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Table of Contents

Oncologic Drugs Advisory Committee Meeting



Independent Experts

Current Management of Recurrent Head and Neck Cancer

Scope of the Problem

Standard Therapy

Locally Recurrent HNSCC

Unmet Needs in Local Recurrence

Locally Recurrent Head and Neck Cancer

Pharmacologic Rationale and Challenges Associated with Demonstration of Clinical Benefit

Indication Refined Since NDA Filing

Product Description

Pharmacologic Rationale for Intratumoral Treatment

Retention of Platinum in Murine RIF Tumors Following Administration of 195Pt-CDDP

Ability of Repeated Injection to Attain Good Drug Distribution

Challenge: Trial Design and Sequence of Events

Challenge: Assessing Clinical Benefit

Clinical Reality

Approaches Taken to Assess Clinical Benefit

Clinical Study Results

Study Schema: Studies 414 and 514


All Patients First Considered for Standard Therapy

Objective Response Rate of Most Troublesome Tumor (MTT)

All Partial Responses in Blinded Phase 79% - 99%

Prompt and Durable Objective Response

Time to Tumor Progression

High Objective Response After Crossover from Placebo to CDDP/Epi Gel

High Objective Response in Patients with Prior Systemic Platinum Therapy

Patient Benefit Treatment Goal Questionnaire

Treatment Goals Questionnaire

One-Point Difference Is Clinically Meaningful Pain Control

Determination of Patient Benefit

Achievement of Patient Benefit

Association of Tumor Response and Patient Benefit

Patients and Investigators Attained Prospectively Selected Palliative Goals

Attainment of Palliative Goals or Unforeseen Benefits

Association Between Tumor Response and Achievement of Palliative Goals or Unforeseen Benefits

Prevention of Major Complications Is Central to the Management of Patients with HNSCC

Structures Specified by Investigators as Threatened

Attainment of Preventive Goals

Challenges in Evaluating Preventive Goals

Inclusion of Preventive Goals in Assessment of Patient Benefit is Appropriate

Supportive Efficacy Data

MTT Response in Open-Label Solid Tumor Studies 403 and 503

Patient Benefit and Association of Objective Response of Most Troublesome Tumor


Dosing Errors Were Rare in Studies 414 & 514

All Adverse Events, Treatment-Related and Unrelated, Reported in = 8% of Patients

Many Patients Had Tumor-Related Tissue Conditions at Study Entry ? Baseline

Local Cytotoxic Effects (Randomized Phase) ? Worsened from Baseline

Other Clinically Important Adverse Events

Summary of Clinical Efficacy and Safety of CDDP/Epi Gel

Discussion of Clinical Benefit Issues

Rates of Attainment of Primary Goals in Patients Randomized to CDDP/Epi Gel or Placebo Gel, Studies Combined

FDA Analysis of Palliative Goals

Analysis of Palliative Goals Over First 28 Days Adjusted for Equal Scoring Intervals

All Palliative Goals: Rate of Worsening on Any Scale During Treatment and 1st Month of Follow-up

Attainment of Prospectively Selected Primary Palliative Goals Within Patient Analysis

Attainment of Any Prospectively Selected Palliative Goal Within Patient Analysis

Pivotal Trials Provide Substantial Evidence of Clinical Benefit

Summary of Risks and Benefits

Risks/Benefits of Current Treatment Options for Recurrent Local Disease

Risks and Benefits of CDDP/Epi Gel

Patient 414-1795

Patient 514-2736

Need for CDDP/Epi Gel in the Treatment of Recurrent Local-Regional HNSCC

Oncologic Drugs Advisory Committee Meeting

Author: Matrix