients with advanced ALK-positive NSCLC in PROFILE 1014 study (Pfizer; NCT01154140). Methods: Patients in the ongoing PROFILE 1014 study were randomized to crizotinib (250 mg PO bid; n= 172) or chemotherapy (pemetrexed 500 mg/m2 + either cisplatin 75 mg/m2 or carboplatin AUC 5–6; all IV q3w for ≤6 cycles; n= 171). Patient-reported outcomes were assessed at baseline, day 7 and day 15 of cycle 1, day 1 of subsequent 3-week cycles and end of treatment using EORTC QLQ-C30 and lung can¬cer module QLQ-LC13. Higher scores (range 0 - 100) indicated higher symptom severity or better functioning/QOL. A clinically meaningful change was defined as a ≥10-point change from baseline. The percentage of patients classified as having improved (≥10-point increase for functioning/QOL scales / ≥ 10-point reduction for symptoms in average of change from baseline scores across cycles for a patient) or worsened (≥10-point reduction for functioning / ≥ 10-point increase for symptoms in average of change from baseline scores across cycles) was examined and compared between treatment groups using chi-square tests. Results: Completion rates at baseline were ≥95% in each group and scores were balanced. A significantly (p Conclusions: Treatment with crizotinib led to higher improvement rates in global QOL, physical functioning and key lung cancer symptoms compared with chemotherapy. Disclosure: F. Blackhall: Advisory boards: Pfizer; E. Felip: Advisory boards: Boehringer-Ingelheim, Novartis, Roche, BMS, Lilly; F. Cappuzzo: Advisory boards: Pfizer; D.W. Kim: Advisory boards: Pfizer, Novartis; Y. Wu: Other substantive relationships (Honoraria): Roche, AstraZeneca, Eli Lilly; B. Solomon: Advisory boards: Pfizer, Novartis, Roche, Clovis Oncology, AstraZeneca, Merck, BMS, 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; T. Mok: Advisory boards: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, AVEO, Pfizer, Taiho, Boehringer-Ingelheim, Novartis, GSK Biologicals, Clovis Oncology, Amgen, Janssen, BioMarin; Board of directors: IASLC; Corporate-sponsored research: AstraZeneca. All other authors have declared no conflicts of interest.

Aim: 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. Methods: 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. Results: 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 Conclusions: 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-naive advanced ALK-positive non-squamous NSCLC. Disclosure: 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.

Aim: The prognostic stratification of poor risk mRCC patients in the era of targeted therapy represents an unmet medical need. We analyzed, individually, each prognostic factor included in modified Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng criteria to investigate their prognostic relevance in poor risk mRCC patients and proposed a model to stratify poor risk patients into 3 separate subgroups. Methods: Data were collected from 20 Italian and 2 Spanish centers. Overall survival (OS) was estimated using Kaplan-Meier method. Hemoglobin, Performance Status, Thrombocytosis, Neutrophilia, Number of metastatic sites, Time from diagnosis to treatment, LDH and Hypercalcemia, according to modified MSKCC and Heng criteria, were included in the Cox analysis. Results: 239 (151 males; 205 clear cell) poor risk mRCC pts were enrolled according to, at least, three of MSKCC, or modified MSKCC or Heng criteria. 233 pts were treated with a first line therapy (56 pts with temsirolimus, 163 pts with tyrosine kinase inhibitors (TKI), 14 pts with other agents); 101 pts with a second line (50 everolimus, 49 TKI, 2 other agents) and 31 pts with a third line ( 4 everolimus; 20 TKI, 7 other agents). Only Hemoglobin (13 vs 8 months; p = 0.005), Performance Status (14 vs 7 months; p = 0.002), and Time from diagnosis to treatment (22 vs. 8 months; p Conclusions: This is the first study that identifies three different prognostic subgroups among poor risk RCC patients. Kaplan Meier survival curves of each subgroup will be presented during the meeting. Disclosure: All authors have declared no conflicts of interest.