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PARAMOUNT: Phase III Study of Maintenance Pemetrexed (Pem) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC Immediately Following Induction Treatment.

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Presentation on theme: "PARAMOUNT: Phase III Study of Maintenance Pemetrexed (Pem) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC Immediately Following Induction Treatment."— Presentation transcript:

1 PARAMOUNT: Phase III Study of Maintenance Pemetrexed (Pem) Plus Best Supportive Care (BSC) Versus Placebo Plus BSC Immediately Following Induction Treatment with Pem Plus Cisplatin for Advanced Nonsquamous Non-small Cell Lung Cancer L. G. Paz-Ares 1, F. de Marinis 2, M. Dediu 3, M. Thomas 4, J.L. Pujol 5, P. Bidoli 6, O. Molinier 7, T.P. Sahoo 8, E. Laack 9, M. Reck 10, J. Corral 1, S. Melemed 11, W. John 11, N. Chouaki 12, A. H. Zimmermann 11, C. Visseren-Grul 13, C. Gridelli 14 1 University Hospital - Virgen del Rocio, Seville, Spain; 2 San Camillo - Forlanini Hospital, Rome, Italy; 3 Institute of Oncology, Bucharest, Romania; 4 Clinic for Thoracic Diseases at University Hospital Heidelberg, Heidelberg, Germany; 5 Montpellier Academic Hospital, Montpellier, France; 6 Medical Oncology Unit, S. Gerardo Hospital, Monza, Italy; 7 Le Mans Regional Hospital, Le Mans, France; 8 Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal, India; 9 University Hospital Hamburg-Eppendorf, Germany; 10 Hospital Grosshansdorf, Grosshansdorf, Germany; 11 Eli Lilly and Company, Indianapolis, IN, USA; 12 Eli Lilly and Company, Suresnes, Hauts de Seine, France ; 13 Eli Lilly and Company, Houten, The Netherlands; 14 San Giuseppe Moscati Hospital, Avellino, Italy

2 PARAMOUNT: Background  Most patients with NSCLC have stage IIIB/IV disease at the time of diagnosis 1  Platinum-based combinations are recommended as first-line treatment 2  Pemetrexed has demonstrated efficacy in treating advanced nonsquamous NSCLC: ─ in combination with cisplatin as a first-line doublet 3 ─ as a maintenance agent following a non-pemetrexed platinum doublet 4  Maintenance therapy is used to prolong tumor response or stable disease, with a goal of improving PFS and OS  Pemetrexed maintenance has not been studied following pemetrexed-platinum induction in a phase III setting 1 2 Azzoli CG et al. J Clin Oncol 2009; 27:6251– Scagliotti GV et al. J Clin Oncol 2008;26: ; 4 Ciuleanu T et al. Lancet 2009;374:

3 PARAMOUNT: Study Design  Primary objective: progression-free survival (PFS)  Secondary Objectives: OS, RR, QOL, Resource utilization & adverse events Study Treatment Period Progression Induction Therapy (4 cycles)Maintenance Therapy (Until PD) 21 to 42 Days 500 mg/m 2 Pemetrexed + 75 mg/m 2 Cisplatin, d1, q21d CR, PR, SD PD Placebo + BSC, d1, q21d 500 mg/m 2 Pemetrexed + BSC, d1, q21d 2:1 Randomization Patients enrolled if: Nonsquamous NSCLC No prior systemic treatment for lung cancer ECOG PS 0/1 Stratified for: PS (0 vs 1) Disease stage (IIIB vs IV) prior to induction Response to induction (CR/PR vs SD)

4 PARAMOUNT: Investigator Assessed PFS (from Maintenance) Pemetrexed: median =4.1 mos ( ) Placebo: median =2.8 mos ( ) Log-rank P= Unadjusted HR: 0.62 ( ) Patients at Risk Pem + BSCN= Placebo + BSCN= Pem + BSC Placebo + BSC

5 PARAMOUNT: Independently Reviewed PFS (from Maintenance) Pemetrexed: median =3.9 mos ( ) Placebo: median =2.6 mos ( ) Log-rank P= Unadjusted HR: 0.64 ( ) Pem + BSC Placebo + BSC  88% of patients were independently reviewed (472/539) Patients at Risk Pem + BSCN= Placebo + BSC N=

6 PARAMOUNT: Investigator Assessed PFS (from Induction) Pem: median = 6.90 ( ) Placebo: median = 5.59 ( ) Log Rank p< Unadjusted HR : 0.59 ( ) Pem + BSC Placebo + BSC Patients at Risk Pem + BSCN= Placebo + BSCN=

7 Pemetrexed (N=200) n (%) Placebo (N=122) n (%) P Value Patients with PDT116 (58)78 (64) Drug Name: Erlotinib 62 (31)45 (37) Docetaxel 58 (29)43 (35) Gemcitabine 15 (8)4 (3) Investigational drug 10 (5)4 (3) Vinorelbine 8 (4)2 (2) Bevacizumab 3 (2) 1 (0.8)1.00 Cisplatin 3 (2) 1 (0.8)1.00 Other 13 (7)6 (5)-- Pemetrexed 2 (1.0)1 (0.8)1.00 PARAMOUNT: Post-discontinuation therapy (PDT-eligible patients)

8 PARAMOUNT: CTCAEs Grade 3/4 Drug- related Toxicities (Randomized Patients) Grade 3/4 Event Pemetrexed N=359 (%) Placebo N=180 (%) Fatigue * Anemia * Neutropenia * 3.60 Leukopenia1.70 Anorexia0.30 Nausea0.30 Neuropathy-sensory Mucositis/stomatitis0.30 ALT (SGPT)0.30 *Statistically significant between arms (Fisher’s exact test P≤0.05)

9 PARAMOUNT: Conclusions  PARAMOUNT met its primary endpoint by showing significantly improved PFS in patients treated with pemetrexed continuation maintenance therapy as compared to placebo  The highly significant PFS results (HR = 0.62) demonstrate that pemetrexed continuation maintenance therapy is an effective treatment for patients with advanced nonsquamous NSCLC following pemetrexed plus cisplatin induction therapy  The independent review was comprehensive (88%) in the percentage of scans and confirmed the robustness of the primary endpoint of investigator-assessed PFS  Pemetrexed had a well-tolerated safety profile, similar to the previous pemetrexed maintenance trial in NSCLC 1  The study was fully powered for OS; this will be reported when data are mature 1 Ciuleanu T, et al. Lancet 2009;374:


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