1
Oncologic Drugs Oncologic Drugs Advisory Committee MeetingAdvisory Committee Meeting
NDA 21-236NDA 21-236
Cisplatin/Epinephrine Injectable Gel for Cisplatin/Epinephrine Injectable Gel for the Treatment of Squamous Cell the Treatment of Squamous Cell
Carcinoma of the Head and NeckCarcinoma of the Head and Neck
Matrix Pharmaceutical, Inc.
2
Introduction
Stephen B. Howell, M.D.Professor of Medicine
Director, Cancer Pharmacology University of California San Diego
Cancer Center
3
Presentation
Glenn Mills, M.D., Professor of Medicine, Head of Aerodigestive Malignancy Program, LSU
Summary of Risks and Benefits
Richard D. Leavitt, M.D., Senior Vice President, Medical Affairs
Clinical Study Results
Glenn Mills, M.D., Professor of Medicine, Head of Aerodigestive Malignancy Program, LSU
Current Management of Recurrent Head and Neck Cancer
Stephen B. Howell, M.D.,Professor of Medicine, UCSD
Pharmacologic Rationale; Assessment of Clinical Benefit
Stephen B. Howell, M.D., Professor of Medicine, UCSD
Discussion of Clinical Benefit Issues
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• Independent ExpertsEverett E. Vokes, M.D., John F. Ultmann Professor, Director, Section of
Hematology/Oncology, University of Chicago; Sub-Chair, Head and Neck Cancer Committee, RTOG
Barry L. Wenig, M.D., M.P.H., Professor of Otolaryngology – Head and Neck Surgery; Chief, Division of Head and Neck Surgery, Evanston Northwestern Healthcare
John Mackowiak, Ph.D., Director of Research, Center for Outcomes Research,Chapel Hill, NC
John R. Durant, M.D., Former Director, Fox Chase Cancer Center and University of Alabama Cancer Center; Chair of Clinical Cooperative Group; Past Chief Executive ASCO
Robert F. Woolson, Ph.D., Professor and Past Chair of Biostatistics, University of Iowa School of Public Health
• Matrix Pharmaceutical StaffLaurence Elias, M.D., Medical DirectorMorgan E. Stewart, Ph.D., Senior Director, Biostatistics & Data ManagementRobert Tressler, Ph.D., Senior Director, Biological Sciences
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Current Management of Recurrent Head and Neck Cancer
Glenn Mills, M.D.Professor of Medicine
Director of Clinical Research and Head of Aerodigestive Malignancy Program
Principal Investigator SWOG Feist-Weiller Cancer Center, LSUHSC-Shreveport
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Scope of the Problem
• In 2001, 50,000 new cases in the US– 20,000 relapses and 15,000 deaths
• Local disease in >50-65% who die– 7500-10,000 patients
• Risk factors – Tobacco
– Alcohol
• Concomitant diseases– Vascular disease; COPD; malnutrition
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Standard Therapy
• Early-stage disease (I, II & III)– Surgery ± radiation therapy – relapse 20-30%
• Late-stage (bulky III & IV)– Radiation ± chemotherapy – relapse 70-80%
– Local relapse a persistent problem (40-65%)
• Chemotherapy– CDDP/5FU – response rate 30-35%
– Reduced effectiveness in radiated/surgical field*
*Forastiere, A.A., et al., JCO 19:1088-95, 2001
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Locally Recurrent HNSCC
• Highly debilitating– Intractable pain
– Compromised airway
– Swallowing dysfunction
– Ulceration – cosmetic and bleeding
• Local problems may predominate even with systemic metastasis
• Median survival 4-6 months
• Quality of life is poor
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Unmet Needs in Local Recurrence
• Post XRT/surgery– Re-irradiation
• Cisplatin relapsed patients– No approved drugs
– Methotrexate, gemcitabine, and taxanes
• New agents and modalities– Better/unique activity
– Reduced toxicity
• Improve palliative care options
• Reduce risk of impending catastrophic event
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Locally Recurrent Head and Neck Cancer
Pt. 1795 Pt. 2736
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Pharmacologic Rationale and Challenges Associated with
Demonstration of Clinical Benefit
Stephen B. Howell, M.D.Professor of Medicine
Director, Cancer Pharmacology University of California San Diego
Cancer Center
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Indication Refined Since NDA Filing
• When HNSCC recurs, all patients should be considered for additional surgery, systemic chemotherapy, or re-irradiation
• CDDP/epi gel is indicated for patients with locally dominant problematic lesions– Not surgical candidates
• Lesion not resectable; resection would destroy function; surgical risk too high
– Not candidates for systemic chemotherapy• Failed multiple prior regimens; co-morbid disease
– Not candidates for re-irradiation• Risk too high; no access to radiation experts/facilities
– Refused other modalities
• Orphan indication; orphan status granted
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Product Description
Viscous injectable gel containing cisplatin and epinephrine– Cisplatin 4 mg/mL – Established role in the treatment of
HNSCC
– Epinephrine 0.1 mg/mL – Provides vasoconstriction
– Collagen gel – Ensures physically stable dispersion of cisplatin and facilitates accurate placement of drug
Cisplatin
Epinephrine
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Pharmacologic Rationale for Intratumoral Treatment
• Intratumoral CDDP/epi gel results in high tumor CDDP exposure with very little systemic exposure
• Median dose of CDDP per treatment visit 10 mg/m2
Reaction with plasma proteinsRenal excretion
Plasma Compartment
CDDP
Tumor Compartment
CDDP/epi gel
CDDP
Intratumoral Injection
Plasma Compartment
CDDP
Reaction with plasma proteinsRenal excretion
Tumor Compartment
CDDP
CDDP
Intravenous Injection
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Retention of Platinum in Murine RIF Tumors Following Administration of 195Pt-CDDP
4 h 24 h 72 h8 h5 min 1 h 48 h
Murine RIF-1 tumors, dermal, ~ 900 mm3
CDDP/epi gel (CDDP 4 mg/mL, epi 0.1 mg/mL) 50 µL intratumoral. CDDP suspension (CDDP 4 mg/mL)50 µL intratumoral CDDP solution (CDDP 1 mg/mL) 200 µL intravenous
195Pt 300 nCi/mouse
0 .0 33>3 0 0 .0 0 30 .3 < 0. 0 0 3
P t Co n ce n tra tio n (m M )
Murine SCCVII tumors
1 cm
Murine RIF-1 tumors, dermal, ~900 mm2
CDDP/epi gel (CDDP 4 mg/mL, epi 0.1 mg/mL) 50 μL i.tCDDP suspension (CDDP 4 mg/mL) 50 μL i.t.CDDP solution (CDDP 1 mg/mL) 200 μL i.t.195Pt 300 n Ci/mouse
CDDP Epi/Gel
CDDPSuspension
Intratumoral 195Pt-CDDP
>30
3
0.3
0.03
0.003
<0.003
Pt
Co
nce
ntr
atio
n (
mM
)
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Ability of Repeated Injection to Attain Good Drug Distribution
• Dose based on tumor volume: 0.25 mL gel/cm3 tumor, maximum dose 40 mg
• CDDP intratumoral distribution improves as tumor is destroyed
Week 1 Week 2 Week 3
Initial CDDP distribution
to viable tumor
BetterCDDP distribution
to viable tumor
Best CDDP distribution
to viable tumor
= viable tumor = dead tumor
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Challenge: Trial Design and Sequence of Events
• Original design– Primary endpoint: response rate of “Most Troublesome
Tumor” (MTT)– Collect information on clinical benefit:
• Improvement in symptoms• Prevention of catastrophic complications
• Pivotal trials powered on MTT response rate
• Increased emphasis on clinical benefit as an endpoint since trials started– FDA requested analysis of “Patient Benefit” as an additional
primary endpoint
• Problem – Many different kinds of symptoms– Impossible to accrue enough patients
• Integrated analysis required to increase power
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Challenge: Assessing Clinical Benefit
• Heterogeneity of symptoms– Many different kinds of symptoms– Variation in the number of symptoms per patient– Some symptoms are more important than others
• Palliation versus prevention– Both important
• Dichotomous yes/no answer on clinical benefit preferable– How to combine measures of palliation and prevention?
• How to deal with situation where most critical symptom gets better but others worsen?
• How to adjust palliation scores for differences in importance of the symptom to the patient?
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Clinical Reality
• Achieving any kind of improvement is very difficult– Recurrent/refractory
– Far advanced
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Approaches Taken to Assess Clinical Benefit
• Tumor shrinkage– Value often obvious to patient and physician– Fundamentally different from tumors at less critical sites– Shrinkage is reasonable direct measure of clinical benefit
• Palliation– Identified “Most Troublesome Tumor” and most important
symptom– 4 point scales– Tracked progress toward goals prospectively and
independently selected by patient and physician
• Prevention– Identified critical structures threatened– Measured success in avoiding anticipated complication
• Patient Benefit Algorithm developed to provide yes/no answer
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Clinical Study Results
Richard D. Leavitt, M.D.Senior Vice President, Medical Affairs
Matrix Pharmaceutical, Inc.
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Study Schema: Studies 414 and 514
CDDP/epi gel
Placebo gel
Evaluate
Follow-up monthly
Randomize 2:1
*At progression any time after 3 blinded treatments
Crossover to active drug*
Open-LabelDouble-Blind
Q 1 W x 6
• Identical study design• All ITT analyses • Simultaneous study unblinding
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Efficacy
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All Patients First Considered for Standard Therapy
•89% previously received multiple therapeutic modalities
•89% of MTTs in a previously radiated field
ISE T-006.1 for no. of MTTs in prev. irrad. field,
ISE E-4 for Venn diagram
44%44% Radiation & Radiation &
SurgerySurgery
39%39% Radiation, Radiation, Surgery, &Surgery, &
ChemotherapyChemotherapy
46%46% ChemotherapyChemotherapy(n = 82)(n = 82)
94%94% RadiationRadiation(n = 168)(n = 168)
87%87% SurgerySurgery
(n = 155)(n = 155)
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Objective Response Rate of Most Troublesome Tumor (MTT)
CDDP/epi gel Placebo gel p-value1
Study 414
CR + PR 34% (21/62) 0% (0/24) < 0.001
CR 23% (14/62) 0% (0/24)
PR 11% (7/62) 0% (0/24)
Study 514
CR + PR 25% (14/57) 3% (1/35) <0.007
CR 16% (9/57) 3% (1/35)
PR 9% (5/57) 0% (0/35)
Combined Results
CR + PR 29% (35/119) 2% (1/59) <0.001
CR 19% (23/119) 2% (1/59)
PR 10% (12/119) 0% (0/59)1Exact Cochran-Mantel-Haenszel
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All Partial Responses in Blinded Phase79% - 99%
79%
83%83%
87%
88%88%
95%
96%96%
98%
99%
99%
0 20 40 60 80 100
179721102688
549451105133
549625415372
177227531992
Pa
tie
nt
ID
Percent Reduction in Tumor Volume
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Prompt and Durable Objective Response
35 Responders* Days Range (days)
Time to response (median) 21 7 - 162
Duration of response (median) 78 30+ - 554+
*33 of 35 responders still responding at time of study exit or censoring
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Time to Tumor Progression
Time to Tumor Progression
CDDP/Epi Gel Placebo Gel
Median (days) 149 35
Range (days) 5 - 564+ 5 - 263+
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High Objective Response After Crossover from Placebo to CDDP/Epi Gel
Studies 414 & 514 Combined
Objective Response 27% (11/41)
CR 17% (7/41)
PR 10% (4/41)
Mean size increased from 5.7 to 10.8 cm3 from baseline to crossover
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High Objective Response in Patients with Prior Systemic Platinum Therapy
Yes No
29% (14/48) 30% (21/71)
Prior Cisplatin or Carboplatin
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Patient BenefitTreatment Goal Questionnaire
• The Instrument
• The Results
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Treatment Goals Questionnaire
• Assesses patient-specific benefit of local therapy
• Prospectively selected treatment goals– Primary goals
– Other selected goals – “secondary”
– Palliative goals• 4-point scale• Benefit required 28-day duration• Worsening scored after 7-day decline
– Preventive goals• Scored as met for ≥ 28 days or not met
• Independently validated by Center for Outcomes Research
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One-Point Difference Is Clinically MeaningfulPain Control
Level 4: Pain cannot be relieved by any medication
Level 3: Prescription medication required to relieve pain (e.g. narcotics, piroxicam)
Level 1: No medication required
Level 2: Over-the-counter medication relieves pain (e.g. aspirin, acetaminophen)
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Determination of Patient Benefit
• Patient Benefit Algorithm based solely on primary treatment goals prospectively selected by patient and investigator
YES = If either goal is met and neither worsens
NO = If neither goal is met or if either goal worsens
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Achievement of Patient Benefit
1Exact Cochran-Mantel-Haenszel
Study CDDP/Epi Gel Placebo p-value1
414 (n = 86) 34% (21/62) 17% (4/24) 0.18
514 (n = 92) 19% (11/57) 9% (3/35) 0.24
Combined(n = 178)
27% (32/119) 12% (7/59) 0.046
• Of the 41 patients randomized to placebo who crossed over to open label CDDP/epi gel, 11 (27%) achieved Patient Benefit
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Association of Tumor Response and Patient Benefit
Exact Cochran-Mantel-Haenszel
p = 0.006
Combined 414/514
Responder Non-responder
Benefitter 47% (17/36) 15% (22/142)
Non-benefitter 53% (19/36) 85% (120/142)
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Patients and Investigators Attained Prospectively Selected Palliative Goals
CDDP/Epi Gel Placebo GelOdds Ratio p-value1
Prospectively Selected Primary Palliative Goal
13% (13/99) 4% (2/51) 3.7 0.081
Any Prospectively Selected Palliative Goal
18% (20/111) 6% (3/54) 3.7 0.032
1Exact Cochran-Mantel-Haenszel
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Attainment of Palliative Goals or Unforeseen Benefits
CDDP/Epi Gel Placebo GelOdds Ratio
p-value1
Prospectively-Selected Primary Palliative Goal
13% (13/99) 4% (2/51) 3.7 0.081
Any Prospectively-Selected Palliative Goal
18% (20/111) 6% (3/54) 3.7 0.032
Any Palliative Goal or Unforeseen Benefit
34% (40/119) 8% (5/59) 5.5 < 0.001
1Exact Cochran-Mantel-Haenszel
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Association Between Tumor Response and Achievement of Palliative Goals or Unforeseen Benefits
RespondersNon-
Respondersp-value1
Prospectively-Selected Primary Palliative Goal
28% (8/29) 7% (5/70) 0.009
Any Prospectively-Selected Palliative Goal
33% (11/33) 12% (9/78) 0.007
Any Palliative Goal or Unforeseen Benefit
54% (19/35) 25% (21/84) 0.005
1Exact Cochran-Mantel-Haenszel
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Prevention of Major Complications Is Central to the Management of Patients with HNSCC
• Invasion of vital structures is devastating
• Airway obstruction directly threatens life
• Impaired swallowing compromises nutrition and quality of life
Success in achieving preventive goals can be clinically meaningful
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Structures Specified by Investigators as Threatened
Prevent Obstruction n = 26 goals Trachea, airway, etc. 13 Mouth/nose 4 Pharynx/oropharynx 3
Esophagus 2
Major vessels 2
Eye/vision 1 Not stated 1Prevent Invasion n = 50 goals Major vessels 31 Eye/vision 4 Skull/brain/vertebra 2 Trachea, airway, etc. 4 Mouth, nose 2
Pharynx/oropharynx 1
Not stated 6
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Attainment of Preventive Goals
CDDP/Epi Gel Placebo GelOdds Ratio
p-value1
Prospectively-Selected Primary Preventive Goal
62% (26/42) 26% (6/23)* 4.6 0.027
*Placebo patients often did not attain a preventive goal when disease progressed and patient was crossed over to CDDP/epi gel or left study
1Exact Cochran-Mantel-Haenszel
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Challenges in Evaluating Preventive Goals
• FDA correct: Direct comparison between the two arms has limitations
• Difficult to estimate rate of attainment of preventive goals on the placebo arm– Tumors rapidly progressing on placebo arm
(5.7 to 10.8 cm3)
– Not enough placebo patients on study for 28 days
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Inclusion of Preventive Goals in Assessment of Patient Benefit is Appropriate
• Reasonable to include rate of attainment of preventive goals– Single Patient Benefit outcome pre-specified palliative
and preventive goals
– Investigators believe prevention is crucial
– Algorithm is a valid measure of Patient Benefit
– Completing planned treatment is a valid indirect measure of clinical benefit
• Post-hoc examination of independent contribution of palliation to Patient Benefit should be secondary
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Supportive Efficacy Data
Open Label, Phase II Solid Tumor Studies
Study 403 67 patientsStudy 503 59 patients
Same efficacy endpoints
46
MTT Response in Open-Label Solid Tumor Studies 403 and 503
Study CDDP/Epi Gel95% Confidence
Interval
403 CR + PR 31% (20/65) 20 - 44%
CR 17% (11/65)
PR 14% (9/65)
503 CR + PR 41% (24/59) 28 - 54%
CR 14% (8/59)
PR 27% (16/59)
Combined CR + PR 35% (44/124) 27 - 45%
CR 15% (19/124)
PR 20% (25/124)
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Patient Benefit and Association of Objective Response of Most Troublesome Tumor
Patient Benefit Rate
Study 403 37% (24/65)
Study 503 25% (15/59)
Association of Benefit & Tumor Response
Responders Non-Responders
403 Benefitters (n = 24) 55% (11/20) 29% (13/45) p = 0.055
503 Benefitters (n = 15) 50% (12/24) 9% (3/35) p = <0.001
Chi-squared test
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Safety
• Dosing Accuracy
• Adverse Events
• Local Cytotoxic Effects
• Clinically Important Adverse Events
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Dosing Errors Were Rare in Studies 414 & 514
CDDP/Epi Gel (n = 533)*
Placebo (n = 186)
n (%) n (%)
No discrepancy 317 (59%) 117 (63%)
Tumor unable to accommodate 59 (11%) 28 (15%)
Tumor responded 33 (6%) 0 (0%)
Adverse event 22 (4%) 10 (5%)
Dose calculation error 20 (4%) 12 (6%)
Patient refused treatment or requested delay 8 (2%) 0 (0%)
Reflux 9 (2%) 4 (2%)
Other 65 (12%) 15 (8%)
*Includes 83 visits at which no dose was given
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All Adverse Events, Treatment-Related and Unrelated, Reported in ≥ 8% of Patients
Adverse Event CDDP/Epi Gel (n = 150) Placebo (n = 75)Mild/Moderate Severe Mild/Moderate Severe
Immediate injection effects
Pain 17% (26) 10% (15) 16% (12) 4% (3)Local reactions at treatment site
Pain 18% (27) 12% (18) 11% (8) 7% (5)Facial edema 6% (10) 3% (5) 0 0Infection 6% (10) 1% (2) 1% (1) 0
Systemic/other local effectsPain 15% (22) 7% (10) 11% (8) 4% (3)Asthenia 9% (14) 5% (8) 7% (5) 4% (3)Facial edema 7% (11) 5% (7) 1% (1) 1% (1)Infection 8% (12) 2% (3) 8% (6) 1% (1)Fever 9% (13) <1% (1) 7% (5) 0Headache 8% (12) <1% (1) 4% (3) 3% (2)Nausea 14% (21) 3% (4) 5% (4) 3% (2)Vomiting 14% (21) 2% (3) 1% (1) 1% (1)Constipation 11% (16) 3% (4) 4% (3) 0Anorexia 8% (12) 3% (4) 1% (1) 0Dysphagia 7% (11) 3% (4) 4% (3) 1% (1)Anemia 6% (10) 4% (6) 5% (4) 1% (1)Dehydration 3% (4) 6% (9) 4% (3) 0Dyspnea 5% (8) 5% (8) 5% (4) 3% (2)
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Many Patients Had Tumor-Related Tissue Conditions at Study Entry
Baseline
0 20 40 60 80 100
Erythema
Swelling
Bleeding
Erosion
Ulceration
Necrosis
Eschar
Severe
CDDP/epi gel
Placebo gel
Mild/Mod
% of Patients
52
Local Cytotoxic Effects (Randomized Phase)
Worsened from Baseline
0 20 40 60 80 100
Severe
CDDP/epi gel
Placebo gel
Mild/Mod
% of Patients
Erythema
Swelling
Bleeding
Erosion
Ulceration
Necrosis
Eschar
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Other Clinically Important Adverse Events
• Cerebrovascular events– 6 patients (5 CDDP/epi gel, 1 placebo)
– Most likely caused by carotid artery vasospasm
– No treatment-related events after study amendment
• Cardiovascular events – Nonfatal cardiopulmonary arrest in one patient
– Transient increases in blood pressure and pulse during drug administration
54
Summary of Clinical Efficacy and Safety of CDDP/Epi Gel
• Two adequate, placebo-controlled clinical trials in recurrent advanced HNSCC – confirmatory and complementary
• Effective local control of tumors in patients with recurrent HNSCC
• Patients achieved benefit, palliation of symptoms, and prevention of complications
• Patient Benefit associated with tumor response
• Supportive trials with high response rate and Patient Benefit in other solid tumors
• Side effects manageable with limited systemic effects
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Discussion of Clinical Benefit Issues
Stephen B. Howell, M.D. Professor of Medicine
Director, Cancer Pharmacology University of California San Diego
Cancer Center
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Rates of Attainment of Primary Goals in Patients Randomized to CDDP/Epi Gel or Placebo Gel, Studies Combined
Selected by Patient Selected by Physician
CDDP/Epi Gel
Placebo Gel
CDDP/Epi Gel
Placebo Gel
Wound care 12% (3/26) 0% (0/9) 13% (3/23) 0% (0/13)
Pain control 11% (4/38) 5% (1/22) 12% (3/26) 0% (0/14)
Obstructive symptom 11% (3/27) 0% (0/11) 8% (2/24) 0% (0/5)
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FDA Analysis of Palliative Goals
• To score “better” required 28 days; “worse” required 7 days – Conservative scoring– Expect more patients to worsen than improve– CDDP/epi gel expected to produce transient worsening in
some patients
• Patients stayed on CDDP/epi gel arm longer than on placebo (median 41 vs 28 days), and therefore had a greater chance of worsening
Study CDDP/Epi Gel Placebo Gel
414 Better 6% (3/51) 5% (1/20)
Worse 25% (13/51) 10% (2/20)
514 Better 19% (10/54) 3% (1/33)
Worse 22% (12/54) 12% (4/33)
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Analysis of Palliative Goals Over First 28 Days Adjusted for Equal Scoring Intervals
Study CDDP/Epi Gel Placebo Gel414 Better 18% (9/51) 10% (2/20)
Worse 20% (10/51) 10% (2/20)
514 Better 11% (6/53) 3% (1/33)Worse 13% (7/53) 6% (2/33)
Combined Better 14% (15/104) 6% (3/53)Worse 16% (17/104) 8% (4/53)
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All Palliative Goals: Rate of Worsening on Any Scale During Treatment and 1st Month of Follow-up
Patient Goal
47% (7/15)24% (11/45) Obstructive symptom
21% (6/28)22% (11/51) Pain control
24% (4/17)27% (10/37) Wound care
Physician Goal
43% (20/46)43% (46/107)Total
13% (2/16)28% (11/40) Wound care
11% (2/18)18% (7/39) Pain control
75% (6/8)27% (9/33)Obstructive symptom
Placebo Gel (n = 46)
CDDP/Epi Gel (n = 107)Goal
“Worsening” defined as worsening of at least one scale point from baseline for at least 2 consecutive visits. Assessments for patients randomized to placebo gel obtained after start of open-label CDDP/epi gel are not excluded.
60
Attainment of Prospectively Selected Primary Palliative Goals – Within Patient Analysis
Attained Patient’s and/or Physician’s Primary Palliative Goal*
Attained Primary Palliative Goal But Other Person’s Assessment of Primary Goal Worsened
4% (2/53)
Placebo Gel
0% (0/53)
4% (2/53)
12% (13/104)
CDDP/Epi Gel
0% (0/104)
12% (13/104)Net Primary Palliative Goal
*Denominator does not exclude unattainable goals
61
Attainment of Any Prospectively Selected Palliative Goal – Within Patient Analysis
Attained Any Primary or Secondary Palliative Goal
Attained Any Primary or Secondary Palliative Goal But Another Palliative Goal Worsened
6% (3/54)
Placebo Gel
2% (1/54)
4% (2/54)
18% (20/111)
CDDP/Epi Gel
4% (4/111)
14% (16/111)Net Palliative Goal Attainment
62
Pivotal Trials Provide Substantial Evidence of Clinical Benefit
• Significant difference in MTT response rate in both studies – obvious clinical benefit
• Positive trend for Patient Benefit in both studies; statistical significance in the prospective integrated analysis
• Palliation– Improvement for each type of symptom when examined
individually– Integrated analysis of all primary and secondary palliative
goals significant (p = 0.032)– Analysis of primary and secondary goals and unforeseen
benefits significant in each study individually (414: p = 0.036; 514: p = 0.007)
• Studies 403 and 503 = supportive data– High response rate (35%)– High Patient Benefit rate (31%)
63
Summary of Risks and Benefits
Glenn Mills, M.D.Professor of Medicine
Director of Clinical Research and Head of Aerodigestive Malignancy Program
Principal Investigator SWOG Feist-Weiller Cancer Center, LSUHSC-Shreveport
64
Risks/Benefits of Current Treatment Options for Recurrent Local Disease
• No Therapy – Local – bleeding, airway, pain, nutrition and appearance
– Decline in quality of life
– May shorten patient’s life
• Risks of current treatments– Radiation therapy – ineffective dose if in-field relapse
– Surgery – usually not an option
– Chemotherapy – excessive toxicity*
• Marginal improvement in survival
*Forastiere, A.A., et al., JCO 19:1088-95, 2001
65
Risks and Benefits of CDDP/Epi Gel
• Risks– Side effects – local, manageable
– Systemic effects – uncommon, usually not severe, patient selection
• Benefits– High complete response rate
– Clinical benefit – both palliative and preventive goals
– Prompt responses – short duration of treatment
– Outpatient administration
66
Patient 414-1795
Day 51Day 1
67
Patient 514-2736
Day 1 Day 210
Tumor Uvula
Uvula
Tongue
Tongue
68
Need for CDDP/Epi Gel in the Treatment of Recurrent Local-Regional HNSCC
• Third form of local therapy
• Needed addition to local treatment options
• Effective/beneficial therapy for local disease
69
Oncologic Drugs Oncologic Drugs Advisory Committee MeetingAdvisory Committee Meeting
NDA 21-236NDA 21-236
Cisplatin/Epinephrine Injectable Gel for Cisplatin/Epinephrine Injectable Gel for the Treatment of Squamous Cell the Treatment of Squamous Cell
Carcinoma of the Head and NeckCarcinoma of the Head and Neck
Matrix Pharmaceutical, Inc.