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    Alimta Alimta Presentation Transcript

    • Alimta ® (Pemetrexed) as a Second-Line Treatment for Patients with Non-Small Cell Lung Cancer Presentation to the Oncologic Drugs Advisory Committee Paolo Paoletti, MD Vice President Clinical Research Oncology 27 July 2004 Eli Lilly and Company Version: Modified by: Date: 10/13/03 ID : 001 Content Owner: Informational SubCat: SubSubCat Paoletti Status: Core StudyID
    • Agenda Version: Modified by: ; Date: ID : 002 Content Owner: Informational Agenda SubSubCat Paoletti Status: Core StudyID
      • Introduction Paolo Paoletti, MD
        • Objectives of Presentation Vice President, Clinical Research Oncology, Eli Lilly and Company
      • Background Frances A. Shepherd, MD
        • 2nd-Line Treatment of NSCLC Professor of Medicine, University of Toronto Scott Taylor Chair in Lung Cancer Research, President IASLC
      • Alimta Development Roy Herbst, MD, PhD Chief, Thoracic Oncology, University of Texas M.D. Anderson Cancer Center
      • Clinical Efficacy Paul A. Bunn, Jr., MD
        • Pivotal Study JMEI Director, University of Colorado Cancer Center
      • Safety Profile Richard J. Gralla, MD
        • Pivotal Study JMEI President, Multinational Association of
      • Supportive Care in Cancer, Director IASLC
      • Conclusions Paul A. Bunn, Jr., MD
    • List of External Experts Robert Allen, MD University of Colorado, United States Donald Berry, PhD University of Texas, MD Anderson, United States Hilary Calvert, MD University of Newcastle, United Kingdom Scott Emerson, MD, PhD University of Washington, United States Nasser Hanna, MD Indiana University, United States Axel Hanauske, MD, PhD Allgemeines Krankenhaus St Georg, Hamburg, Germany Christian Manegold, MD Thorax Klinik, Heidelberg, Germany Giorgio Scagliotti, MD University of Turin, Torino, Italy ID : 141 Content Owner: Informational List of Experts SubSubCat Paoletti Status: Core StudyID
    • Lilly Team ID : 152 Content Owner: Informational List of Experts SubSubCat Paoletti Status: Core StudyID Medical William John, MD Louis Kayitalire, MD Astra Liepa, PharmD Binh Nguyen, MD, PhD Paolo Paoletti, MD Regulatory Affairs Jeffrey Ferguson Anne Kehely, MD Debasish Roychowdhury, MD John Worzalla Statistics Clet Niyikiza, PhD Sofia Paul, PhD Patrick Peterson, PhD Jim Symanowski, PhD Non-Clinical Studies Ajai Chaudhary, PhD Victor Chen, PhD Vijay Reddy, PhD, DVM Rebecca Wrishko, PhD
    • Objective of Presentation
      • Provide evidence that Alimta is effective and safe. Lilly intends to show that given its superior safety, Alimta has a better risk-benefit profile than docetaxel (Taxotere ® ) and provides clinical benefit to patients with non-small cell lung cancer (NSCLC).
        • Alimta i s a novel, effective agent in the treatment of NSCLC
          • Demonstrates similar efficacy to docetaxel
          • Shows consistent results across all assessed endpoints and subgroups
          • Estimated to retain 102% of docetaxel's benefit over BSC
          • Is superior to historical BSC
        • Alimta has an excellent safety profile
          • Has a superior safety profile to docetaxel
      • Alimta offers an effective and safer option in the treatment of second-line NSCLC
      Version: Modified by: ; Date: ID : 003 Content Owner: Informational Objectives SubSubCat Paoletti Status: Core StudyID
    • Proposed Indication and Dosage Schedule
      • Alimta as a single‑agent is indicated for the treatment of patients with locally advanced or metastatic non‑small cell lung cancer (NSCLC) after prior chemotherapy
      • Dose: 500 mg/m 2 iv, 10 minutes, Day 1 of each 21-day cycle
      • Folic Acid: 350-1000 µ g orally daily; Vitamin B 12 1000 µ g im, q 3 cycles
      • Dexamethasone: 4 mg bid on d-1, d0, d+1
      ID : 450 Content Owner: Dosage and Delays Objectives SubSubCat Paoletti Status: Core StudyID
    • Development of Alimta in Second-Line Treatment of NSCLC
      • Consistent evidence of activity in seven Phase II studies
        • Single agent (3 studies)
        • In combination with platinum agents (4 studies)
        • Both in 1st and 2nd-line
      • Supplementation with Folic Acid/B 12 improved safety profile of Alimta
        • Degree of toxicity reduction was not fully characterized
      • Decision to proceed with a Phase III study (JMEI) in 2nd-line treatment of NSCLC
      ID : 176 Content Owner: Background SubCat: SubSubCat Paoletti Status: Core StudyID
    • Design of Global, Pivotal Study JMEI
      • Decision to run “Head to Head” trial of Alimta vs docetaxel
        • Global study to support global registration
        • BSC in 2nd-line NSCLC considered not feasible in US
        • Combination chemotherapy not appropriate in 2nd-line setting
        • Docetaxel only approved agent for treatment of 2nd-line NSCLC
      • Survival as a primary endpoint
        • Limited historical data on the effect of docetaxel
        • “ Pure equivalency” study would require >4000 pts
      ID : 177 Content Owner: Statistical Design SubCat: SubSubCat Paoletti Status: Core StudyID
    • Design of Global, Pivotal Study JMEI
      • Sample size of 520 patients allows for testing both superiority and non inferiority
      • Compare treatment arms by HR for survival
      • Protocol Specified:
        • Superiority
        • 10% fixed margin NI (EU regulatory)
      • Statistical Analysis Plan Specified (prior to unblinding):
        • Percent Retention of the effect of docetaxel over BSC
          • 50% retention – basis of approval for capecitabine (colorectal) and docetaxel (breast cancer)
          • Percent Retention methodology published January 2003
      ID : 157 Content Owner: Statistical Design SubCat: SubSubCat Paoletti Status: Core StudyID
      • JMEI first patient enrolled 20 March 2001
      • JMEI last patient enrolled 06 February 2002
      • Final Statistical Analysis Plan for 24 January 2003
      • JMEI approved
      • Unblinding of JMEI analysis data sets 30 January 2003
      • US fast track designation for 2nd- 23 July 2003 line treatment of NSCLC
      • US NSCLC submission 04 November 2003
      • NSCLC 2nd Line and Mesothelioma 22 June 2004 EU-CHMP positive opinion
      Alimta Second-Line Treatment of NSCLC Global Development Timeline Version: Modified by: ; Date: ID : 004 Content Owner: Timeline Submission Timeline SubSubCat Paoletti Status: Core StudyID
    • Alimta in Combination with Cisplatin is Approved in the US for Mesothelioma – 04 February 2004 MST = 12.1 mo HR: 0.77 Log rank p-value = 0.020 MST = 9.3 mo 0 5 10 15 20 25 30 100 Months 75 50 25 0 Method: Kaplan-Meier % Alive Alimta+Cis (n=226) Cis (n=222) ID : 011 Content Owner: Background Approval in Meso SubSubCat Paoletti Status: Core StudyID
    • Why Alimta Merits FDA Approval as Second-Line Treatment for NSCLC
      • Seven Alimta Phase II studies show consistent evidence of activity
      • From this large Phase III randomized study in 2nd-line NSCLC, consistently similar efficacy results compared to docetaxel:
        • All primary and secondary efficacy endpoints
        • All subgroup analyses
      • Significantly better efficacy than historical BSC
      • Alimta has a significantly better safety profile when compared with docetaxel for clinically relevant events
      • Alimta is safe and effective and offers a superior
      • benefit-to-risk profile compared to docetaxel
      Version: Modified by: ; Date: ID : 007 Content Owner: Risk-Benefit Conclusions SubCat: SubSubCat Paoletti Status: Core StudyID
    • Points for Consideration
      • Docetaxel is effective in the 2nd-line treatment of NSCLC, but its use is limited by toxicity
        • Results in the 288 patients receiving docetaxel in the JMEI trial confirms docetaxel’s survival effect and safety profile
      • The small size of the docetaxel vs BSC pivotal trial made non-inferiority designs and analyses very challenging.
      • Inevitable post study treatment may confound a survival endpoint; analysis of JMEI data suggest such a confounding effect is unlikely
      • Interpretation of the results we present must consider the whole body of evidence
      ID : 451 Content Owner: Informational Objectives SubSubCat Paoletti Status: Core StudyID
    • Non-Small Cell Lung Cancer Second-Line Treatment Version: Modified by: Date: 10/13/03 Frances A. Shepherd, MD, FRCPC Scott Taylor Chair in Lung Cancer Research, Princess Margaret Hospital Professor of Medicine, University of Toronto President, International Association for the Study of Lung Cancer ID : 013 Content Owner: NSCLC SubCat: SubSubCat Shepherd Status: Core StudyID
    • 1997 ASCO Guidelines for NSCLC “… there is no current evidence that either confirms or refutes that 2nd-line chemotherapy improves survival in … patients with advanced NSCLC.”* * Treatment Guidelines For Unresectable NSCLC. JCO 15: 2996-3019, 1997. ID : 138 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
    • Monotherapy for Previously Treated Patients With Advanced NSCLC Gemcitabine ID : 138 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID 6-11 mo. 8-21% 272 Docetaxel 4-10 mo . 0-23% 112 Paclitaxel 4-8 mo . 0-21% 201 3 mo. 0-20% 63 Vinorelbine Median Survival Overall RR N Agent
    • Study Design - TAX 317
      • NSCLC
      • Stratified by:
      • ECOG PS (0,1 vs 2)
      • Best response to prior platinum
      • (PD vs. non-PD)
      • 1 0 Objective: survival
      • No prior paclitaxel
      RANDOMIZE 317A Docetaxel 100 mg/m 2 , one-hour iv infusion on Day 1 q 21d Premedication: Dexamethasone 8 mg x 10 doses, beginning 12 hours before docetaxel By Protocol Amendment: Docetaxel 75 mg/m 2 , one-hour IV infusion on Day 1 q 21d Premedication: Dexamethasone 8 mg x 5 doses, beginning 12 hours before docetaxel 317B Best Supportive Care without chemotherapy ID : 014 Shepherd, Frances TAX 317/320 Study Design SubSubCat Shepherd Status: Core StudyID
    • Summary of Efficacy Results – TAX 317 ID : 018 Shepherd, Frances TAX 317/320 Efficacy SubSubCat Shepherd Status: Core StudyID * 44% reduction in risk of death compared to BSC — 0.010* 0.780 Log-rank p-value 12% 37% 19% One-Year Survival 4.6 mo 7.5 mo 5.9 mo Median Survival 1.6 mo 2.8 mo — TTPD — 6% 6% Partial Response BSC (n=49) Doc75 (n=55) Doc100 (n=49)
    • Survival – TAX 317B Docetaxel 75mg/m 2 vs BSC Median 7.5 mo vs. 4.6 mo Log-rank p = 0.010 1-year 37% vs. 12% Chi-square p = 0.003 Doc75 (n=55) BSC75 (n=49) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 3 6 9 12 15 18 21 Survival Time (months) Cumulative Probability ID : 016 Shepherd, Frances TAX 317/320 Efficacy SubSubCat Shepherd Status: Core StudyID
    • TAX 317B Updated Survival (Number of Prior Regimens) ID : 138 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
    • Study Design – TAX 320 R A N D O M I Z E
      • NSCLC Stratified by:
      • Best response to last platinum
      • (PD vs. non-PD)
      • ECOG PS (0,1 vs. 2)
      • 1 0 Objective: survival
      • Prior Paclitaxel allowed
      Docetaxel 100 mg/m² iv q 3wks Premedication: Dexamethasone 8 mg x 5 doses, beginning 12 hours before docetaxel Docetaxel 75 mg/m² iv q 3wks Premedication: Dexamethasone 8 mg x 5 doses, beginning 12 hours before docetaxel Vinorelbine 30 mg/m² iv Days 1, 8, 15 q 3wks - or - Ifosfamide 2 gm/m² iv (+ Mesna) Days 1, 2, 3 q 3wks Response assessment every 2 cycles ID : 017 Shepherd, Frances TAX 317/320 Study Design SubSubCat Shepherd Status: Core StudyID
    • Summary of Efficacy Results – TAX 320 ID : 015 Shepherd, Frances TAX 317/320 Efficacy SubSubCat Shepherd Status: Core StudyID * Log-rank p=0.13 ** Chi square p=0.05 19% 5.6 mo 1.8 mo 1% V/I (n=122) 32%** 21% One-Year Survival 5.7 mo* 5.5 mo Median Survival 2.0 mo 1.9 mo TTPD 7% 11% Partial Response Doc75 (n=124) Doc100 (n=124)
    • Overall Survival – TAX 320 Cumulative Probability 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Doc100 Doc75 V/I Doc75 vs. V / I Log-rank Test p= 0.12 1-Year 32% vs 19% (p = 0.05, Chi-square) Doc100 vs. V / I Log-rank Test p= 0.13 1-Year 21% vs 19% ID : 019 Shepherd, Frances TAX 317/320 Efficacy SubSubCat Shepherd Status: Core StudyID Survival Time (Mo) 0 3 6 9 12 15 18 21
    • Docetaxel Toxicities (75 mg/m 2 ) Regardless of Causality (per Label)* * Data combined from TAX 317 and TAX 320 ** Grade 4 neutropenia with fever >38 °C with iv antibiotics or hospitalization n/a = Not Applicable ID : 452 Content Owner: TAX 317/320 Objectives SubSubCat Shepherd Status: Core StudyID 6.3** n/a Febrile Neutropenia n/a 56.3 Alopecia 1.7 23.3 Neurosensory 2.8 22.7 Diarrhea 10.2 33.5 Infection 65.3 84.1 Neutropenia Grade 3/4 Any Toxicity
    • Opioid Analgesic Use – TAX 317B Change from Baseline p=ns p<0.001 p<0.001 20% 13% 5% 49% 35% 18% 0% 10% 20% 30% 40% 50% 60% Ongoing at Baseline Additional Opioid Analgesic Newly-started Opioid Analgesic Percentage of Patients Doc75 BSC75 ID : 840 Shepherd, Frances TAX 317/320 LCSS SubSubCat Shepherd Status: Core StudyID
    • Weight Loss During Treatment Percent of Patients with Weight Loss > 10% 5 % 8 % 0% 5% 10% 15% 20% 25% T75 V/I TAX 317B TAX 320 2 % 25 % 0% 5% 10% 15% 20% 25% T75 BSC75 p<0.001 p=ns ID : 138 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
    • Performance Status Evaluation Performance Status (ECOG) Cycle 1 Cycle 2 Cycle 3 Mean Across Cycles 1-3 Last Assessment TAX 317B TAX 320 Better for BSC75 Better for Doc75 Better for V/I Better for Doc75 ID : 841 Shepherd, Frances TAX 317/320 LCSS SubSubCat Shepherd Status: Core StudyID -1.0 -0.8 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 0.8 1.0 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6
      • Showed that 2nd-line chemotherapy could prolong survival in NSCLC
      • Showed that 2nd-line chemotherapy could improve performance status and symptom control in NSCLC
      • Showed that 2nd-line chemotherapy did not have a negative impact on QoL in NSCLC
      • Led to the approval of docetaxel 75 mg/m 2 for the 2nd-line treatment of NSCLC in 1999
      These Landmark Trials … ID : 092 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
    • Current ASCO Guidelines for NSCLC “ Docetaxel is recommended as 2nd-line therapy for patients with advanced or metastatic NSCLC with adequate performance status who have progressed on 1st-line platinum-based therapy.”* * ASCO Treatment of Unresectable NSCLC Guideline. JCO 22-: 330-353, 2004 ID : 089 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
    • Current Second-Line Treatment of NSCLC ID : 160 Content Owner: TAX 317/320 SubCat: SubSubCat Shepherd Status: Core StudyID
      • Patients benefit from treatment with docetaxel
      • Safer or more effective alternatives to docetaxel are needed
      • Unmet medical need
        • Performance status and toxicity of 1st-line therapy may preclude docetaxel use
        • Increased use of 1st-line docetaxel
      • No other approved options
      • There is a need for additional options in second-line treatment of NSCLC
    • Alimta Development Roy Herbst, MD, PhD Chief and Associate Professor, Thoracic Oncology, University of Texas M. D. Anderson Cancer Center Version: Modified by: Date: 10/13/03 ID : 009 Content Owner: Informational SubCat: SubSubCat Herbst Status: Core StudyID
    • Alimta (Pemetrexed) Chemical Structure ID : 203 Chen, Victor Chemical Structure Chemical Structure SubSubCat Herbst Status: Core StudyID N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H- pyrrolo[2,3-d]pyrimidin -5-yl)ethyl]benzoyl]-L-glutamic acid Alimta (Pemetrexed) Folic Acid
    • Alimta Mechanism of Action GARFT RNA & DNA Synthesis AMP GMP DHFR TS DNA Synthesis IMP PRPP + Gln 10-CHO-FH 4 5, 10-CH 2 -FH 4 FH 4 dUMP FH 2 dTMP Cell Membrane Alimta-Glu n Alimta FPGS Folate Carriers (mainly RFC) Alimta ID : 010 Content Owner: Chemical Structure, MOA Mechanism of Action SubSubCat Herbst Status: Core StudyID
    • Alimta Preclinical Results in Non Small Cell Lung Cancer ID : 142 Content Owner: Background In Vivo SubSubCat Herbst Status: Core StudyID 75 62 300 100 LX-1 Lung In vivo % Tumor Inhibition Dose Tumor Graft 156 NSCLC A549 50 NSCLC H23 60 NSCLC H460 4 NSCLC LX-1 In vitro IC 50 (nM) Tumor Cell Lines
    • First-Line NSCLC Monotherapy – Alimta and Docetaxel Efficacy * Phase III study ** Dosage amended from 600 mg/m 2 due to toxicity 1 No Vitamin Supplementation ID : 161 Content Owner: Phase 1 and 2 Approval in Meso SubSubCat Herbst Status: Core StudyID 9.2 mo 23 500 Alimta 30 Rusthoven 1 ** 16 13 25 25 16 33 Response Rate (%) 7.0 mo 100 Docetaxel 80 Gandara 7.2 mo 600 Alimta 57 Clarke 1 6.0 mo 100 Docetaxel 137 Roszkowski* NR 75 Docetaxel 20 Miller 7.4 mo 100 Docetaxel 60 Alexopoulos 10.8 mo 100 Docetaxel 41 Fossella Median Survival Dose (mg/m 2 ) Regimen N Evaluable
    • First-Line NSCLC Combination – Alimta Phase II Studies ID : 276 Kayitalire, Louis Phase 1 and 2 Combination Efficacy Herbst Status: Core StudyID * Before vitamin supplementation 29% 13.5 mo 55.8% 4.8 mo 31.6% 10.5 mo NR 5.7 mo 45% 8.9 mo 49% NR 39% 10.9 mo 50% 6.3 mo Response Rate Median Survival 1-Year Survival Median TTPD 500 Carboplatin AUC 6 500 Carboplatin AUC 6 500 Cisplatin 75 mg/m 2 500 Cisplatin 75 mg/m 2 Alimta (mg/m 2 ) Combination ( d1 q21d) 50 39 29 36 N Koshy et al. (2003) Scagliotti et al. (2003) Shepherd et al. (2001)* Manegold et al. (2000)*
    • Second-Line NSCLC Monotherapy –Alimta Phase II Study (N=79) ID : 162 Content Owner: Phase 1 and 2 Approval in Meso SubSubCat Herbst Status: Core StudyID * Before vitamin supplementation 8.9% 5.7 mo 23% 2.0 mo Response Rate Median Survival 1-Year Survival Median TTPD Relapsed < 3 mo Relapsed < 1 mo 100% 66% Smit et al. (2003)*
    • Alimta Safety Profile Version: Modified by: ; Date: Content Owner: Story-Hcy SubCat: SubSubCat Herbst Status: Core StudyID ID : 101
      • As with most antifolates, the primary toxicity is hematologic
      • Early data showed that high serum homocysteine levels – a surrogate for functional folate and/or B 12 deficiency – correlated with higher levels of toxicity
      • A decision was made to supplement all patients with folic acid and vitamin B 12
      • This resulted in decreased toxicity with no detrimental effect on efficacy
    • Or G3/4 Nonhem Tox Toxicity in Patients With and Without FA/ Vitamin B 12 Supplementation P=<0.0001 P =<0.0001 P =0.0053 P =0.026 * No toxic death reported * ID : 842 Shepherd, Frances Story-Hcy LCSS SubSubCat Herbst Status: Core StudyID
    • Summary of the Development of Alimta Version: Modified by: ; Date: Content Owner: Phase 1 and 2 SubCat: SubSubCat Herbst Status: Core StudyID ID : 101
      • Alimta has shown activity in NSCLC
        • Single agent 1st and 2nd-line
        • Combination with platinum agents in 1st-line
      • Safety of Alimta has been well characterized
        • Toxicity significantly reduced after Folic Acid / B 12
        • Very low incidence of neutropenia, febrile neutropenia, and other non-hematologic toxicities
      • A pivotal Phase III study in the treatment of 2nd-line NSCLC was indicated
    • Version: Modified by: Date: 10/13/03 Pivotal Study JMEI Randomized Phase III Study of Alimta vs Docetaxel in Patients with Locally Advanced or Metastatic NSCLC Previously Treated with Chemotherapy Paul A. Bunn, Jr., MD Grohne/Stapp Professor & Director, University of Colorado Cancer Center Executive Director, International Association for the Study of Lung Cancer Content Owner: Informational SubCat: SubSubCat Bunn Status: Core StudyID ID : 100
    • Outline of Presentation
      • Study Design
      • Patient Characteristics
      • Survival
      • Survival Analysis
        • Alimta vs docetaxel
        • Alimta vs historical BSC
      • Other Secondary Endpoints
      • Toxicity
      • Conclusion
      ID : 453 Content Owner: Informational Objectives SubSubCat Bunn Status: Core StudyID
    • Phase III Study of Alimta vs Docetaxel in 2nd-Line NSCLC Alimta (N=283) 500 mg/m 2 iv q3wks (folic acid 350-1000 µg daily + vitamin B 12 1000 µ g q 9wks; dexamethasone 4 mg bid on d-1, d0, d+1)
      • Balanced for:
      • ECOG PS 0/1 vs 2
      • Stage III vs IV
      • No. of prior regimens (1 or 2)
      • Best response to prior chemo
      • Time since last chemo (< or > 3 mo)
      • Prior platinum
      • Prior taxane
      • Homocysteine level (< or > 12 µ m)
      • Center
      Version: Modified by: ; Date: Content Owner: Statistical Design SubCat: SubSubCat Bunn Status: Core StudyID ID : 101 RANDOMI ZE Docetaxel (N=288) 75 mg/m 2 iv q3wks (dexamethasone 8 mg bid on d-1, d0, d+1)
      • Primary Endpoint:
          • Overall Survival HR
      • Major Secondary Endpoints:
          • Progression-Free Survival
          • Time to Progressive Disease
          • Tumor Response Rate
          • Toxicity
          • Lung Cancer Symptom Scale
      JMEI: Endpoints Version: Modified by: ; Date: Content Owner: Statistical Design SubCat: SubSubCat Bunn Status: Core StudyID ID : 102
    • Definition of Populations Intent to treat (ITT): All randomized patients, regardless of therapy. Primarily used for efficacy analyses. Randomized and Treated (RT): All randomized patients who received at least one dose of chemotherapy. Primarily used for safety analyses. ID : 454 Content Owner: Statistical Design Objectives SubSubCat Bunn Status: Core StudyID
      • Inclusion Criteria
        • Histologic/cytologic Stage III or IV NSCLC
        • Only 1 regimen for metastatic disease
        • ECOG PS 0-2
        • Adequate end organ function
      • Exclusion Criteria
        • Symptomatic brain metastasis
        • Grade 3 or 4 peripheral neuropathy
        • Weight loss > 10% over previous 6 weeks
        • Uncontrolled pleural effusions
        • Prior docetaxel therapy
      JMEI: Inclusion/Exclusion Criteria Version: Modified by: ; Date: ID : 105 Content Owner: Statistical Design SubCat: SubSubCat Bunn Status: Core StudyID
    • JMEI: Baseline Characteristics (ITT) ID : 106 Content Owner: Baseline Charact SubCat: SubSubCat Bunn Status: Core StudyID 49.3% 32.3% 54.4% 27.6% Histology Adenocarcinoma Squamous 74.7% 74.9% Stage IV 12.4% 11.4% ECOG PS 2 Percent of Patients 68.9% 71.4% Homocysteine levels <12 μm 57 (28-87) 75.3% 59 (22-81) 68.6% Median Age, years (range) Male Docetaxel (N=288) Alimta (N=283)
    • JMEI: Baseline Characteristics (ITT) ID : 455 Content Owner: Baseline Charact SubCat: SubSubCat Bunn Status: Core StudyID Percent of Patients 89.9% 92.6% Prior Platinum 27.8% 25.8% Prior Taxane 48.1% 50.4% < 3 mo since Last Chemo 36.5% 35.6% Best Response to Prior Chemo CR/PR Docetaxel (N=288) Alimta (N=283)
    • JMEI: Treatment Delivered (RT) ID : 107 Content Owner: Dosage and Delays SubCat: SubSubCat Bunn Status: Core StudyID * p<0.001 17.8% 19.8% Dose Delays 5.6% 1.2% Dose Reductions* 139 136 Patients Received > 4 Cycles 12 18 No Treatment Delivered (ITT-RT) 94.4% 96.6% Planned Dose Intensity 4 (1-14) 4 (1-20) No. Cycles, Median (range) Docetaxel (N=276) Alimta (N=265)
    • JMEI: Survival (ITT) MST 8.3 mo 1-yr OS: 29.7% MST 7.9 mo 1-yr OS: 29.7% MST = median survival time * Test of superiority and 10% non-inferiority not statistically significant 0 18 15 12 9 6 3 21 1.00 0.75 0.50 0.25 0.00 Survival Distribution Months HR 0.99 95% CI of HR (0.82, 1.20*) Alimta (N=283) Docetaxel (N=288) ID : 108 Content Owner: Overall Survival SubCat: SubSubCat Bunn Status: Core StudyID
    • Interpreting the Efficacy of Alimta Relative to BSC
      • Retention method was used to estimate the percent of docetaxel benefit over BSC retained by Alimta
        • 95% CI for %-retention pre-specified in the Analysis Plan
        • Based on TAX 317B (75 mg/m 2 docetaxel randomized vs BSC)
        • Accounts for variability (sample size) in TAX 317B and JMEI
        • Allows for a survival comparison of Alimta to historical BSC
        • Assumes a reasonable comparability of TAX 317B and JMEI
      ID : 165 Content Owner: Overall Survival Analysis Plan SubSubCat Bunn Status: Core StudyID
    • Patient Demographics for TAX 317 and JMEI ID : 487 Paul, Sofia Baseline Charact. SubCat: SubSubCat Bunn Status: Core StudyID 12% 15% Performance status (2) 75% 79% Stage IV 6% 25% Number of prior chemo (2) 91% 27% 64% 72% 58 JMEI (N=571) TAX 317 Data (N=204) 100% Prior platinum 0% Prior taxane 65% Best response to prior chemo (other than CR/PR) 67% Male 61 Median Age, years
    • JMEI: Survival with TAX 317 (ITT) ID : 108 Content Owner: Overall Survival SubCat: SubSubCat Bunn Status: Core StudyID HR (Alimta vs BSC) 0.55 95% CI: 0.33, 0.90 p-value= 0.019 JMEI Docetaxel (N=288) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 3 6 9 12 15 18 21 Survival Time (months) Cumulative Probability TAX 317 Docetaxel (N=55) JMEI Alimta (N=276) TAX 317B BSC (N=49)
    • JMEI: Overall Survival ID : 164 Content Owner: Overall Survival Analysis Plan SubSubCat Bunn Status: Core StudyID * Percent retention based on TAX 317 (B) results JMEI 95% CI 0% 0.70 1.40 0.82 157% 52% 1.20 102% Percent Retention* Hazard Ratio Alimta vs docetaxel 0.99 Alimta superior to BSC* 1.33 78% 1.11 Alimta within 10% margin of docetaxel Alimta retains >50% of docetaxel benefit* 1.21 1.00 Alimta superior to docetaxel
    • JMEI: Overall Survival ID : 808 Content Owner: Overall Survival SubCat: SubSubCat Bunn Status: Core StudyID RT Population ITT Population 50% retention non-inferiority test based on point estimate of control effect (HR docetaxel/BSC = 0.555) (52%, 157%) 0.047 206 Alimta (N=283) 95% CI of estimated percent of efficacy retained by Alimta NI p-value for testing 50% retention Events (58%, 168%) 0.036 198 192 203 Docetaxel (N=276) Alimta (N=265) Docetaxel (N=288)
    • JMEI: Stepwise Cox Multiple Regression Survival Model Version: Modified by: ; Date:
      • Stage of disease (III vs IV)
      • Performances status (0 or 1 vs 2)
      • Time since last chemotherapy (  3 vs  3 mo)
      • Best response to prior chemotherapy (CR/PR vs SD vs PD/unknown)
      • Prior taxane use (Yes vs No)
      • Prior platinum use (Yes vs No)
      • Prior chemotherapies (1 vs 2)
      ID : 120 Content Owner: Statistical Design SubCat: SubSubCat Bunn Status: Core StudyID
    • JMEI: Factors Predictive of Survival Version: Modified by: ; Date: Cox Multiple Regression Model ID : 121 Content Owner: Survival Other Subs SubCat: SubSubCat Bunn Status: Core StudyID 0.026 0.004 < 0.001 p-value 0.77 (0.60, 0.97) Stage of Disease (III over IV) 0.74 (0.60, 0.90) Time since last chemotherapy (  3 mo over  3 mo) 0.25 (0.19, 0.34) Performance Status (0 – 1 over 2) HR (95% CI for HR) Variable
    • JMEI: Adjusted Overall Survival (ITT) ID : 168 Content Owner: Overall Survival Analysis Plan SubSubCat Bunn Status: Core StudyID 0.70 1.40 0.76 JMEI 95% CI Hazard Ratio 0.93 1.13 HR 0.93 95% CI of HR (0.76, 1.13) p-value vs 1.11 = 0.051 Alimta within 10% margin of docetaxel 3.6 days 1.11
    • JMEI: Survival Analyses for Key Subgroups Version: Modified by: ; Date: ID : 075 Peterson, Patrick Statistical Results Subgroup Survival SubSubCat Bunn Status: Core StudyID No treatment differences within subgroups 0.92 1.06 0.99 1.01 0.75 1.00 1.03 0.97 0. 74 1.03 HR 0.90 0.97 0.89 1.11 0.73 0.99 0.97 0.84 0.91 0.95 Adjusted HR 50 No Prior Platinum 286 > 3 mo since last chemo 277 < 3 mo since last chemo 427 Stage IV 144 Stage III 64 Performance Status 2 474 Performance Status 0 or 1 418 153 No Prior Taxane Prior Taxane 521 Prior Platinum N Evaluable
      • Primary Endpoint:
          • Overall Survival HR
      • Major Secondary Endpoints:
          • Progression-Free Survival (PFS)
          • Time to Progressive Disease (TTPD)
          • Tumor Response Rate
          • Toxicity
          • Lung Cancer Symptom Scale
      JMEI: Endpoints Version: Modified by: ; Date: ID : 114 Content Owner: JMEI Stats and Design SubCat: SubSubCat Bunn Status: Core StudyID
    • JMEI: Progression-Free Survival (ITT) MPFS = median progression-free survival Alimta (N=283) Docetaxel (N=288) ID : 113 Content Owner: Secondary Efficacy SubCat: SubSubCat Bunn Status: Core StudyID HR 0.97 95% CI of HR (0.82, 1.16) MPFS = 2.9 mo MPFS = 2.9 mo 0 18 15 12 9 6 3 21 1.00 0.75 0.50 0.25 0.00 Survival Distribution Months
    • JMEI: Time to Disease Progression (ITT) ID : 095 Peterson, Patrick Secondary Efficacy TTPD KM Bunn Status: Core StudyID 1.00 0.75 0.50 0.25 0.00 Survival Distribution Factor 0 18 15 12 9 6 3 21 Alimta (N=283) Docetaxel (N=288) Months MTTPD = 3.4 mo MTTPD = 3.5 mo HR 0.97 95% CI of HR (0.80, 1.17) MTTPD = median time to disease progression
    • JMEI: Post Study Chemotherapy Received (RT) Version: Modified by: ; Date: ID : 047 Content Owner: Survival by Post Study Post Study Chemo SubSubCat Bunn Status: Core StudyID 34 (12.3) 22 (8.4) Other chemo 5 (1.9) 17 (6.4) 6 (2.3) 4 (1.5) 85 (32.1) 15 (5.4) 9 (3.4) Platinum 11 (4.0) Docetaxel 3 (1.1) Paclitaxel 25 (9.1) Vinorelbine 32 (11.6) Gemcitabine 21 (7.6) Gefitinib 107 (38.8) 126 (47.5)  1 Chemotherapy No. of Patients in Each Arm (%) Docetaxel (N=276) Alimta (N=265) Type
    • JMEI: Survival by Post Study Chemotherapy Group (RT) Version: Modified by: ; Date: ID : 048 Content Owner: Survival by Post Study Post Study Chemo SubSubCat Bunn Status: Core StudyID 10.8 mo 107 9.8 mo 126 Any post-study chemo 96 11 169 Docetaxel (N=276) 10.6 mo 9.6 mo 6.2 mo MS 11.2 mo 41 Other chemotherapy 10.1 mo 85 Post-study docetaxel therapy 5.0 mo 139 No post-study chemo MS Alimta (N=265) Patient Population
    • JMEI: Post Progression Survival Alimta (N=213) Docetaxel (N=208) HR 1.01 95% CI of HR (0.81, 1.27) MST 4.5 mo MST 4.5 mo 1.00 0.75 0.50 0.25 0.00 Survival Distribution Factor 0 15 12.5 10 7.5 5 2.5 17.5 20 Post Progression Survival
    • JMEI: Response Rates Version: Modified by: ; Date: 0 10 20 30 40 50 9.1% (CI 5.9, 13.2) 8.8% (CI 5.7, 12.8) 45.8% (CI 39.7, 52.1) 46.4% (CI 40.3, 52.5) Complete and partial response Stable Disease Alimta (n=264) Docetaxel (n=274) ID : 111 Content Owner: Secondary Efficacy SubCat: SubSubCat Bunn Status: Core StudyID
    • Statistically Significant Grade 3/4 CTC Toxicities Regardless of Causality (RT) ID : 701 Content Owner: Lab Tox and Feb Neut. Objectives SubSubCat Bunn Status: Core StudyID 0.034 0.4 2.6 ALT <0.001 5.8 0 Infect w Gr 3/4 Neutropenia <0.001 42.4 11.3 Alopecia (all grades) 0.006 4.0 0.4 Diarrhea <0.001 12.7 1.9 Febrile Neutropenia Percent of Patients 40.2 Docetaxel (N=276) 5.3 Alimta (N=265) <0.001 Neutropenia p-value Toxicity
    • Benefit of Alimta in Second-Line NSCLC
      • Survival of Alimta compared to docetaxel:
        • Overall survival is similar
        • Retains 102% of docetaxel benefit (over BSC)
        • Internal consistency within subgroups
        • No cross-over or other post-study chemotherapy effect
      • Superior survival to historical BSC
      • Similar response rate to docetaxel
      • Similar PFS and TTPD to docetaxel
      • Superior safety profile to docetaxel
      ID : 169 Content Owner: Risk-Benefit Conclusion Analysis Plan SubSubCat Bunn Status: Core StudyID
    • JMEI Randomized Trial: Alimta vs Docetaxel in Second-Line NSCLC Version: Modified by: Date: 10/13/03 ID : 088 Content Owner: NSCLC SubCat: SubSubCat Zhang Status: Core StudyID Safety Results and Patient Reported Outcomes Richard J. Gralla, MD President, Multinational Association of Supportive Care in Cancer
      • Primary Endpoint:
          • Survival
      • Major Secondary Endpoints:
          • Progression-Free Survival
          • Time to Progressive Disease
          • Tumor Response Rate
          • Toxicity
          • Lung Cancer Symptom Scale
      JMEI: Endpoints Version: Modified by: ; Date: ID : 114 Content Owner: JMEI Stats and Design SubCat: SubSubCat Zhang Status: Core StudyID
    • Patient Reported Outcomes: Evaluation Methods in the JMEI Trial
      • Lung Cancer Symptom Scale (LCSS)
          • Well validated with published psychometrics *
          • Patient (9 items) & Observer (6 items) forms
          • Developed for clinical trials and patient management
          • Used in many randomized, multicenter trials in lung cancer
      • Evaluation
          • Patients completed the instrument weekly while on trial
          • 85% of patients adequately completed the PRO evaluation
      * Reference: Hollen et al Cancer , 1994. ID : 081 Content Owner: JMEI Safety QoL SubSubCat Gralla Status: Core StudyID
    • Maximum Symptom Improvement from Baseline for Patients with CR/PR vs SD vs PD ASBI = Average Symptom Burden Index De Marinis et al, Proc ASCO 2004 ID : 175 Content Owner: QoL Symptom Improvement SubSubCat Gralla Status: Core StudyID
    • Maximum Symptom Improvement from Baseline for Patients with CR/PR + SD All between-arm comparisons were not statistically significant ASBI = Average Symptom Burden Index De Marinis et al, Proc ASCO 2004 ID : 173 Content Owner: QoL Symptom Improvement SubSubCat Gralla Status: Core StudyID
      • Primary Endpoint:
          • Survival
      • Major Secondary Endpoints:
          • Progression-Free Survival
          • Time to Progressive Disease
          • Tumor Response Rate
          • Toxicity
          • Lung Cancer Symptom Scale
      JMEI: Endpoints Version: Modified by: ; Date: ID : 114 Content Owner: JMEI Stats and Design SubCat: SubSubCat Zhang Status: Core StudyID
    • Docetaxel Toxicities (75 mg/m 2 ) Regardless of Causality (per Label)* * Data combined from TAX 317 and TAX 320 ** ANC Grade 4 with fever >38 °C with iv antibiotics and/or hospitalization ID : 702 Content Owner: Lab Tox, CTC, Hosp Objectives SubSubCat Gralla Status: Core StudyID 1.7 26.1 Stomatitis 2.8 21.6 Vomiting 5.1 33.5 Nausea 10.2 33.5 Infection - 56.3 Alopecia 0.6 19.9 Rash 2.8 35.5 Fluid Retention 2.8 5.7 Hypersensitivity 1.7 23.3 Neurosensory 2.8 22.7 Diarrhea 18.2 52.8 Asthenia 6.3** - Febrile Neutropenia 65.3 84.1 Neutropenia Grade 3/4 Any Toxicity
    • JMEI: Adverse Events (RT) Version: Modified by: ; Date: ID : 058 Content Owner: Non-Lab Adverse Events SubSubCat Gralla Status: Core StudyID * On-study or within 30 days of discontinuation Percent of Patients On-study deaths*: 98.6 85.9 43.5 23.9 14.5 1.8 Docetaxel (N=276) 97.7 78.1 37.4 10.2 11.7 1.1 Alimta (N=265) NS 0.025 Patients with 1 or more TEAE: Regardless of causality Drug-related NS <0.001 Patients with 1 or more SAE: Regardless of causality Drug-related NS NS Regardless of causality Drug-related p-value Event
    • JMEI: Summary of Deaths Number of patients ID : 640 Content Owner: Non Lab SubCat: SubSubCat Gralla Status: Core StudyID * On-study or within 30 days of discontinuation 40 9 26 5 Docetaxel 31 10 18 3 Alimta On-Study* 0.818 Other 0.374 0.276 0.725 p-value Total Study disease related Study drug related Deaths
    • JMEI: Adverse Events (RT) NCI Common Toxicity Criteria v2 – Example: Neutropenia ID : 138 Content Owner: Lab Tox and Feb Neut SubCat: SubSubCat Gralla Status: Core StudyID Very High < 500 Grade 4 Moderate > 500 – 1000 Grade 3 Very Low > 1000 < 1500 Grade 2 None > 1500 < 2000 Grade 1 Risk / Impact Neutrophils/mm3
    • JMEI: Grade 3/4 Lab Toxicities (NCI-CTC) Regardless of Drug Causality (RT) Version: Modified by: ; Date: ID : 060 Content Owner: Lab Tox and Feb. Neut. Lab Tox SubSubCat Gralla Status: Core StudyID <0.001 40.2 5.3 Neutropenia <0.001 12.7 1.9 Febrile Neutropenia <0.001 5.8 0 Infection with Gr 3/4 Neutropenia Percent of Patients — 0.0 0.8 Bilirubin 6.2 0.7 0.0 0.4 0.4 Docetaxel (N=276) 7.5 1.9 0.0 2.6 1.1 Alimta (N=265) 0.610 0.277 1.0 0.034 0.364 Anemia Thrombocytopenia Creatinine ALT AST p-value Toxicity
    • JMEI: Gr 3/4 Non-Lab Toxicities (NCI-CTC) Regardless of Drug Causality (RT) Version: Modified by: ; Date: ID : 062 Content Owner: Non-Lab Toxicities Non-Lab Tox SubSubCat Gralla Status: Core StudyID 1.0 1.1 1.1 Stomatitis 0.817 16.7 15.8 Fatigue <0.001 42.4 11.3 Alopecia (all grades) 1.0 0.0 0.0 Rash 1.0 1.4 1.5 Vomiting 0.006 4.0 0.4 Diarrhea 0.466 2.5 3.8 Nausea 1.0 0.4 0.4 Fluid Retention Percent of Patients 0.365 9.8 7.5 Neurosensory 0.062 1.8 0.0 Hypersensitivity Docetaxel (N=276) Alimta (N=265) p-value Toxicity
    • JMEI: Lab Toxicities (NCI-CTC) Regardless of Drug Causality (RT) ID : 059 Content Owner: Lab Tox and Feb. Neut. Lab Tox SubSubCat Zhang Status: Core StudyID Percent of Patients 34.1 30.4 25.0 23.9 Docetaxel (N=276) <0.001 <0.001 0.288 0.620 p-value 5.3 All Grade 4 18.1 All Grade 3 29.4 All Grade 2 26 All Grade 1 Alimta (N=265) Toxicity
    • JMEI: Transfusions and Growth Factors (RT) Version: Modified by: ; Date: ID : 066 Content Owner: Lab Tox and Feb. Neut. Transfusions SubSubCat Gralla Status: Core StudyID Percent of Patients <0.001 19.2 2.6 G-CSF/GM-CSF 0.169 10.1 6.8 Erythropoietin 0.108 11.6 16.6 Red Blood Cell Transfusions p-value Docetaxel (N=276) Alimta (N=265)
    • JMEI: Non-Lab Toxicities Regardless of Drug Causality (RT) ID : 061 Content Owner: Non-Lab Toxicities Non-Lab Tox SubSubCat Gralla Status: Core StudyID Percent of Patients 0.020 22.5 14.3 All Grade 4 0.060 68.1 60.0 All Grade 3 >0.999 93.8 93.6 All Grade 2 0.165 92.0 95.1 All Grade 1 p-value Docetaxel (N=276) Alimta (N=265) Toxicity
    • JMEI: Hospitalizations (RT) Version: Modified by: ; Date: ID : 063 Content Owner: Non-Lab Toxicities Hospitalizations SubSubCat Gralla Status: Core StudyID All drug-related hospitalization Percent of Patients 0.092 10.5 6.4 Due to other drug-related AEs <0.001 <0.001 21.7 13.4 7.2 1.5 Any drug-related hospitalization Due to febrile neutropenia 0.032 40.6 31.7 > 1 Hospitalization due to AE 0.345 52.9 48.7 Any Hospitalizations p-value Docetaxel (N=276) Alimta (N=265)
    • Toxicity-Free (Any Grade 4) Survival Curve ID : 177 Content Owner: Risk Benefit Conclusions Clinical Benefit SubSubCat Gralla Status: Core StudyID Survival Distribution Function 0.00 0.25 0.50 0.75 1.00 Toxicity Free Survival Time (Months) 0.0 2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 Alimta (n=265) Docetaxel (n=276) MTFS 7.5 months; 1yr TFS 27.8% MTFS 2.3 months; 1 yr TFS 16.0% HR 0.57 95% CI of HR (0.47, 0.69)
    • JMEI: Safety Conclusions
      • From a safety standpoint, Alimta represents a superior treatment option in the second line treatment of NSCLC
        • Significantly less neutropenia and febrile neutropenia*
        • Significantly less alopecia and diarrhea*
        • Significantly fewer drug-related serious adverse events*
        • Fewer on-study deaths
        • Significantly fewer hospitalizations due to adverse events
        • Less use of supportive care
      * p < 0.006 ID : 086 Content Owner: Lab Tox and Feb Neut Non-Lab Tox SubSubCat Gralla Status: Core StudyID
    • Version: Modified by: Date: 10/13/03 Overall Conclusions Paul A. Bunn, Jr., MD Grohne/Stapp Prof. & Director, University of Colorado Cancer Center Exec. Director, International Association for the Study of Lung Cancer ID : 131 Content Owner: Informational SubCat: SubSubCat Bunn Status: Core StudyID
    • Treatment Options in Second-Line NSCLC
      • Alimta provides a safe and effective 2nd-line option for NSCLC patients and this is especially important because:
      • Advanced stage NSCLC patients are living longer and better lives, therefore more receive 2nd-line therapy
      • Docetaxel is the only approved compound for 2nd-line NSCLC
      • Docetaxel safety profile limits its use in 2nd-line
      Version: Modified by: ; Date: ID : 133 Content Owner: Risk-Benefit Conclusions SubCat: SubSubCat Bunn Status: Core StudyID
    • Evidence for Clinical Benefit of Alimta in 2nd-Line NSCLC (RT): Safety Version: Modified by: ; Date: ID : 180 Content Owner: Lab Tox and Feb. Neut. SubCat: SubSubCat Bunn Status: Core StudyID Alimta is safer with respect to clinically important toxicities 19.2% 2.6% G-CSF/GM-CSF 21.7% 7.2% Drug-induced AE hospitalization 42.4% 11.3% Alopecia (all grades) 4.0% 0.4% Grade 3/4 Diarrhea 12.7% 1.9% Febrile Neutropenia Docetaxel (N=276) Alimta (N=265)
    • Toxicity Comparison of Safety Database for Single Agent Alimta* Regardless of Drug Causality * With vitamin supplementation ** Single Agent ID : 846 Content Owner: Single Agent SubCat: SubSubCat Bunn Status: Core StudyID 1.1 0 Toxic Deaths 0.4 3.0 Gr. 3/4 Diarrhea 11.3 11.6 Alopecia (any grade) 7.5 2.4 Gr. 3/4 Anemia 1.9 3.7 Gr. 3/4 Platelets 1.9 1.8 Febrile Neutropenia 5.3 14.0 Gr. 3/4 Neutropenia JMEI (N=265) Other Alimta SA** (N=207)
    • Evidence for Clinical Benefit of Alimta in 2 nd Line NSCLC: Survival
      • Direct Comparison to Docetaxel
        • HR=0.99 (0.93 adjusted)
        • Median Survival (8.3 mo vs 7.9 mo)
        • One-Year Survival (29.7% vs 29.7%)
        • Internal consistency of subgroups
      • Indirect Comparison to BSC
        • Preserves at least 50% of docetaxel’s benefit over BSC
        • Superior to historical BSC
        • Consistent Alimta survival results across 1st and 2nd line trials
      Version: Modified by: ; Date: ID : 178 Content Owner: Overall Survival SubCat: SubSubCat Bunn Status: Core StudyID
    • Evidence for Clinical Benefit of Alimta in 2 nd Line NSCLC: Response, TTP
      • Direct Comparison vs. docetaxel
        • Time to Tumor Progression (3.4 mo vs 3.5 mo)
        • Progression-Free Survival (2.9 mo vs 2.9 mo)
        • Response Rate (9.1% vs 8.8%)
        • Over 50% of Alimta and docetaxel patients had improved or stable symptoms
      • Indirect Comparison to BSC
        • Comparable Overall response rates and median time to progression between Alimta trials
        • Superior response rates and TTPD
      ID : 705 Content Owner: Secondary Efficacy Objectives SubSubCat Bunn Status: Core StudyID
    • Consistency of Survival Results in Randomized Studies in 2nd-Line NSCLC 0 8 Median Survival (mo) TAX 317B N=104 TAX 320 N=248 Gridelli N=220 Camps N=254 JMEI N=571 ID : 132 Content Owner: Overall Survival SubCat: SubSubCat Bunn Status: Core StudyID JBR21 N=364 Alimta produces survival equivalent to the best docetaxel results and superior to BSC 4 2 6 Doc 75 mg/m 2 Doc 75 mg/m 2 Doc 75 m q 21d Doc 75 mg/m 2 Doc 75 m q 21d Doc 33.3m w Doc 36m w Vin/Ifos Alimta 500 mg/m 2 q 21d BSC Erlotinib 150 mg q d Placebo and BSC
    • Alimta Clinical Benefit
      • Alimta merits full approval as a single agent for the treatment of patients with locally advanced or metastatic NSCLC after prior chemotherapy based on:
        • Superior PFS and survival compared to BSC
        • Similar OR, PFS and survival compared to docetaxel
        • Superior safety profile as compared with docetaxel.
      • Making available a safer effective treatment will improve the physicians’ ability to make treatment decisions for patients with this devastating disease.
      ID : 706 Content Owner: Risk-Benefit Conclusion Objectives SubSubCat Bunn Status: Core StudyID