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Non-small Cell Lung Cancer

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Presentation on theme: "Non-small Cell Lung Cancer"— Presentation transcript:

1 Non-small Cell Lung Cancer
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-Ares1, F. de Marinis2, M. Dediu3, M. Thomas4, J.L. Pujol5, P. Bidoli6, O. Molinier7, T.P. Sahoo8, E. Laack9, M. Reck10, J. Corral1, S. Melemed11, W. John11, N. Chouaki12, A. H. Zimmermann11, C. Visseren-Grul13, C. Gridelli14 1University Hospital - Virgen del Rocio, Seville, Spain; 2San Camillo - Forlanini Hospital, Rome, Italy; 3Institute of Oncology, Bucharest, Romania; 4Clinic for Thoracic Diseases at University Hospital Heidelberg, Heidelberg, Germany; 5Montpellier Academic Hospital, Montpellier, France; 6Medical Oncology Unit, S. Gerardo Hospital, Monza, Italy; 7Le Mans Regional Hospital, Le Mans, France; 8Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal, India; 9University Hospital Hamburg-Eppendorf, Germany; 10Hospital Grosshansdorf, Grosshansdorf, Germany; 11Eli Lilly and Company, Indianapolis, IN, USA; 12Eli Lilly and Company, Suresnes, Hauts de Seine, France ; 13Eli Lilly and Company, Houten, The Netherlands; 14San 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 2Azzoli CG et al. J Clin Oncol 2009; 27:6251–6266 3Scagliotti GV et al. J Clin Oncol 2008;26: ; 4Ciuleanu T et al. Lancet 2009;374:

3 PARAMOUNT: Study Design
Study Treatment Period Progression Induction Therapy (4 cycles) Maintenance Therapy (Until PD) 21 to 42 Days 500 mg/m2 Pemetrexed + 75 mg/m2 Cisplatin, d1, q21d CR, PR, SD PD Placebo + BSC, d1, q21d 500 mg/m2 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) Primary objective: progression-free survival (PFS) Secondary Objectives: OS, RR, QOL, Resource utilization & adverse events

4 PARAMOUNT: Investigator Assessed PFS (from Maintenance)
Pem + BSC Placebo + BSC Pemetrexed: median =4.1 mos ( ) Placebo: median =2.8 mos ( ) Log-rank P= Unadjusted HR: 0.62 ( ) Patients at Risk Pem + BSC N=359 132 57 21 4 Placebo + BSC N=180 52 15 5

5 PARAMOUNT: Independently Reviewed PFS (from Maintenance)
88% of patients were independently reviewed (472/539) Pem + BSC Placebo + BSC Pemetrexed: median =3.9 mos ( ) Placebo: median =2.6 mos ( ) Log-rank P=0.0002 Unadjusted HR: 0.64 ( ) Patients at Risk Pem + BSC N=316 128 56 16 4 Placebo + BSC N=156 44 13 7

6 PARAMOUNT: Investigator Assessed PFS (from Induction)
Pem + BSC Placebo + BSC Pem: median = 6.90 ( ) Placebo: median = 5.59 ( ) Log Rank p< Unadjusted HR : 0.59 ( ) Patients at Risk Pem + BSC N=359 320 141 59 24 4 Placebo + BSC N=180 157 51 14 5

7 PARAMOUNT: Post-discontinuation therapy (PDT-eligible patients)
Pemetrexed (N=200) n (%) Placebo (N=122) P Value Patients with PDT 116 (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) 0.580 Vinorelbine 8 (4) 2 (2) Bevacizumab 3 (2) 1 (0.8) 1.00 Cisplatin Other 13 (7) 6 (5) -- 2 (1.0) Postdiscontinuation therapy (PDT) was administered at the discretion of the investigator. A similar percentage of patients on both arms received PDT (pemetrexed: 58%; placebo: 64%; P=0.348). There were 217 patients who did not receive PDT at the time of this analysis; 179 (82%) of the 217 patients were still receiving maintenance treatment at this time. The PDT selections were well balanced between the treatment arms. Note: In the table in this slide, percentages are based on the population of patients who received postdiscontinuation therapy, plus any other patients who were alive 30 days after study treatment discontinuation (defined as “PDT eligible patients”). Note also: Systemic therapies administered to ≤1% of patients on both arms are summarized under “Other”. These therapies included: carboplatin, pemetrexed, BIBF 1120, paclitaxel, placebo, acetylsalicylic acid (aspirin), aflibercept, cyclophosphamide, gefitinib, ifosfamide, vinflunine, and other antineoplastic agents.

8 PARAMOUNT: CTCAEs Grade 3/4 Drug-related Toxicities (Randomized Patients)
Grade 3/4 Event Pemetrexed N=359 (%) Placebo N=180 Fatigue* 4.2 0.6 Anemia* 4.5 Neutropenia* 3.6 Leukopenia 1.7 Anorexia 0.3 Nausea Neuropathy-sensory Mucositis/stomatitis ALT (SGPT) *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 NSCLC1 The study was fully powered for OS; this will be reported when data are mature 1Ciuleanu T, et al. Lancet 2009;374:

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