CRC-1

The Need for 3rd-Line Therapy in Non-Small Cell Lung Cancer

The Need for 3rd-Line Therapy in Non-Small Cell Lung Cancer

Frances A. Shepherd, MD

Scott Taylor Chair in Lung Cancer ResearchPrincess Margaret Hospital

Professor of Medicine, University of Toronto

Frances A. Shepherd, MD

Scott Taylor Chair in Lung Cancer ResearchPrincess Margaret Hospital

Professor of Medicine, University of Toronto

CRC-2

> 110,000 patientspotential candidates forsystemic therapy yearly

> 110,000 patientspotential candidates forsystemic therapy yearly

MetastaticMetastaticResectableResectablediseasedisease

LocallyLocallyadvancedadvanced

Most Patients With NSCLC Will Require Systemic Therapy

Most Patients With NSCLC Will Require Systemic Therapy

~80% relapse~80% relapse

Shepherd. Shepherd. Semin OncolSemin Oncol. 1999.. 1999.

~50% relapse~50% relapse

CRC-3

Systemic Treatment for Advanced NSCLCChemotherapy — 1st-Line

Systemic Treatment for Advanced NSCLCChemotherapy — 1st-Line

Modestly improves survival and symptoms

Platinum-based regimens the standard

Uncertain benefit in patients with PS 2

Toxicity an issue 1st- and 2nd-line

Modestly improves survival and symptoms

Platinum-based regimens the standard

Uncertain benefit in patients with PS 2

Toxicity an issue 1st- and 2nd-line

CRC-4

2nd-Line Treatment for NSCLC2nd-Line Treatment for NSCLC

Docetaxel is the only chemotherapy approved for NSCLC

Response rate is low –— only 6% to 7%

Demonstrated benefit in terms of survival and symptom control

Toxicity is an issue

Docetaxel is the only chemotherapy approved for NSCLC

Response rate is low –— only 6% to 7%

Demonstrated benefit in terms of survival and symptom control

Toxicity is an issue

CRC-5

3rd-Line Treatment for Advanced NSCLC3rd-Line Treatment for Advanced NSCLC

For NSCLC, no standard definition for disease refractory to both platinum and docetaxel

Clinical definition of 3rd-line: patients previously treated with a platinum and docetaxel who are not expected to benefit from additional treatment with same

Single-agent chemotherapy now used for 3rd-line

For NSCLC, no standard definition for disease refractory to both platinum and docetaxel

Clinical definition of 3rd-line: patients previously treated with a platinum and docetaxel who are not expected to benefit from additional treatment with same

Single-agent chemotherapy now used for 3rd-line

CRC-6

Massarelli et al. ASCO. 2002.

Outcomes in NSCLC Patients From Startof 3rd- and 4th-Line Therapy

Outcomes in NSCLC Patients From Startof 3rd- and 4th-Line Therapy

Months after start of 3rd- or 4th-line therapy

Su

rviv

al p

rob

abil

ity

0 6 12 18 240.0

0.2

0.4

0.6

0.8

1.0

0.1

0.3

0.5

0.7

0.9 Objective response 2.3% (n = 1)

Median survival 4.5 months

1-year survival 5%

N = 43

CRC-7

NSCLC Commonly Causes Disease-Related SymptomsNSCLC Commonly Causes Disease-Related Symptoms

Specific symptoms– Shortness of breath– Cough– Tightness in the chest– Difficulty breathing– Poor Appetite and Weight loss– Fatigue

Type, severity, frequency depend on tumor location, disease burden, and growth rate

Specific symptoms– Shortness of breath– Cough– Tightness in the chest– Difficulty breathing– Poor Appetite and Weight loss– Fatigue

Type, severity, frequency depend on tumor location, disease burden, and growth rate

CRC-8 Significance of Objective Responses in

3rd-Line Therapy of NSCLC

Significance of Objective Responses in

3rd-Line Therapy of NSCLC

Measure of antitumor activity

Associated with symptom improvement

Associated with better patient outcomes

Measure of antitumor activity

Associated with symptom improvement

Associated with better patient outcomes

CRC-9

Disease-Related Symptoms in NSCLCDisease-Related Symptoms in NSCLC

When asked, 68% of patients with NSCLC who had already received platinum, stated they would choose chemotherapy compared to best supportive care if symptoms could be substantially reduced, even if survival was not prolonged

When asked, 68% of patients with NSCLC who had already received platinum, stated they would choose chemotherapy compared to best supportive care if symptoms could be substantially reduced, even if survival was not prolonged

Silvestri et al. 1998

CRC-10

Goals of 3rd-Line Therapy in NSCLCGoals of 3rd-Line Therapy in NSCLC

Improve disease-related symptoms

Improve performance status

Treatment not an additional burden

– Enhanced patient control

– Holiday from IV therapy

– Less time away from home for treatment

Improve disease-related symptoms

Improve performance status

Treatment not an additional burden

– Enhanced patient control

– Holiday from IV therapy

– Less time away from home for treatment

CRC-11

3rd-Line Therapy forNon-Small Cell Lung Cancer: an Unmet Need

3rd-Line Therapy forNon-Small Cell Lung Cancer: an Unmet Need

Increasing numbers of patients with NSCLC for 3rd-line therapy

Most of these patients have significant disease-related symptoms

No approved 3rd-line agents

Standard chemotherapies a poor solution

3rd-line therapy for NSCLC represents an unmet medical need

Increasing numbers of patients with NSCLC for 3rd-line therapy

Most of these patients have significant disease-related symptoms

No approved 3rd-line agents

Standard chemotherapies a poor solution

3rd-line therapy for NSCLC represents an unmet medical need