Presentation is loading. Please wait.

Presentation is loading. Please wait.

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

Similar presentations


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 http://seer.cancer.gov/statfacts/html/lungb.html; 2 Azzoli CG et al. J Clin Oncol 2009; 27:6251–6266 3 Scagliotti GV et al. J Clin Oncol 2008;26:3543-51.; 4 Ciuleanu T et al. Lancet 2009;374:1432-40.

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 (3.2-4.6) Placebo: median =2.8 mos (2.6-3.1) Log-rank P=0.00006 Unadjusted HR: 0.62 (0.49-0.79) Patients at Risk Pem + BSCN=359132 57 214 0 Placebo + BSCN=180 52 15 50 0 Pem + BSC Placebo + BSC

5 PARAMOUNT: Independently Reviewed PFS (from Maintenance) Pemetrexed: median =3.9 mos (3.0-4.2) Placebo: median =2.6 mos (2.2-2.9) Log-rank P=0.0002 Unadjusted HR: 0.64 (0.51-0.81) Pem + BSC Placebo + BSC  88% of patients were independently reviewed (472/539) Patients at Risk Pem + BSCN=316128 56 164 0 Placebo + BSC N=156 44 13 70 0

6 PARAMOUNT: Investigator Assessed PFS (from Induction) Pem: median = 6.90 (6.2-7.5) Placebo: median = 5.59 (5.5-6.0) Log Rank p<0.00001 Unadjusted HR : 0.59 (0.47-0.74) Pem + BSC Placebo + BSC Patients at Risk Pem + BSCN=359320 141 5924 40 Placebo + BSCN=180 157 51 14 5 00

7 Pemetrexed (N=200) n (%) Placebo (N=122) n (%) P Value Patients with PDT116 (58)78 (64) 0.348 Drug Name: Erlotinib 62 (31)45 (37) 0.329 Docetaxel 58 (29)43 (35) 0.266 Gemcitabine 15 (8)4 (3) 0.147 Investigational drug 10 (5)4 (3) 0.580 Vinorelbine 8 (4)2 (2) 0.329 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 * 4.20.6 Anemia * 4.50.6 Neutropenia * 3.60 Leukopenia1.70 Anorexia0.30 Nausea0.30 Neuropathy-sensory 0.30.6 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;374:1432-40.


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

Similar presentations


Ads by Google