copyright © 2011 research to practice. all rights reserved. faculty meet the professors oncologist...

Copyright © 2011 Research To Practice. All rights reserved.

Faculty

Meet The Professors

Oncologist and Nurse Investigators Consult on Challenging Patient Cases

in Non-Small Cell Lung Cancer

Saturday, November 13, 20106:30 AM – 8:00 AM

Peabody Orlando Hotel

ModeratorNeil Love, MD

Mark A Socinski, MDMichelle M Turner, MS, CRNP

Beth Eaby-Sandy, MSN, CRNP, OCNRogerio C Lilenbaum, MD


Agenda

Module 1 Biomarker- and Histology-Guided Treatment of NSCLC: Ms Eaby-Sandy

Module 2 Current Options for Adjuvant Systemic Treatment of NSCLC: Ms Turner

Module 3 The Use of EGFR Tyrosine Kinase Inhibitors in NSCLC and Relevance of EGFR Tumor Mutations: Ms Eaby-Sandy

Module 4 Chemobiologic Management of Advanced NSCLC: Ms Turner

Panel Discussion and Response to Audience Questions


Temel JS et al. N Engl J Med 2010;363(8):733-42.


Case 1 (Ms Eaby-Sandy)

A 71-year-old woman and never smoker with EGFR wild-type metastatic NSCLC receives six cycles of pemetrexed/carboplatin/bevacizumab followed by maintenance pemetrexed/bevacizumab but then experiences disease progression. Assay of the tumor is positive for the EML4-ALK mutation, and she is currently participating in a clinical trial of crizotinib.


KRAS

Unknown

EGFRHER2

BRAFALK fusion

PIK3CAMEK1

ROS fusionPDGFR amp

Adeno

Squam

Large

Small

Courtesy of William Pao, AAAS-FDLI Colloquium on Personalized Medicine, 2009.

Lung Cancer Histologic and Molecular Subsets


Sandler A et al. N Engl J Med 2006;355:2542-50.Reck M et al. J Clin Oncol 2009;27(8):1227-34.Crinò L et al. Lancet Oncol 2010;11:733-40.


Faculty

Meet The Professors

Oncologist and Nurse Investigators Consult on Challenging Patient Cases

in Non-Small Cell Lung Cancer

Saturday, November 13, 20106:30 AM – 8:00 AM

Peabody Orlando Hotel

ModeratorNeil Love, MD

Mark A Socinski, MDMichelle M Turner, MS, CRNP

Beth Eaby-Sandy, MSN, CRNP, OCNRogerio C Lilenbaum, MD


Patel JD et al. J Clin Oncol 2009;27(20):3284-9.

Copyright © 2011 Research To Practice. All rights reserved.Patel JD et al. J Clin Oncol 2009;27(20):3284-9.

Efficacy Endpoints

Median progression-free survival 7.8 mos

Median overall survival 14.1 mos

Objective response rate 55%

Select Adverse Events Grade 3 Grade 4

Diverticulitis1 6% 2%

Thrombocytopenia 0% 8%

Neutropenia 4% 0%

Venous thrombosis 4% 2%1 One case of Grade IV diverticulitis with bowel perforation

Pem/Carbo/Bev with Maintenance Pem/Bev as First-Line Therapy for Nonsquamous NSCLC (N = 49)


POINTBREAK Phase III Trial Pemetrexed (Pem)/Carboplatin (C)/Bevacizumab (Bev) Maintenance Pem/Bev versus Paclitaxel/C/Bev Maintenance Bev in Patients with NSCLC

www.ClinicalTrials.gov, November 2010.

Eligibility

• Stage IIIB or IV nonsquamous NSCLC

RPemetrexed + Carboplatin +

Bevacizumab

Target accrual = 900

Paclitaxel + Carboplatin + Bevacizumab

MaintenancePemetrexed + Bevacizumab

MaintenanceBevacizumab


Pirker R et al. Lancet 2009;373(9674):1525-31.

Copyright © 2011 Research To Practice. All rights reserved.Pirker R et al. Lancet 2009;373(9674):1525-31.

Efficacy Parameter

Cetux + CV

(n=557)

CV

(n=568)Hazard Ratio p-value

Median overall survival

All patients

Nonsquamous

Squamous

11.3 mos

12.0 mos

10.2 mos

10.1 mos

10.3 mos

8.9 mos

0.87

0.94

0.80

0.044

Median progression-free survival 4.8 mos 4.8 mos 0.94 0.39

Overall response rate 36% 29% — 0.010

FLEX: Efficacy OutcomesEGFR expression-positive by IHC (>1 positive tumor cell)


Kwak EL et al. N Engl J Med 2010;363(18):1693-703.


Crizotinib Inhibition of the ALK Signaling Pathway

Bang Y et al. Proc ASCO 2010;Abstract 3.

ALK

Tumor cellproliferation

Cell survival

PI3K

BAD

AKT

STAT3/5

mTOR

S6K

RAS

MEK

ErKErK

PLC-Y

PIP2

IP3

Crizotinib


Best Response to Crizotinib in Patients with ALK-Positive Advanced NSCLC

Kwak EL et al. N Engl J Med 2010;363(18):1693-703. © 2010. Massachusetts Medical Society. All rights reserved.

60

40

0

20

10 20 70 7960504030

60

40

0

20

10 20 70 7960504030

Patient No.

Per

cen

t C

han

ge

fro

m B

ase

lin

e Disease progressionDisease progression Stable diseaseStable disease Partial responsePartial response Complete responseComplete response

-30%-30%


Grade 3/4 Adverse Events

Adverse Event (AE) Grade 3 Grade 4

ALT elevation 5% 1%

AST elevation 6% 0%

Lymphopenia 2% 0%

Hypophosphatemia 1% 0%

Neutropenia 1% 0%

Hypoxia 1% 0%

Pneumonitis 1% 0%

Pulmonary emoblism 1% 0%

Kwak EL et al. N Engl J Med 2010;363(18):1693-703.


Case 2 (Ms Turner)

A 61-year-old man with Stage II NSCLC received adjuvant docetaxel/cisplatin and bevacizumab on the ECOG-E1505 clinical trial and completed one year of maintenance bevacizumab in early 2010. The patient is now found on imaging to have a solitary metastasis in the adrenal gland.


Chemotherapy

Adjuvant chemotherapy (vinorelbine + cisplatin OR docetaxel + cisplatin OR gemcitabine + cisplatin OR pemetrexed + cisplatin)

Chemotherapy + bevacizumab

Adjuvant chemotherapy (as described above) with bevacizumab on d1 q3wk x 1y

Eligibility (Target accrual = 1,500)• Resection within the past six to 12 weeks

• ECOG PS 0-1• No history of CVA or TIA

• History of myocardial infarction or anginaacceptable if no evidence of active diseasewithin the past 12 months

* Patients are stratified according to type of chemotherapy, stage, histology and gender.

ECOG-E1505: A Phase II Study of Adjuvant Chemotherapy with or without Bevacizumab for Stage IB-IIIA NSCLC

R*



Bria E et al. Lung Cancer 2009;63(1):50-7.


Magnitude of Benefit of Adjuvant Chemotherapy for NSCLC: A Meta-analysis of Randomized Clinical Trials • Meta-analysis of 12 Phase III trials (from 1994-2007), and an

individual patient meta-analysis were conducted to determine if cisplatin-based chemotherapy improves survival over surgery (seven subpopulations examined, n = 7,334).

• Absolute benefit and the number of patients treated for one patient to benefit (NNT) were evaluated for magnitude of benefit.

Bria E et al. Lung Cancer 2009;63(1):50-7.

Results from Pooled Data

Adjuvant Chemotherapy vs. Surgery Only Relative Benefit Absolute Benefit NNT

Overall survival (n = 7,334) 7%-12% 2.5%-4.1% 24-39

Disease-free survival (n = 6,396) 11%-12% 4.2%-4.6% 22-24


What patient education information do you consider essential in a patient with non-small cell lung cancer about to begin treatment with….

Adjuvant cisplatin/paclitaxel


Surgical Treatment of Oligometastatic NSCLC: Analysis of Retrospective Cases Series

Site of Metastasis 5-Year Survival

Satellite nodules 28%

Ipsilateral nodules 21%

Brain metastasis 11% - 30%

Adrenal metastasis 26%

Pfannschmidt J, Dienemann H. Lung Cancer 2010;69(3):251-8.



A 71-year-old man with EGFR-mutated metastatic NSCLC and limited family support begins front-line therapy with erlotinib 150 mg daily. Significant side effects require dose reduction to 100 mg, which he is now tolerating well.


Epidermal Growth Factor Receptor (EGFR) Mutations


EGFR Signaling

Adapted by permission from Macmillan Publishers Ltd. (Arteaga CL. HER3 and mutant EGFR meet MET. Nat Med 13:675-7), copyright 2007.

Copyright © 2011 Research To Practice. All rights reserved.Adapted by permission from Macmillan Publishers Ltd. (Arteaga CL. HER3 and mutant EGFR meet MET. Nat Med 13:675-7), copyright 2007.

EGFR-TKI Mechanism of Action

Copyright © 2011 Research To Practice. All rights reserved.Adapted by permission from Macmillan Publishers Ltd. (Arteaga CL. HER3 and mutant EGFR meet MET. Nat Med 13:675-7), copyright 2007.

Resistance Mechanisms


Mok TS et al. N Engl J Med 2009;361(10):947-57.


Efficacy of Gefitinib vs C/P in East Asian Patients with NSCLC

Objective Response Rate (ORR) Gefitinib C/P P-value

Intent-to-treat population (n = 609; 608)

43.0% 32.2% <0.001

EGFR mutation-positive (n = 132; 129) 71.2% 47.3% <0.001

EGFR mutation-negative (n = 91; 85) 1.1% 23.5% 0.001

Progression-Free Survival (PFS) Hazard Ratio P-value

Intent-to-treat population 0.74 <0.001

EGFR mutation-positive 0.48 <0.001

EGFR mutation-negative 2.85 <0.001

Mok TS et al. N Engl J Med 2009;361(10):947-57.

Copyright © 2011 Research To Practice. All rights reserved.www.ClinicalTrials.gov, November 2010.Wakelee H et al. Oncologist 2007;12(3):331-7.

RADIANT Trial: A Phase III Study of Erlotinib or Placebo with or without Adjuvant Chemotherapy for Patients with Resected, EGFR-Positive NSCLC

Eligibility

• Resected Stage IB to IIIA• EGFR-positive by FISH or IHC4 cycles of platinum-based

chemotheraphy (optional)

Erlotinib 150 mg daily x 2 years

Observation

Protocol IDs: OSI-774-302, NCT00373425

Target accrual: 945 (Open)

* Stratified by histology (squamous versus other), gender, age, EGFR status, smoking status and adjuvant chemotherapy

2:1R*


Skin Rash from Tyrosine Kinase Inhibitors

Ricciardi S et al. Clin Lung Cancer 2009;10(1):28-35.

• Most frequent dermatologic side effect reported is acneiform eruption.• Affects mainly face, upper chest and/or back• Also known as acne, acneiform skin reaction/rash, follicular rash and maculopapular skin rash.


Incidence of Acneiform Eruption During Therapy with Epidermal Growth Factor Receptor Inhibitors

Ricciardi S et al. Clin Lung Cancer 2009;10(1):28-35.

EGFR Inhibitor Incidence of Acneiform Eruption

Erlotinib 79% (10.4% >Grade 3)

Cetuximab 80% (18% >Grade 3)

Gefitinib 53% (1.6% >Grade 3)

Panitumumab 70%-100% (<10% severe)

Matuzumab 64% (0% >Grade 3)


Case 4 (Ms Turner)

A 71-year-old man underwent concurrent docetaxel/carboplatin and radiation therapy in 2003 for localized NSCLC with positive margins. A biopsy of new pulmonary nodules in 2008 showed poorly differentiated adenocarcinoma. Paclitaxel/carboplatin/bevacizumab was administered but had to be discontinued because of toxicity issues.


What patient education information do you consider essential in a patient with non-small cell lung cancer about to begin treatment with….

carboplatin/pemetrexed/bevacizumab


Case 4 (Ms Turner)

A 71-year-old man underwent concurrent docetaxel/carboplatin and radiation therapy in 2003 for localized NSCLC with positive margins. A biopsy of new pulmonary nodules in 2008 showed poorly differentiated adenocarcinoma. Paclitaxel/carboplatin/bevacizumab was administered but had to be discontinued because of toxicity issues.


Eligibility

Unresectable nonsquamousStage III NSCLC

Standard-dose radiotherapy+ chemo consolidation chemo


RTOG-0617: A Phase III Trial of High-Dose (74 Gy) or Standard-Dose (60 Gy) Radiation Therapy Plus Chemotherapy

High-dose radiotherapy+ chemo consolidation chemo

Standard-dose radiotherapy + chemo and cetuximab consolidation chemo and cetuximab

High-dose radiotherapy + chemo and cetuximab consolidation chemo and cetuximab

R


Randomized, Double-Blind, Placebo-Controlled Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in NSCLC

Apricoxib 100 mg PO qd + docetaxel or pemetrexed q3 wks

Placebo PO qd + docetaxel or pemetrexed q3 wks

Protocol IDs: UMGCC 0822 (Open) Target Accrual: 130

Eligibility: Stage IIIb (pleural effusion) or IV NSCLC; progression after 1 prior platinum-based chemo; received prior erlotinib

R


copyright © 2011 research to practice. all rights reserved. faculty meet the professors oncologist...

Documents