S

European Studies in

Lung Cancer

Paul Baas

13th International Lung Cancer Conference

2012, Huntington Beach, CA

Overview of trials and other

European research activities

Question

Which country: which flag?

Studies in NSCLC: Europe 2012

EORTC 22055-08053:

Trial Design LUNG-ART

Accrual: 4 years

Follow-up: 1 year

Completely

resected

NSCLC with

proven

N2

involvement

Post-op

CT

R

A

N

D

O

M

No

Irradiation

Thoracic

irradiation

54 Gy/30 fr

DFS

Local control

OS

2nd cancer

Late Toxicity

Max 6 wks

Max

2 wks

Max 2 wks

2011: ± 120 patients entered

EXPERIMENTAL T2-T3 RAP80

(T1-T2 BRCA1)

T2-T3 RAP80

(T3 BRCA1)

Gem/Cis

Docetaxel

Docetaxel/Cis

T1 RAP80

(T1-T3 BRCA1)

International BREC

(BRCA1 Expression Customization)

CONTROL Docetaxel/Cis

Advanced NSCLC 1:1

216 patients per arm – total: 432

Spanish Lung Cancer Group, French Lung Cancer Group, Hellenic Cooperative Cancer Group

Gulf countries, Saudi Arabia, Colombia, China

CONVERT

UK/French/EORTC 08072

S Recently opened

S Intergroup study

S SCLC LS cisplatin/etoposide with 45 Gy BID or 60 Gy OD

S Accrual through EORTC (6 sites open)

S Survival benefit OD RT: 12% at 2 years

(CI 43-50%) 532 patients

Concurrent ONce-daily VErsus twice-daily RadioTherapy in LS SCLC

CONVERT STUDY

(SCLC LS) EORTC 08072-22074

Histo-/cytologically

confirmed LD

SCLC

ECOG PS 0-2

R

A

N

D

O

M

Once-daily arm

(OD)

RT 66Gy/45D/33F

Twice-daily arm

(BD)

RT 45Gy/19D/30F

Max 2 wks

Chemotherapy: 4 to 6 Cycles , every 3 weeks.

- Cisplatin 25 mg/m2 iv D1-3 or 75 mg/m2 iv D1

- Etoposide 100 mg/m2 iv D1-3

RT starting on day 22 of cycle1

SD

PR

CR

PCI

<SD

No

PCI

Primary end-point

• Overall survival

Secondary end points

• Local progression-free survival

• Metastasis-free survival

• CTCAE v3.0 toxicity

• Chemotherapy dose intensity

• Radiotherapy dose intensity

Number of patients: 362/532 patients entered

CONVERT STUDY

(SCLC LS) EORTC 08072-22074

EORTC 08092

S Double blind randomized phase III study of maintenance

pazopanib versus placebo in NSCLC patients non

progressive after first line chemotherapy.

S Integrated phase II/III study

S Pazopanib or placebo starts at 600 mg/day then at a daily

dose of 800 mg if well tolerated.

S Stats: improvement in OS from 9.7 to 12.7 months

required number of patients: 587

Study design EORTC 08092

Pazopanib maintenance in NSCLC

Placebo

Pazopanib 800 mg daily

Maintenance

4 cycles

Chemotherapy

CR/PR/

SD

Stage IIIB/IV NSCLC

No prev. TKI

R

IA for Futility

PFS

Pazopanib 800 mg daily

Maintenance

Placebo

Final Analysis

OS

N=587

S Primary endpoint:

overall survival (OS)

S Secondary endpoints:

PFS, toxicity, CRP, QoL,

compliance,

health economics

S Interim analysis for futility

at +/- 154 PFS events

Endpoints EORTC 08092

European Thoracic Oncology Platform

Goal

S To serve as an umbrella for the national tumor

groups

S To facilitate large studies in Europe

S To add translational dedicated research

S To identify centers suitable for certain studies

S Not to become a second EORTC

About LUNGSCAPE

S The LUNGSCAPE addresses the challenges of studying the molecular

epidemiology of lung cancer

S by coordinating and harmonizing the procedures of of lung cancer

specialists working in translational research across Europe

S by facilitating analysis of larger series of cases.

S This will:

S Expedite knowledge of the prevalence and context of current and

emerging molecular biomarkers

S Facilitate more rapid translation of biomarker knowledge to the clinic

S Provide a platform for marker-driven trials of novel therapeutics

Comprehensive clinical data

capture

ETOP, 2012

Stepwise evolution

Step 1:

Retrospective analysis of about 2400 completely resected NSCLC

from a limited number of sites:

IHC, FISH and mutation testing on FFPE tumor tissue

Step 2:

Prospective studies including biopsies and advanced disease and

increasing to the number of participating sites

Further steps under considerations:

Molecular signatures and next generation sequencing on selected

matched frozen tissue, circulating biomarkers, technology

platforms, resource utilization and health economics

ETOP, 2012

Histology of accepted cases

(June 20, 2012; N = 1863)

ETOP, 2012

Stage of accepted cases (June 20, 2012; N = 1863)

ETOP, 2012

ETOP 2-11 BELIEF An open-label phase II trial of erlotinib and bevacizumab in

patients with advanced non-small cell lung cancer and

activating EGFR mutations

Sample size: 102 patients

ETOP, 2012

ETOP 2-11 BELIEF –

Key Eligibility Criteria

Inclusion Criteria:

• Non-squamous histology

• EGFR ex19 or ex21 mutation

• Central confirmation

required

• Advanced TNM stage

• Stable brain metastases

allowed

• Measurable disease by

RECIST

• ECOG PS 0-2

• Age ≥ 18 years

• Signed informed consent

Exclusion Criteria:

• Previous systemic therapy for

metastatic disease, including

EGFR or VEGF inhibitors

• Significant hemoptysis

• Uncontrolled hypertension

• Relevant ischemia or

thromboembolism

• Full anticoagulation

• Recent major surgery or trauma

ETOP, 2012

ETOP 3-12 EMPHASIS-lung A randomized phase III trial of erlotinib versus docetaxel in

patients with advanced squamous cell NSCLC in 2nd line

chemotherapy stratified by VeriStrat Good vs VeriStrat Poor

Sample size: 500 patients

ETOP, 2012

ETOP 3-12 EMPHASIS-lung

Key Eligibility Criteria

Inclusion Criteria:

• locally advanced stage IIIB or

metastatic stage IV NSCLC of

squamous subtype

• Progressive disease,

measurable or evaluable

according to RECIST v1.1

• ECOG PS 0-2

• Age ≥ 18 years

• Adequate haematopoietic,

hepatic and renal function

Exclusion Criteria:

• Previous treatment with any

EGFR-TKI or docetaxel.

• Documented brain metastases

• Documented presence of

activating EGFR mutations

• Previous malignancy within the

past 5 years

ETOP, 2012

ETOP 4-13 STIMILI (ipilimumab)

A randomized phase II trial of consolidation ipilimumab vs placebo

in limited-stage SCLC after chemoradiotherapy

ETOP, 2012

ETOP 4-13 STIMULI

Key Eligibility Criteria

Inclusion Criteria:

• Limited stage disease (I-IIIB) SCLC

• Mean Lung dose ≤ 20 Gy or V20 ≤

35 %

• Pulmonary function

FEV1 > 40% predicted value &

DLCO > 40% predicted value

• Adequate haematopoietic, hepatic

and renal function

• PS 0-1

• Age > 18 years

Exclusion Criteria:

• Mixed small-cell and non-small-cell

histologic features

• Malignant pleural or pericardial

effusions

• Documented history of severe

autoimmune or immune mediated

symptomatic disease

• Interstitial pneumonia or pulmonary

fibrosis

• HIV, Hepatitis B or Hepatitis C

infection

• Previous radiotherapy to the thorax

ETOP, 2012

Thanks for your

attention