cco clinoncjune2011 highlights slides 1

June 3-7, 2011Chicago, Illinois

Highlights From the 2011 Clinical Oncology Meeting CCO Independent Conference Coverageof the 2011 ASCO Annual Meeting*

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clinicaloptions.com/oncologyClinical Oncology 2011

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Faculty

Axel Grothey, MDProfessor, Oncology Mayo Clinic Rochester, Minnesota

John M. Kirkwood, MDProfessor, Medicine, Dermatology, and Translational Science Director, Melanoma and Skin Cancer Program University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania

Kathy D. Miller, MDAssociate Professor Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana

Craig Reynolds, MDDevelopment Chair US Oncology Lung Cancer Committee US Oncology Ocala, Florida


Faculty

David I. Quinn, MD, PhDAssociate Professor of Medicine Division of Cancer Medicine and Blood DiseasesThe University of Southern California Medical Director USC Norris Cancer Center and Hospital Los Angeles, California

Robert M. Rifkin, MD, FACPRocky Mountain Cancer Centers Denver, Colorado

Brian I. Rini, MDStaff Physician Department of Solid Tumor Oncology and UrologyCleveland Clinic Taussig Cancer Institute Associate Professor of Medicine CCF/CWRU Lerner College of Medicine Cleveland, Ohio

Nicholas J. Vogelzang, MDChair and Medical Director Developmental Therapeutics CommitteeUS Oncology ResearchComprehensive Cancer Centers of NevadaProfessor of MedicineUniversity of Nevada School of MedicineLas Vegas, Nevada


Faculty Disclosures

Axel Grothey, MD, has disclosed that he has received contracted research support from Bayer, Daiichi, and Genentech.

John M. Kirkwood, MD, has disclosed that he has received consulting fees from GlaxoSmithKline, Merck, and Morphotek.

Kathy D. Miller, MD, has disclosed that she has received consulting fees and fees for non-CME/CE services from Genentech.

Craig Reynolds, MD, has disclosed that he has received consulting fees from Genentech and Pfizer and fees for non-CME/CE services from Eisai and Eli Lilly.

David I. Quinn, MD, PhD, has disclosed that he has received consulting fees from Astellas, Bayer, Dendreon, Genomic Health, Novartis, Onyx, Johnson & Johnson, and Pfizer.


Faculty Disclosures

Robert M. Rifkin, MD, FACP, has disclosed that he has received consulting fees from Amgen, Celgene, Cephalon, Millennium, and Onyx.

Brian I. Rini, MD, has disclosed that he has received consulting fees from Aveo, GlaxoSmithKline, and Pfizer and has received research contracts from GlaxoSmithKline and Pfizer.

Nicholas J. Vogelzang, MD, has disclosed that he has received research contracts from Bayer, Johnson & Johnson, and Tokai; has served as a consultant for Amgen, Bayer, Boehringer Ingelheim, Celgene, Cougar, Dendreon, Eisai, Genentech, GlaxoSmithKline, Johnson & Johnson, Mannkind, Novartis, Pfizer, Millennium, and Veridex; has served on speaker bureaus for Arqule, Bayer, Cougar, Dendreon, Eli Lilly, Genentech, Johnson & Johnson, Novartis, Pfizer, Quintiles, Research to Practice, sanofi-aventis, Veridex, and Wilex; and has received grants or support from Algeta, Arqule, Cougar, GlaxoSmithKline, Johnson & Johnson, Mannkind, Novartis, Pfizer, Millennium, Tokai, Veridex, and Wilex.


Overview of Tumor Types Covered in This Slideset Melanoma

Genitourinary Cancers

Thoracic Cancers

Breast Cancer

Gastrointestinal Cancer

Hematologic Malignancies

Sarcomas

Ovarian Cancer

Melanoma


BRIM3: Vemurafenib vs Dacarbazine in BRAF V600E–Positive Melanoma

Randomized, nonblinded phase III trial

OS, PFS improved in all prespecified subgroups (age, sex, stage, PS, LDH)

Chapman PB, et al. ASCO 2011. Abstract LBA4.

Patients with untreated, unresectable stage IIIc/IV melanoma and confirmed

BRAF V600E mutation

(N = 675)

Vemurafenib 960 mg PO BID(n = 337)

Dacarbazine 1000 mg/m2 q3w(n = 338)

Outcome Vemurafenib(n = 336)

Dacarbazine(n = 336)

HR (95% CI) P Value

Estimated 6-mo OS, % 84 64 0.37 (0.26-0.55) < .0001

Median PFS, mos 5.3 1.6 0.26 (0.20-0.33) < .0001

ORR, % 48.4 5.5

CR 0.9 0

PR 47.5 5.5


BRIM3: Safety

Most common toxicities requiring dose modification included arthralgia, rash, fatigue, photosensitivity, and increased LFT values

Discontinuation due to AEs low in vemurafenib and dacarbazine arms (6% vs 4%)

Grade 3/4 Adverse Event, % Vemurafenib(n = 336)

Dacarbazine(n = 282)

Rash 8 0

Increased liver function tests 7 1

Arthralgia 3 < 1

Photosensitivity 3 0

Fatigue 2 2

Nausea 1 2

Neutropenia < 1 8

Cutaneous squamous cell carcinoma 12 < 1

Keratoacanthoma 6 0

Skin papilloma < 1 0

Chapman PB, et al. ASCO 2011. Abstract LBA4.


MDX-024: Ipilimumab + Dacarbazine vs Dacarbazine in Unresectable Melanoma Phase III trial

Wolchok JD, et al. ASCO 2011. Abstract LBA5.

Patients with previously untreated unresectable stage IIIc/IV melanoma

(N = 502)

Ipilimumab 10 mg/kg q3w for 4 cycles +Dacarbazine 850 mg/m2 q3w for 8 cycles

(n = 250)

Placebo q3w for 4 cycles +Dacarbazine 850 mg/m2 Q3W for 8 cycles

(n = 252)

Wk 24

Ipilimumab10 mg/kg q12w

PlaceboQ12W

Induction Therapy Maintenance Therapy

Est

ima

ted

Su

rviv

al

(%)

504540353025201510

50

47.3

36.3

28.5

17.920.8

12.2

Yr 1 Yr 2 Yr 3

Ipilimumab + DTIC (n = 250)Placebo + DTIC (n = 252)

P = .0009 (HR: 0.72; 95% CI: 0.59-0.87)

mOS, Mos11.29.1


MDX-024: Median OS, PFS, and Response

*Primary endpoint.

Outcome Ipilimumab + Dacarbazine

(n = 250)

Placebo + Dacarbazine

(n = 252)

HR (95% CI) P Value

Median OS, mos* 11.2 9.1 0.72 (0.59-0.87) .0009

Median PFS, mos 2.8 2.6 0.76 (0.63-0.93) .006

Disease control rate, % 33.2 30.2

CR 1.6 0.8

PR 13.6 9.5

SD 18.0 19.8

PD 44.4 52.0

Median duration of response, mos

19.3 8.1

Wolchok JD, et al. ASCO 2011. Abstract LBA5.


MDX-024: Safety

Substantially more grade 3/4 adverse events in ipilimumab + dacarbazine arm

Select Adverse Event, %

Ipilimumab + Dacarbazine(n = 247)

Placebo + Dacarbazine(n = 251)

Total Grade 3/4 Total Grade 3/4

Diarrhea 36.4 4.0 24.7 0

Increased ALT 33.2 21.9 5.6 0.8

Increased AST 29.1 18.2 5.6 1.2

Pruritus 29.6 2.0 8.8 0

Rash 24.7 1.2 6.8 0

Colitis 4.5 2.0 0.4 0

Hypothyroidism 1.6 0 0.4 0

Thyroiditis 0.8 0 0 0

Hyperthyroidism 0.4 0 0.4 0Wolchok JD, et al. ASCO 2011. Abstract LBA5.


EORTC 18991: Long-term PegIFN alfa-2b in Stage III Melanoma Significant RFS benefit of peginterferon sustained at 7.6 yrs of follow-up

Most striking benefit in subset of sentinel-node positive patients with ulcerated primary tumors (improved RFS, DMFS, and OS)

Most common AEs did not worsen as treatment duration increased

Outcome (ITT) 2007 Evaluation 2011 Evaluation

HR (95% CI) P Value HR (95% CI) P Value

RFS 0.82 (0.71-0.96) .01 0.87 (0.76-1.00) .05

DMFS 0.88 (0.75-1.03) .11 0.93 (0.81-1.07) .33

OS 0.98 (0.82-1.16) .78 0.96 (0.82-1.11) .57

Grade 3 Events Occurring in > 5% of Patients, %

PegIFN Maintenance(n = 627)

Observation(n = 629)

Fatigue 14 1

Liver toxicity 10 1

Depression 6 < 1

Eggermont AM, et al. ASCO 2011. Abstract 8506b.


BRAF Inhibitor (GSK436) + MEK Inhibitor (GSK212) in BRAF-Mutated Melanoma Phase I/II

GSK436/GSK212 combination therapy generally well tolerated across all doses; treatment-related grade ≥ 3 events occurred in 19% of patients

Skin toxicity incidence compares favorably vs historical data

Active in patients who did not receive previous BRAF inhibitor therapy (n = 71)

Unconfirmed Response, %

GSK436/GSK212 Dose Level

75 mg BID/1 mg QD

(n = 6)

150 mg BID/1 mg QD(n = 22)

150 mg BID/1.5 mg QD

(n = 24)

150 mg BID/2 mg QD(n = 19)

Clinical benefit (CR + PR + SD)

100 95 96 100

Objective response (CR + PR)

67 77 50 74

CR 0 14 0 11

Infante JR, et al. ASCO 2011. Abstract CRA8503.

Genitourinary Cancers


AXIS: Randomized Phase III Trial, Axitinib vs Sorafenib in Refractory Metastatic RCC Primary endpoint: PFS Treatments generally well

tolerated; similar toxicity

– All-grade hypertension and hypothyroidism more common with axitinib

– All-grade hand-foot syndrome, rash, and alopecia more common with sorafenib

– Discontinuation due to treatment-related AEs

– 3.9% in axitinib group

– 8.2% in sorafenib group

Rini BI, et al. ASCO 2011. Abstract 4503. Reprinted with permission.

1.00.90.80.70.60.50.40.30.20.1

0

PF

S (

Pro

bab

ilit

y)

0 2 4 6 8 10 12 14 16 18 20

Mos

P < .0001 (log-rank)Stratified HR: 0.665(95% CI: 0.544-0.812)

AxitinibSorafenib

mPFS, Mos6.74.7

95% CI6.3-8.64.6-5.6

Pts at Risk, nAxitinib

Sorafenib361362

256224

202157

145100

9651

6428

3812

206

103

11

00


AXIS: PFS by Prognostic Factors and Baseline Characteristics Authors: data support axitinib as the standard second-line therapy for

advanced RCC

Rini BI, et al. ASCO 2011. Abstract 4503.

AxitinibBenefit

SorafenibBenefit

Baseline Factor n

ECOG PS 1ECOG PS 0

Sunitinib-containing regimenBevacizumab-containing regimenTemsirolimus-containing regimen

Cytokine-containing regimenWhite

NonwhiteMale

FemaleAge < 65Age ≥ 65

MSKCC favorableMSKCC intermediate/poor

AsiaEurope

North AmericaOther region

3273963895924

25154717652320047624730641715235718628

HR (95% CI)0.0 1.0 2.0 3.0


AXIS: Patient Reported Outcomes on QoL

Composite endpoint: time to deterioration (TTD)*

Patient-reported QoL (FKSI scores) similar for axitinib and sorafenib in AXIS trial

Axitinib associated with 17% reduction in risk of TTD

Authors conclude:

– TTD composite endpoint supports primary efficacy analysis

– Extending PFS in mRCC has QoL value

Cella D, et al. ASCO 2011. Abstract 4504. Reprinted with permission.

1.00.90.80.70.60.50.40.30.20.1

0

Su

rviv

al D

istr

ibu

tio

n F

un

ctio

n

0 2 4 6 8 10 12 14 16 20 24

Time to Composite (Mos)

P = .014†

(HR: 0.829; 95% CI: 0.701-0.981)

AxitinibSorafenib

Median TTD, Mos

3.12.8

95% CI2.8-4.52.7-3.0

18 22

*Death, disease progression, or decrease in FKSI-15 scores.† 1-sided P value.


COU-AA-301: Final Analysis, Evaluation of CTCs as Efficacy-Response Biomarker Absolute median OS benefit of abiraterone acetate increased from 3.9 to

4.6 mos vs placebo (15.8 vs 11.2 mos, respectively; HR 0.74; 95% CI: 0.638-0.859; P < .0001)

Survival benefit seen regardless of baseline CTC level

Higher CTC conversion rates (from ≥ 5 to < 5) with abiraterone

Scher HI, et al. ASCO 2011. Abstract LBA4517.

CTC Conversion, % AA + Prednisone Placebo + Prednisone

P Value

Wk 4 (n = 422) 42 14 <.0001

Wk 8 (n = 374) 50 17 <.0001

Wk 12 (n = 330) 48 17 <.0001

Median OS, Mos (95% CI) AA + Prednisone(n = 649)

Placebo + Prednisone(n = 323)

Favorable CTC (< 5 cells/ 7.5 mL blood) 22.1 (20.4-24.1) 19.7 (16.7-NE)

Unfavorable CTC (≥ 5 cells/7.5 mL blood) 10.9 (9.9-12.0) 8.2 (7.4-9.3)


Efficacy-Response Biomarker Panel, Potential Surrogate for OS in mCRPC Biomarker panel developed using pre- and posttreatment

factors strongly associated with OS

Authors suggest the initial biomarker panel with CTC and LDH was strongly associated with survival

Model Factors in Patients With BL CTC ≥ 5

HR (95% CI)* P Value*

Treatment 1.030 (0.773-1.372) .8371

Fold change in LDH 1.252 (1.047-1.497) .0135

Baseline LDH 3.036 (2.276-4.048) < .0001

CTC conversion 0.386 (0.284-0.527) < .0001

Baseline CTC 1.135 (0.987-1.306) .0747

*Adjusted for the biomarker panel.

Scher HI, et al. ASCO 2011. Abstract LBA4517.


COU-AA-301: Effect of Abiraterone Acetate on Pain Palliation and SREs Nearly one half of COU-AA-301 patients report significant pain at baseline

Pain Interference Abiraterone + Prednisone

(n = 797)

Placebo + Prednisone

(n = 398)

P Value

Palliation, % 59.2 38.0 .0004

Median time to palliation, mos 1.02 3.71 .0009

TTP (25th percentile), mos 9.27 4.57 .0019

Logothetis C, et al. ASCO 2011. Abstract 4520. Reprinted with permission.

155/349(44.4%)

44/163(27.0%)

Pat

ien

ts E

xper

ien

cin

g

Pal

lia

tio

n (

%)

70605040302010

0AA (n = 797) Placebo (n = 398)

Pts

No

t E

xp

erie

nc

ing

P

alli

ati

on

(%

)

100

80

60

40

20

00 3 6 129

Mos

PlaceboAA

Median: 10.25 mos

P = .0010 (log rank)

Median: 5.55 mos


COU-AA-301: Concluding Efficacy Results

Efficacy Measure Abiraterone + Prednisone

(n = 797)

Placebo + Prednisone

(n = 398)

P Value

Median OS, mos 14.8 10.9 < .0001

Confirmed PSA response, % 29.1 5.5 < .0001

Median radiographic PFS, mos 5.6 3.6 < .0001

Time to first SRE* (25th percentile), days

301 150 < .0001

*SRE defined as one or more of the following: pathologic fracture, spinal cord compression, palliative radiation, bone surgery.

de Bono JS, et al. N Engl J Med. 2011;364:1995-2005. Scher HI, et al. ASCO 2011. Abstract LBA4517. Logothetis C, et al. ASCO 2011. Abstract 4520.


Cabozantinib, Dual MET/VEGFR TKI, vs Placebo in mCRPC Phase II randomized

discontinuation trial

*At progression, patients on placebo could cross-over to cabozantinib (n = 14).

Lead-in StageCabozantinib

100 mg/day PO(n = 171)

Patients with mCRPC,

measurabledisease, and

mRECIST progression;

rising PSA only, not eligible

SD(n = 31)

12 wksCabozantinib

100 mg/day PO(n = 14)

Placebo daily(n = 17)

Until PD*

Randomization

PR or CR

(n = 79)

Open-Label ExtensionCabozantinib

100 mg/day PO

PD(n = 61)

Discontinue Cabozantinib

Hussain M, et al. ASCO 2011. Abstract 4516.


Cabozantinib vs Placebo in mCRPC: Efficacy and Safety

Authors: cabozantinib has substantial antitumor activity in progressive mCRPC

– Disease control, Wk 12: 68%

– Measurable disease regression: 74%

– Evidence of improvement on bone scan: 76%

– Pain improvement: 67%

– Moderate but manageable toxicity profile; similar to other TKIs

Hussain M, et al. ASCO 2011. Abstract 4516. Reprinted with permission.

-12 0 10 20 30 40 50 60

PFS per mRECIST, Post Randomization (Wks)

12-WkLead-in Stage

Pro

po

rtio

n

Pro

gre

ss

ion

Fre

e

1.00

0.75

0.50

0.25

Cabozantinib (n = 14)Placebo (n = 17)

HR 0.13; log-rank P value .0007

mPFS, Wks21 6


Oral 17,20-lyase inhibitor, TAK-700, in mCRPC: Endocrine Responses Phase II results from phase I/II study designed to evaluate

safety and tolerability of different doses of TAK-700 in men (N = 97) with mCRPC

TAK-700 decreased testosterone to < 2 ng/dL by Wk 12

TAK-700 increased ACTH by Wk 12, but decreased ACTH when combined with prednisone

TAK-700 ± prednisone increased corticosterone by Wk 12

– Increases in corticosterone less with TAK-700 + prednisone compared with TAK-700 alone

Agus DB, et al. ASCO 2011. Abstract 4531.


TAK-700 in mCRPC: PSA Response and Safety 53% with PSA decreases ≥ 50% at 12 wks

Serious AEs in 25 patients (26%): hypokalemia (n = 3), ARF (n = 3), pneumonia (n = 2), UTI (n = 2), hypotension (n = 2), neutropenia (n = 2), fatigue (n = 2)

TAK-700 active and tolerable given with or without prednisone, suggesting feasibility of a steroid-free regimen

X Previous ketoconazole therapy

Agus DB, et al. ASCO 2011. Abstract 4531. Reprinted with permission.

300 mg BID (n = 23)600 mg BID + prednisone (n = 26)

400 mg BID + prednisone (n = 24)600 mg QD AM (n = 24)

Treatment

275250225200175150125100

25

-25

-75

7550

0

-50

-100-125

PS

A C

han

ge

at

12 W

ks (

%)

x x xx

X x x x xx

x xx x

X x xx x x x x x


Single-Agent Volasertib in Recurrent, Metastatic Urothelial Cancer (N = 50) Volasertib: potent, selective inhibitor of polo-like kinase; generally well tolerated with favorable

adverse event profile

Outcome All Patients (N = 50)

Dose Escalation to 350 mg

No(n = 27)

Yes(n = 23)

Median response duration, wks (range)

30.1 (12.1-66)

27.1(26.6-27.6)

30.4(12.1-66.0)

Median PFS, wks (range) 6.1 5.9(5.1-6.4)

11.1(5.1-22.1)

3-mo PFS, % 32 22.2 43.5

6-mo PFS, % 22 14.8 30.4

Stadler WM, et al. ASCO 2011. Abstract 4567. Reprinted with permission.

70605040

20

0

-20

-40

-60

-80

30

10

-10

-30

-50

-70

-90

Ma

xim

um

Ch

an

ge

F

rom

Ba

se

lin

e i

n

Tu

mo

r S

ize

(%

)

Best overall response: PD PR SD


Everolimus generally well tolerated: fatigue, mucositis, and anorexia most common grade 1-2 toxicities

– Grade ≥ 3 adverse events in 29 of 45 (64%) evaluable patients

Potential association between p-4E BP1 expression and PFS at 2 months

Outcome Patients(n = 37)

Median OS, mos (95% CI) 10.3 (7.8-16.1)

Median PFS, mos (95% CI) 3.3 (2.1-3.7)

PFS at 2 mos, % 62

Everolimus in Recurrent Metastatic TCC of the Urothelium (N = 45)

Outcome, n p-4E BP1 Expression by IHC

≤ 1+(n = 12)

≥ 2+(n = 23)

PFS at ≥ 2 mos* 5 17

Progression at < 2 mos 7 6

*P = .08

Milowsky MI, et al. ASCO 2011. Abstract 4606.

Thoracic Cancers


Status of Actionable Driver Mutations in Lung Adenocarcinoma Tumor Specimens

Lung Cancer Mutation Consortium (LCMC) mutation testing

– Performed in CLIA-certified laboratories at LCMC sites

Physicians used data in real-time to guide therapeutic decisions for patients

– If EGFR mutation: give erlotinib

– If other mutation: recommend trial of agent specific for that target

54% incidence of single driver mutations among samples

– KRAS, EGFR, and EML4-ALK most common

Kris MG, et al. ASCO 2011. Abstract CRA7506. Reprinted with permission.

No mutation detected

KRAS (22%)

EGFR (17%)

EML4-ALK (7%)

Double mutants (3%)

BRAF (2%)

AKT1

NRAS

MEK1

MET AMP

HER2

PIK3CA


Rosell R, et al. ASCO 2011. Abstract 7503. Reprinted with permission.

EURTAC: Erlotinib vs Chemo in EGFR Mutation-Positive, Stage IIIB/IV NSCLC Phase III; significant benefit in PFS and with erlotinib vs chemotherapy

Erlotinib (n = 86)Chemotherapy (n = 87)

HR: 0.37 (95% CI: 0.25-0.54; log-rank P < .0001)

PF

S P

rob

abili

ty

1.0

0.8

0.6

0.4

0.2

00 3 6 9 12 15 18 21 24 27 30 33

Mos

5.2 9.7

Patients at Risk, nErlotinibChemo

8687

6349

5420

328

215

174

93

71

40

20

20

00


EURTAC: OS and PFS Across Patient Subgroups No significant difference in OS at interim analysis; data immature with high rate of

crossover (HR = 0.80; 95% CI: 0.47-1.37; P = .4170)

No PFS benefit of erlotinib vs chemotherapy among former smokers

Rosell R, et al. ASCO 2011. Abstract 7503.

0.1 0.2 0.4 0.6 0.81.0 1.5 2.0 4.0

Favors Erlotinib HR Favors Chemotherapy

All< 65 yrs≥ 65 yrs

MaleFemale

PS 0PS 1PS 2

Current smokerFormer smoker

Never smokerExon 19 deletionL858R mutation

HR (95% CI)0.37 (0.25-0.54)0.44 (0.25-0.75)0.28 (0.16-0.51)0.38 (0.17-0.84)0.35 (0.22-0.55)0.26 (0.12-0.59)0.37 (0.22-0.62)0.48 (0.15-1.48)0.56 (0.15-2.15)1.05 (0.40-2.74)0.24 (0.15-0.39)0.30 (0.18-0.50)0.55 (0.29-1.02)

n173858847

1265792241934

12011558


EURTAC: Response and Safety

CT-treated patients had increased frequency of:

– Grade 3/4 AEs (81% vs 45%)

– Dose modification or interruption due to treatment-related AE (47% vs 23%)

– Discontinuation due to treatment-related AE (14% vs 5%)

– Treatment-related serious AEs (16% vs 7%)

Response Outcome, %

Erlotinib(n = 86)

Chemo(n = 87)

Objective response 58 15

CR 2 0

PR 56 15

Disease control rate 79 66

SD 21 51

PD 7 13

No response assessed

14 22

Rosell R, et al. ASCO 2011. Abstract 7503.


PARAMOUNT: Maintenance Pem Following Induction With Pem/Platinum Double-blind phase III trial

Patients enrolled (n = 939), eligible for randomization after induction phase (n = 548; 539 randomized)

Reasons patients not randomized: progressive disease (n = 217) adverse event (n = 62), death (n = 56), other (n = 65)

Pemetrexed 500 mg/m2

+ Cisplatin 75 mg/m2

both administered onDay 1 of a 21-day cycle

(n = 939)

Previously untreated

advanced-stagenonsquamous

NSCLC

CR, PR,or SD

Pemetrexed 500 mg/m2 onDay 1 of a 21-day cycle

+ BSC(n = 359)

Placebo on Day 1 of a 21-day cycle

+ BSC(n = 180)

PDBoth arms received folic acid

and vitamin B12 therapy

Induction phase (4 cycles) Maintenance phase (until PD)21-42days

Paz-Ares LG, et al. ASCO 2011. Abstract CRA7510.


PARAMOUNT: Efficacy, Safety, and QoL

Pem + BSCPlacebo + BSC

1.0

0.8

0.6

0.4

0.2

0.0

0 3 6 9 12 15Mos

Unadjusted HR: 0.62 (95% CI: 0.49-0.79; log-rank P = .00006)

Pts at Risk, nPem + BSC

Placebo + BSC359180

13252

5715

215

40

00

mPFS, Mos4.1 2.8

Improved disease control rate with pemetrexed vs placebo maintenance

– 71.8% vs 59.6%, respectively (P = .009)

Pemetrexed safety profile similar to previous reports

– However, significantly more drug-related serious AEs with pemetrexed vs placebo (8.9% vs 2.8%; P ≤ .05)

No significant difference in health-related QoL between arms

OS data not yet mature

Paz-Ares LG, et al. ASCO 2011. Abstract CRA7510.


MetMAb + Erlotinib vs Erlotinib Alone in Previously Treated Advanced NCSLC

MetMAb: monovalent antibody to Met

– Prevents Met activation by hepatocyte growth factor

EGFR mutations in study population

– Met diagnostic-positive population: imbalanced on MetMAb arm

– Met diagnostic-negative population: imbalanced on placebo arm

Predefined Met diagnostic-positive population

– Tumor samples with ≥ 50% tumor cells displaying moderate or strong Met staining by IHCSpigel DR, et al. ASCO 2011. Abstract 7505.

Reprinted with permission.

Growth Migration Survival

Noactivity

Met Met

HGF HGF

MetMAb


MetMAb + Erlotinib vs Erlotinib in Advanced NCSLC: PFS and OS No PFS or OS benefit to adding MetMAb to erlotinib in ITT population MetMAb + erlotinib associated with survival benefits in Met-positive

population

Outcome ITTPopulation(n = 137)

Met Diagnostic-Positive Population

(n = 66)

Met Diagnostic-Negative Population

(n = 62)

MetMAb+ Erlotinib

(n = 69)

Placebo+ Erlotinib

(n = 68)

MetMAb+ Erlotinib

(n = 35)

Placebo+ Erlotinib

(n = 31)

MetMAb+ Erlotinib

(n = 31)

Placebo+ Erlotinib

(n = 31)

Median PFS, mos 2.2 2.6 2.9 1.5 1.4 2.7

HR (95% CI) 1.09 (0.73-1.62) 0.53 (0.28-0.99) 1.82 (0.99-3.32)

P value .69 .04 .05

Median OS, mos 8.9 7.4 12.6 3.8 8.1 15.3

HR (95% CI) 0.80 (0.50-1.28) 0.37 (0.19-0.72) 1.78 (0.79-3.99)

P value .34 .002 .16

Spigel DR, et al. ASCO 2011. Abstract 7505.


MetMAb: Safety and Met Expression as a Prognostic Factor AE profile in MetMAb + erlotinib arm similar to placebo + erlotinib

– Higher frequency of peripheral edema in MetMAb arm

Met expression associated with worse outcome in placebo + erlotinib arm– 52% of tissue samples found to be Met diagnostic positive

Outcome Placebo + Erlotinib

Met Diagnostic Positive (n = 66)

Met Diagnostic Negative (n = 62)

Median PFS, mos 1.5 2.7

HR (95% CI) 1.71 (0.96-3.02)

P value .06

Median OS, mos 3.8 15.3

HR (95% CI) 2.61 (1.34-5.09)

P value .004Spigel DR, et al. ASCO 2011. Abstract 7505.


Retrospective Analysis of Crizotinib vs Comparable Controls in ALK+ NSCLC Median OS not yet reached in ALK+ crizotinib-treated patients from phase I study

(N = 82): 1-yr OS: 74%; 2-yr OS: 54%

OS significantly prolonged in ALK+ crizotinib-treated pts vs ALK+ crizotinib-naive controls (clinically and geographically comparable historic controls)

– ALK-positive status did not confer favorable prognosis

OS Outcome ALK+/Crizotinib(n = 30)

ALK+/Control(n = 23)

WT/Control(n = 125)

Median OS, mos NR 6 11

1-yr OS, % 70 44 47

2-yr OS, % 55 12 32

HR vs ALK/control 0.36

P value .004

HR vs WT/control 0.49 1.42

P value .02 .18

Shaw AT, et al. ASCO 2011. Abstract 7507.


Second-line Amrubicin vs Topotecan in Patients With SCLC (N = 637) Randomized phase III trial

Eligibility: response to platinum-based chemo followed by progression in ≥ 90 days (platinum sensitive) or < 90 days (platinum refractory)

Safety: lower incidence of hematologic events with amrubicin vs topotecan; more FN and infections (specifically pneumonia) observed with amrubicin, which did not translate to increased death

QoL significantly favored amrubicin vs topotecan

Outcome Amrubicin(n = 424)

Topotecan(n = 213)

HR (95% CI) P Value

Median OS, mos 7.5 7.8 0.880 (0.733-1.057) .1701

Platinum sensitive 9.2 9.9 0.936 (0.724-1.211) .6164

Platinum refractory 6.2 5.7 0.766 (0.589-0.997) .0469

Median PFS, mos 4.1 3.5 0.802 (0.667-0.965) .0182

Jotte R, et al. ASCO 2011. Abstract 7000.


RTOG 0522: Frontline Cisplatin/RT ± Cetuximab in Stage III/IV HNSCC Randomized phase III trial No statistical difference in

2-yr PFS (primary endpoint) or 2-yr OS between treatment arms

– PFS—HR: 1.05 (95% CI: 0.84-1.29; P = .66)

– OS—HR: 0.87 (95% CI: 0.66-1.15; P = .17)

Ang KK, et al. ASCO 2011. Abstract 5500.

63.4

82.6

64.3

79.7

0

20

40

60

80

100

2-Yr PFS 2-Yr OS

Cetuximab + cisplatin/RTCisplatin/RT

Su

rviv

al (

%)


RTOG 0522: Progression, Safety, and Survival by p16 Status

Risk of distant metastasis at 2 yrs—HR: 0.74 (95% CI: 0.49-1.11; P = .07)

Local-regional progression at 2 yrs—HR: 1.21 (95% CI: 0.92-1.60; P = .92)

Grade 3/4 skin reactions and mucositis ↑ with cetuximab

Late toxicity similar between arms

Survival similar by p16 gene expression

Ang KK, et al. ASCO 2011. Abstract 5500.

24.5

7.6

19.812.0

0

20

40

60

80

100

2-Yr LocoregionalProgression

2-Yr Distant

Metastasis

Cetuximab + cisplatin/RTCisplatin/RT

Rat

e (%

)


Incidence of Oropharyngeal Cancers Attributed to HPV Infection Oropharyngeal cancer cases from 1984 to 2004 identified in 3

SEER programs (Hawaii, Iowa, and Los Angeles)

From 1998-2004, incidence of HPV-positive oropharyngeal cancers increased by 225%, whereas incidence of HPV-negative oropharyngeal cancers decreased by 50%

Median survival significantly greater for patients with vs without HPV infection (131 vs 20 mos; P < .001)

Survival of all oropharyngeal cancer cases significantly increased over time (P < .001)

Authors suggest that the growing burden of HPV-positive oropharyngeal cancers emphasizes need to evaluate benefit of HPV vaccination for preventing oral HPV infection

Chaturvedi A, et al. ASCO 2011. Abstract 5529.

Breast Cancer


TBCRC 006: Neoadjuvant Lapatinib + Trastuzumab in HER2-Overexpressing BC Multicenter, phase II: N = 66; n = 64 evaluable for

response

Lapatinib 1000 mg/day + trastuzumab 2 mg/kg/wk (load: 4 mg/kg) for 12 wks followed by surgery

– ER+ disease also treated with letrozole (+ goserelin if premenopausal)

Chang JCN, et al. ASCO 2011. Abstract 505.

Pathologic Response, % All ER Positive ER Negative

pCR* 28 21 40

pCR* + npCR† 53 56 48

*pCR defined as no invasive cancer in breast. †npCR defined as < 1 cm residual disease in breast.


TBCRC 006 vs Other Neoadjuvant Trials in HER2-Positive Disease

1. Chang JCN, et al. ASCO 2011. Abstract 505. 2. Baselga J, et al. SABCS 2010. Abstract S3-3. 3. Gianni L, et al. SABCS 2010. Abstract S3-2. 4. Untch M, et al. SABCS 2010. Abstract S3-1.

Study and Treatment Pts, n pCR,* %

TBCRC 006[1]

Lapatinib + trastuzumab for 12 wks 66 28

NeoALTTO[2]

Lapatinib 18 wks with paclitaxel added for last 12 wksTrastuzumab 18 wks with paclitaxel added for last 12 wksLapatinib + trastuzumab 18 wks with paclitaxel added for last 12 wks

455154149152

24.729.551.3

NeoSphere[3]

Trastuzumab + docetaxel for 12 wksPertuzumab + docetaxel for 12 wksTrastuzumab + pertuzumab + docetaxel for 12 wksTrastuzumab + pertuzumab for 12 wks

10796

107107

29.024.045.816.8

Geparquinto (GBG 44)[4]

Lapatinib + epirubicin/cyclophosphamide → docetaxel for 24 wks Trastuzumab + epirubicin/cyclophosphamide → docetaxel for 24 wks

615308307

35.250.4

*No invasive cancer in breast.


NCIC CTG MAP.3: Placebo vs Exemestane to Prevent BC in Postmenopausal Women Double-blind phase III trial

Primary endpoint: incidence of invasive breast cancer

Annual incidence rate of invasive breast cancer

– Exemestane: 0.19% (95% CI: 0.08-0.30)

– Placebo: 0.55% (95% CI: 0.36-0.73)

– HR: 0.35 (95% CI: 0.18-0.70; P = .002)

Significant reduction in risk of invasive breast cancer with exemestane observed in patients with ER+, PgR+, and/or HER2-negative disease

– Investigators: findings should be interpreted with caution given small number of events

Incidence of DCIS and precancerous benign lesions also reduced

Goss PE, et al. ASCO 2011. Abstract LBA504. Goss, PE, et al. N Engl J Med. 2011;364:2381-2391.


NCIC CTG MAP.3: Safety

No increase in incidence of SAEs with exemestane over 3 yrs, including fractures, osteoporosis, CV toxicity, or second malignancies

Authors conclude: exemestane is an option for prevention of breast cancer in postmenopausal women

Goss PE, et al. ASCO 2011. Abstract LBA504. Goss, PE, et al. N Engl J Med. 2011;[Epub ahead of print].

Adverse Event (All Grades), % Exemestane (n = 2240) Placebo (n = 2248) P Value

Hot flashes 40 32 < .0001

Joint pain 30 27 .04

Fatigue 23 21 .03

Vaginal dryness 16 15 .68

Arthritis 11 9 .01

Depression 11 10 .96

Insomnia 10 8 .04

Muscle pain 7 9 .01

Nausea 7 5 .04

Diarrhea 5 3 .002


SWOG S0221: Cont. Wkly AC + Filgrastim vs q2w AC + Pegfilgrastim as Adjuvant Tx Phase III; current analysis compares continuous wkly AC + G vs AC q2w

Budd GT, et al. ASCO 2011. Abstract 1004.

Patients with stage I-III, node-positive or high-risk node-negative invasive

breast cancer who underwent surgical

resection

(N = 2716)

AC q2w*(n = 1375)

AC + G†

(n = 1341)

Paclitaxel 175 mg/m2 +Pegfilgrastim q2w for 6 cycles

Paclitaxel 175 mg/m2 +Pegfilgrastim q2w for 6 cycles

Paclitaxel 80 mg/m2/wkfor 12 cycles

Paclitaxel 80 mg/m2/wkfor 12 cycles

*AC q2w: doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 + pegfilgrastim, q2w for 6 cycles.†AC + G: doxorubicin 24 mg/m2 + cyclophosphamide 60 mg/m2 PO + granulocyte-colony stimulating factor (ie, filgrastim) on Days 2-7, wkly for 15 cycles.


SWOG S0221: DFS

Primary endpoint: DFS First interim analysis: lower 99.5% CI boundary of 0.82 crossed in AC + G arm, resulting in futility of AC + G vs AC q2w

– DSMB recommended halting randomization to AC wkly

Study still ongoing to assess whether weekly paclitaxel superior to q2w paclitaxel

Budd GT, et al. ASCO 2011. Abstract 1004. Reprinted with permission.

DF

S

Yrs Since Registration

AC q2w (n = 1342; 183 events)AC + G (n=1320; 202 events)

HR = 1.15 (95% CI: 0.95-1.41) P = .16

0 2 4 6 8

0

0.25

0.50

0.75

1.00

5-Yr DFS, %8279

0.50


SWOG S0221: Safety

Toxicity profiles of AC + G vs AC q2w differed

Budd GT, et al. ASCO 2011. Abstract 1004.

Grade 3/4 Adverse EventDuring AC Segments, %

AC + G AC q2w P Value

Anemia 5.25 9.6 < .001

Leukopenia 15.0 20.0 .001

Neutropenia 23.0 26.0 .09

Thrombocytopenia 3.4 2.8 .6

InfectionFebrile neutropeniaNonneutropenic

2.02.7

6.02.9

< .001.84

CardiotoxicityDuring AC segmentsDuring AC and paclitaxel segments

0.40.5

1.12.2

.046< .001

Mucositis 8.2 2.0 < .001

Dermatologic/hand-foot syndrome 17.0 2.0 < .001


Phase III: Addition of Iniparib (BSI-201) to Gemcitabine/Carboplatin in mTNBC Coprimary endpoints: OS and PFS

O’Shaughnessy J, et al. ASCO 2011. Abstract 1007. Reprinted with permission.

1.0

PF

S P

rob

abil

ity

0 2 4 6 80

Mos 10 12 14 16

0.8

0.6

0.4

0.2

OS

Pro

bab

ilit

y0 2 4 6 8

0

1.0

Mos10 12 14 16

0.8

0.6

0.4

0.2

Outcome, Mos GCI (n = 261) GC (n = 258) HR (95% CI) P Value

Median PFS 5.1 4.1 0.79 (0.65-0.98) .027

Median OS 11.8 11.1 0.88 (0.69-1.12) .28


Addition of Iniparib (BSI-201) to Gemcitabine/Carboplatin in mTNBC Addition of iniparib to GC in patients with mTNBC did not significantly

improve OS or PFS vs GC alone[1]

– OS findings may be confounded by 96% cross-over from control to experimental arm

– Results in contrast with those of previous phase II study[2]

ORR also similar with iniparib + GC vs GC alone: 34% vs 30%[1]

Exploratory analyses suggest iniparib may confer benefits in patients receiving iniparib + GC in second- and third-line settings[1]

– Confirmatory study needed

Biomarker analyses under way to identify potential patient subgroups that may benefit from iniparib

1. O’Shaughnessy J, et al. ASCO 2011. Abstract 1007. 2. O’Shaughnessy J, et al. N Engl J Med. 2011;364:205-214.


AMG 386 + Paclitaxel + Bevacizumab for First-line Tx of HER2-Negative Advanced BC Double-blind, randomized phase II study; primary endpoint: PFS comparison

of blinded arms– AMG 386: recombinant peptide-Fc fusion protein that binds and neutralizes effects

of Ang1 and Ang2 to inhibit angiogenesis

Dieras V, et al. ASCO 2011. Abstract 544. Reprinted with permission.

100

PF

S (

%)

80

60

40

20

00 5 10 15 20 25 30

Mos

mPFS, Mos11.39.2

12.2

AMG 386 10 mg/kg qw + P + Bev (n = 56)AMG 386 3 mg/kg qw + P + Bev (n = 57)Placebo qw + P + Bev (n = 58)

HR for AMG 386 10 mg/kg vs placebo: 0.984 (80% CI: 0.720-1.344; P = .946)

HR for AMG 386 3 mg/kg vs placebo: 1.119 (80% CI: 0.821-1.524; P = .642)


AMG 386 3 mg/kg

AMG 386 10 mg/kg

Placebo Open-LabelAMG386 10 mg/kg

+ Paclitaxel

CR

Pat

ien

ts (

%)

PR

SD

PD

NE/NA

12.2 2.4 10.9

10.2

2.4 4.8

13

26.5

24.431

30.4

49

63.4

59.541.3

2 7.3 4.3

0

20

40

60

80

100

+ Paclitaxel + Bevacizumab

cORR:51%

cORR:70.7%

cORR:59.5%

cORR:45.7%

Dieras V, et al. ASCO 2011. Abstract 544.

4.8

AMG 386 + Paclitaxel + Bevacizumab for First-line Tx of HER2-Negative Advanced BC

Gastrointestinal Cancer


Panitumumab + Rilotumumab or Ganitumab for mCRC With WT KRAS Rilotumumab: fully human HGF mAb Ganitumab: fully human IGF-1R mAb Phase Ib: DLT assessed Phase II: randomized comparison

Primary endpoint: ORR Probability that combination better

than panitumumab alone– Panitumumab + rilotumumab: 93%

– Panitumumab + ganitumab: 63%

Eng C, et al. ASCO 2011. Abstract 3500.

Response, % Panitumumab + Rilotumumab*

(n = 48)

Panitumumab + Ganitumab*

(n = 46)

Panitumumab + Placebo* (n = 48)

ORR 31 22 21

CR 0 0 0

PR 31 22 21

SD 40 39 35

PD 23 33 33

*Panitumumab dosed at 6 mg/kg, rilotumumab dosed at 10 mg/kg, and ganitumab dosed at 12 mg/kg; all doses administered q2w.


Panitumumab + Rilotumumab or Ganitumab: Adverse EventsGrade 3/4 Adverse Event,* %

Panitumumab + Rilotumumab (n = 48)

Panitumumab + Ganitumab (n = 46)

Panitumumab + Placebo (n = 48)

Any 71 63 52

Rash 29 13 8

Acneiform dermatitis 15 11 10

Hypomagnesemia 4 15 2

Abdominal pain 4 7 6

Anemia 0 0 8

Constipation 0 0 6

Acne 4 0 0

Asthenia 0 4 0

Diarrhea 4 2 0

Fatigue 4 2 2

Paronychia 4 2 2

Skin toxicity 2 4 0

*Occurring in > 2% of patients in any treatment arm.

Eng C, et al. ASCO 2011. Abstract 3500.


Impact of KRAS G13D Mutation in CRYSTAL and OPUS Trials CRYSTAL and OPUS: improved efficacy with addition of

cetuximab to first-line chemotherapy in KRAS WT mCRC[1]

– Patients with KRAS mutated mCRC experienced either no benefit or worse outcomes with cetuximab + first-line chemotherapy

KRAS G13D mutated cells sensitive to cetuximab[2]

In pooled exploratory analysis of CRYSTAL and OPUS, KRAS G13D mutation associated with poor prognosis in chemotherapy alone arms from each trial[3]

– PFS HR for KRAS G13D vs other mutations: 1.54 (P = .0847)

– OS HR for KRAS G13D vs other mutations: 1.39 (P = .0988)

1. Bokemeyer C, et al. ASCO 2010. Abstract 3506. 2. De Roock W, et al. JAMA. 2010;304:1812-1820. 3. Tejpar S, et al. ASCO 2011. Abstract 3511.


Impact of KRAS G13D Mutation in CRYSTAL and OPUS Trials Significant treatment interaction observed for KRAS G13D vs KRAS

other mutations

– PFS: P < .0001; OS: P = .0201; response: P < .0001

Similar treatment effects for KRAS G13D mutations and KRAS WT

*HR for PFS and OS outcomes; OR for response rate outcomes; HR < 1 favors chemotherapy + cetuximab and HR > 1 favors chemotherapy alone; OR < 1 favors chemotherapy alone and OR > 1 favors chemotherapy + cetuximab.

Tejpar S, et al. ASCO 2011. Abstract 3511.

HR or OR* in Pooled Analysis (95% CI)

KRASWT

KRAS G13D KRAS G12V KRASOther Muts

Median PFS 0.66(0.55-0.80)

0.60(0.32-1.12)

1.55(0.94-2.56)

1.37(1.02-1.84)

Median OS 0.81(0.69-0.94)

0.80(0.49-1.30)

1.10(0.75-1.62)

1.16(0.91-1.48)

Response rate 2.17(1.64-2.86)

2.41(0.90-6.45)

0.54(0.26-1.12)

0.58(0.36-0.91)


NSABP R-04: Neoadjuvant Capecitabine and Oxaliplatin for Rectal Cancer Phase III trial; patients with

resectable stage II/III rectal cancer randomized to 1 of 4 arms

– 5-FU: n = 477

– 5-FU + oxaliplatin: n = 329

– Capecitabine: n = 472

– Capecitabine + oxaliplatin: n = 330

All pts received neoadjuvant radiation in addition to CT

Primary endpoint: locoregional relapse rate (data not yet mature)

Outcome, % 5-FU Capecitabine P Value

pCR 18.8 22.2 .12

SD 20.7 23.0 .62

SSS 61.2 62.7 .59

5-FU vs capecitabine

Outcome, % No Oxaliplatin

Oxaliplatin P Value

pCR 19.1 20.9 .46

SD 23.0 19.2 .48

SSS 63.6 60.4 .28

Oxaliplatin vs no oxaliplatin

– More grade 3/4 diarrhea with oxaliplatin vs no oxaliplatin: 15.4% vs 6.6% (P = .0001)

Roh MS, et al. ASCO 2011. Abstract 3503.


CLASSIC: Adj. XELOX vs Observation After D2 Dissection of Gastric Cancer Primary endpoint: 3-yr DFS

– All pts in trial Asian; phase III

XELOX given for 8 cycles

3-yr DFS benefit maintained across subgroups: disease stage, age, nodal status

Nearly twice as many patients in observation vs XELOX arm experienced disease recurrence

– XELOX: 18.1%

– Observation: 30.1%

Trend toward prolonged OS with XELOX vs observation (median follow-up: 34.4 mos)

– HR: 0.74 (95% CI: 0.53-1.03; P = .0775)

Bang Y, et al. ASCO 2011. Abstract LBA4002. Reprinted with permission.

1.0

0.8

0.6

0.4

0.2

00 6 12 18 24 30 36 42 48

Mos

74%

60%

HR: 0.56 (95% CI: 0.44-0.72;P < .0001)

XELOX (n = 520)Observation (n = 515)

No. leftXELOX

Observation520515

443414

410352

333286

246209

166147

7458

3022

106


Adjuvant XELOX vs Observation After D2 Dissection of Gastric Cancer: AEs AEs markedly higher in XELOX vs observation arms

– All grades: 99% vs 52%; grade 3/4: 54% vs 6%; serious AEs: 14% vs 7%

AEs in XELOX Arm, % XELOX (n = 496)

All Grades Grade 3/4

Nausea 66 8

Neutropenia 60 22

Peripheral neuropathy 56 2

Diarrhea 47 2

Vomiting 39 7

Thrombocytopenia 26 8

Hand-foot syndrome 19 1

Stomatitis 12 < 1

Cardiac disorders 2 < 1

Bang Y, et al. ASCO 2011. Abstract LBA4002.


BSC ± Second-line Chemotherapy in Pretreated Advanced Gastric Cancer Phase III Korean trial

Chemotherapy: docetaxel or irinotecan; continued until PD, toxicity, or study withdrawal

Primary endpoint: OS

No significant difference in OS with docetaxel vs irinotecan (P = .114)

OS benefit maintained across patient subgroups

Park SH, et al. ASCO 2011. Abstract 4004. Reprinted with permission.

OS

Pro

bab

ility

0

0.2

0.4

0.6

0.8

1.0

Mos

Median f/u: 17 mos (95% CI: 16-18 mos)

Log rankP = .009

0 6 12 18

SLC + BSCBSC alone

Median5.1 mos3.8 mos

95% CI4.0-6.23.0-4.6


BSC ± Second-line Chemotherapy in Pretreated Advanced Gastric Cancer: AEs Similar incidence of all-cause death within 30 days of

randomization regardless of treatment

– Docetaxel: n = 1

– Irinotecan: n = 1

– BSC alone: n = 2

Park SH, et al. ASCO 2011. Abstract 4004.

Grade 3/4 AE, % SLC + BSC BSC Alone (n = 62)Docetaxel

(n = 66)Irinotecan

(n = 60)

Fatigue 17 20 27

Anorexia 6 5 10

Nausea 5 3 6

Diarrhea 3 8 5

Stomatitis 6 2 2

Hematologic Malignancies


COMFORT-II (Phase III): Ruxolitinib in Myelofibrosis Ruxolitinib (INCB18424): potent and selective JAK1/2 inhibitor

Primary endpoint: 35% reduction in spleen volume by MRI at Wk 48

Patients with myelofibrosis and

≥ 2 IPSS risk factors

(N = 219)

Ruxolitinib 15 or 20 mg PO BID

(n = 146)

Best Available Therapy (BAT)(n = 73)

Ruxolitinib extension or crossover if

disease progression*

Harrison CN, et al. ASCO 2011. Abstract LBA6501.

≥ 35% Reduction in Spleen Volume, % (95% CI)

Ruxolitinib(n = 146)

BAT(n = 73)

P Value

Wk 24 31.9 (24.4-40.2) 0 (0-5) < .0001

Wk 48 28.5 (21.3-36.6) 0 (0-5) < .0001

*Progression defined as splenectomy or 25% spleen volume increase from baseline or on-study nadir.


COMFORT-II: Survival and QoL

PFS, LFS, and OS did not significantly improve with ruxolitinib treatment Ruxolitinib associated with improvement in symptoms and functioning

Mean Change in EORTC QLQ-C30 Scores From Baseline to Wk 48

Ruxolitinib(n = 69)

BAT(n = 28)

Global health status or QoL 9.1 (n = 66) 3.4 (n = 27)

Role functioning 9.9 -5.4

Select symptoms common to myelofibrosis

Loss of appetite -8.2 9.5

Insomnia -12.3 (n = 68) 6.0

Dyspnea -6.3 4.8

Pain -1.9 3.0

Fatigue -12.8 0.4

Harrison CN, et al. ASCO 2011. Abstract LBA6501.


COMFORT-II: Safety and Conclusions

Grade 3/4 anemia (mostly grade 3) and thrombocytopenia (mostly grade 1/2) more common with ruxolitinib treatment

Results of phase III COMFORT-I[1] trial (N = 308) comparing ruxolitinib vs placebo similar to COMFORT-II[2]

– At Wk 24, 42% of ruxolitinib-treated patients had ≥ 35% reduction in spleen volume vs 0.7% of placebo-treated patients: OR: 134.4 (95% CI: 17.97-1005; P < .0001)

– Significantly more ruxolitinib-treated patients had ≥ 50% decrease in total symptom score vs placebo (46% vs 5%, respectively; P < .0001)

– As with COMFORT-II OS not statistically different between treatment arms (60-wk OS: 93.5% ruxolitinib vs 90.9% placebo)

Authors suggest ruxolitinib may be a significant improvement over currently available treatments for MF

1. Verstovsek S, et al. ASCO 2011. Abstract 6500. 2. Harrison CN, et al. ASCO 2011. Abstract LBA6501.


CLASSIC I: Clofarabine + Cytarabine vs Cytarabine in Relapsed/Refractory AML Poor prognosis for older patients (older than 55 yrs of age) with

relapsed or refractory AML

Efficacy Outcome, % Clofarabine + Cytarabine(n = 162)

Cytarabine Alone (n = 157)

P Value

4-mo EFS 38 17 < .0001

ORR 47 23 < .0001

CR 35 18 .0005

Faderl S, et al. ASCO 2011. Abstract 6503.

OS not significantly different between treatment arms

– Median OS: 6.6 mos for clofarabine + cytarabine vs 6.4 mos for cytarabine alone: HR: 1.00 (95% CI: 0.78-1.28; P = .9951)

Clofarabine + cytarabine associated with 47% reduced risk of events (progression or death): HR: 0.63 (95% CI: 0.49-0.80; P = .0001)


Decitabine vs SC or Cytarabine in Older Patients With Newly Diagnosed AML Open-label phase III trial; at protocol-defined clinical cutoff (396

deaths), median OS not statistically longer with decitabine (7.7 vs 5.0 mos; HR: 0.85; 95% CI: 0.69-1.04; P = .108)

Decitabine demonstrated significant benefit in OS for pts 75 yrs or older, de novo AML diagnosis, bone marrow blast > 30%, intermediate risk cytogenetics, ECOG PS 2

Higher response rates found with decitabine treatment vs either SC or low-dose cytarabine

> 50% of pts with treatment-related grade 3/4 adverse event; rates similar between decitabine and cytarabine treatment (low with SC)

Response, % Decitabine(n = 242)

Treatment Choice

(n = 243)

Low-Dose Cytarabine(n = 215)

Supportive Care

(n = 28)

CR + CR with incomplete platelet recovery 17.8* 7.8* 8.4 3.6

Thomas XG, et al. ASCO 2011. Abstract 6504.

*P = .001; OR: 2.5 (95% CI 1.40-4.78).


SWOG 9704: ASCT After R-CHOP in Pts With Advanced High-Risk Diffuse NHL Pts (N = 253) with ≥ PR after induction with CHOP ± R for 5 cycles

Randomized to R-CHOP for 1 cycle + ASCT or R-CHOP for 3 cycles

Higher incidence of grade 3/4 adverse events observed with ASCT

ASCT significantly prolonged PFS in patients with advanced high-intermediate or high IPI diffuse NHL

In exploratory analysis, significantly greater proportion of pts with a high IPI score had 2-yr PFS and OS with ASCT in first remission vs those with CHOP ± rituximab alone

Outcome, % CHOP ± R for 1 Cycle + ASCT(n = 125)

CHOP ± R for 3 Cycles (n = 128)

HR (95% CI) P Value

2-yr PFS 69 56 1.72 (1.18-2.51) .005

2-yr OS 74 71 1.24 (0.81-1.91) .16

Stiff PJ, et al. ASCO 2011. Abstract 8001.


Frontline R-MegaCHOEP and ASCT vs R-CHOEP-14 in B-Cell Lymphoma Younger (age < 61 yrs) high-risk pts (N = 262) with aggressive disease

Randomized to 8 cycles R-CHOEP-14 vs 4 cycles R-MegaCHOEP with ASCT

75% of pts achieved CR/CRu with no benefit of R-MegaCHOEP + ASCT over R-CHOEP-14

Grade 3/4 AEs more common with R-MegaCHOEP

R-MegaCHOEP followed by ASCT not superior R-CHOEP-14Outcome at Yr 3, % R-CHOEP-14 x 8 Cycles(n = 130)

R-MegaCHOEP + ASCT x 4 Cycles

(n = 132)

P Value

EFS 69.5 61.4 .140

aaIPI 2 75.5 63.5 .051

PFS 73.7 69.8

OS 84.6 77.0 .081

aaIPI 2 91.0 77.1 .013

Schmitz N, et al. ASCO 2011. Abstract 8002.


R-HDT vs R-CHOP-14 as First-line Treatment for Younger Pts With DLBCL

CHOP-14 + Rituximab 375 mg/m2

on Day 1(n = 156)

HDT + Rituximab 375 mg/m2

on Day 1(n = 156)

Adults (60 yrs of age or younger)

with DLBCL

(N = 312)

Stratified by center and age-adjusted IPI

4 cycles; evaluation

PET negR-CHOP-14

4 cycles

PET pos

PET neg

R-DHAP x 3BEAM

BEAM + ASCT

Le Gouill S, et al. ASCO 2011. Abstract 8003.


R-HDT vs R-CHOP-14: Results

Numerically more patients in R-CHOP-14 treatment arm PET-negative at intermediate evaluation compared with patients in R-HDT arm

ORR 88% for both treatment arms

Authors conclude that R-CHOP-14 for 8 cycles could become new standard in patients who are PET negative after 4 cycles

3-Yr Survival, % CHOP-14 + Rituximab(n = 156)

HDT + Rituximab(n = 156)

P Value

EFS 56 41 .03

Age-adjusted IPI 0-1 57 46 .3

Age-adjusted IPI 2-3 56 37 .06

PFS 81 79 .9

OS (median not reached) 85 82 NS

Le Gouill S, et al. ASCO 2011. Abstract 8003.


CORAL: Induction Therapy With R-ICE vs R-DHAP in Relapsed DLBCL Pts with CD20+ relapsed DLBCL randomized to salvage

with R-ICE vs R-DHAP each followed by BEAM and ASCT; pts with at least a PR randomized to observation or maintenance rituximab therapy for 1 yr

At a median follow-up of 45 mos, mobilization-adjusted ORR comparable after induction therapy

– 51.5% for R-ICE vs 56.5% for R-DHAP

– Fewer AEs with R-ICE

EFS and OS comparable between R-ICE and R-DHAP

– EFS: 29% vs 33%, respectively

– OS: 48% vs 51%, respectivelyGisselbrecht C, et al. ASCO 2011. Abstract 8004.


CORAL: Rituximab Maintenance Therapy vs Observation in Relapsed DLBCL EFS, PFS, and OS comparable with rituximab

maintenance vs no additional therapy

Median PFS longer for females vs males in rituximab maintenance arm

– Not reached vs 25.3 mos (P = .0044)

Survival After Maintenance Therapy, Mos

Maintenance Rituximab(n = 122)

No Additional Therapy(n = 120)

P Value

Median EFS 57.6 58.2 .7435

Median PFS 57.6 58.2 .8314

Median, mos Not reached 62.9 .7547

Gisselbrecht C, et al. ASCO 2011. Abstract 8004.


MM-015: SPM With MPR-R vs MPR vs MP in Elderly Pts With Newly Diagnosed MM

Patients (N = 459) aged 65 yrs or older randomized to MPR followed by maintenance lenalidomide vs MPR vs MP

Median PFS significantly prolonged in MPR-R arm (31 mos) vs MPR (14 mos) and MP (13 mos) arms

– Risk of PD reduced 60% in MPR-R arm vs MP (HR: 0.395; P < .001)

– No significant difference in OS among 3 treatment arms at median follow-up of 30 mos

8.0

5.9

2.6

4.7

3.3

0.7

3.32.6

2.0

0

2

4

6

8

10

MPR-R MPR MP

Total invasive SPMs

Hematologic malignancies

Solid tumors

Inci

den

ce

of

SP

Ms

(%)

Palumbo AP, et al. ASCO 2011. Abstract 8007.

Risk for PD or death greater than risk for SPM in each treatment arm


BiRD: SPM With Continuous Lenalidomide as First-line Therapy for MM Patients (N = 72) with newly diagnosed MM

Efficacy with 6 yrs of follow-up

– ORR: 90%; CR/near CR: 53%

– 2-yr EFS: 97.2%; 4-yr OS: 82%

Incidence of SPM following first-line treatment with BiRD: 11 of 68 pts (16%) with no cases of AML/MDS

Incidence of invasive cancer comparable to that of general population of similar age (SEER 2003-2007)

– Patients initially treated with BiRD: 2.85 per 100 person-yrs

– General population: 2.1 per 100 person-yrsRossi AC, et al. ASCO 2011. Abstract 8008.


MM-009/MM-010: Risk of SPM With LEN + DEX in Relapsed/Refractory MM Patients (N = 704) with relapsed/refractory MM randomized to

lenalidomide/dex vs placebo/dex

Incidence of invasive SPM (1.71 per 100 person-yrs) with lenalidomide/dex treatment; comparable to SEER data

No cases of AML; MDS: n = 2; solid tumors: n = 6 (heterogeneous)

Noninvasive nonmelanoma skin cancer reported in 11 patients receiving lenalidomide/dex and 2 patients receiving placebo/dex

Significantly longer median TTP or development of SPM with lenalidomide/dex vs placebo/dex (HR: 0.355; 95% CI: 0.292-0.431; P < .001)

Significantly longer median OS with lenalidomide/dex vs placebo/dex (HR: 0.607; 95% CI: 0.459-0.803; P < .001)

Dimopoulos MA, et al. ASCO 2011. Abstract 8009.


SPM Following Multiple Myeloma

Potential bias in evaluating SPM

– Reporting of SPM varies between treatment arms

– Often survival differences between treatment arms

– Differences in study design

Mechanism of SPM in MM currently unknown

Clinicians should weigh the demonstrated benefits of therapy with the risk of SPM

Landgren O. ASCO 2011. Discussant. Reprinted with permission.

Proposed Model for SPM Following MM

Treatment of MM

Secondmalignancy

Behavioralfactors

MM related factors

Host relatedfactors

Environmentalfactors

Sarcomas


SUCCEED: Ridaforolimus Maintenance in Patients With Metastatic Sarcoma Double-blind phase III trial

Ridaforolimus: oral rapamycin analogue with potent activity against mTOR

Primary endpoint (PFS) significantly prolonged vs placebo

Patients with metastatic sarcoma who had attained

CR, PR, or SD from previous standard

chemotherapy

(N = 711)

Ridaforolimus 40 mg PO QD for 5 days/wk(n = 347)

Placebo PO QD for 5 days/wk(n = 364)

Disease progression

or unacceptable

toxicity

Outcome, IRC Assessment Ridaforolimus(n = 347)

Placebo (n = 364)

HR P Value

Median PFS, wks 17.7 14.6 0.72 .0001

PFS rate, %

3 mos 70 54

6 mos 34 23

Chawla SP, et al. ASCO 2011. Abstract 10005.


SUCCEED: OS, Response, and Safety

Clinical benefit (CR + PR + SD ≥ 4 mos) significantly improved

Ridaforolimus safety profile consistent with that of other mTOR inhibitors

≥ 1 grade ≥ 3 AEs more common with ridaforolimus vs placebo (64% vs 26%)

Grade ≥ 3 events occurring more often with ridaforolimus included thrombocytopenia, stomatitis, anemia, hyperglycemia, infections, and diarrhea

Outcome Ridaforolimus(n = 347)

Placebo (n = 364)

HR P Value

Median OS, mos 21.4 19.2 0.88 .2256

Clinical benefit, % 40.6 28.6 -- .0009

Best target lesion response, mean tumor size %

-1.3 +10.3 -- < .0001

Chawla SP, et al. ASCO 2011. Abstract 10005.

Ovarian Cancer


OCEANS: Bev + Carboplatin/Gemcitabine in Recurrent Ovarian Cancer

Population Median PFS, Mos HR (95% CI) P Value

Bev + CG(n = 242)

Placebo + CG(n = 242)

Investigator assessed 12.4 8.4 0.484(0.388-0.605)

< .0001

IRC assessed 12.3 8.6 0.451 (0.351-0.580)

< .0001

Aghajanian C, et al. ASCO 2011. Abstract LBA5007.

Platinum-sensitive recurrent OC*

Measurable diseaseECOG 0/1No previous chemo forrecurrent OCNo previous Bev

(n = 484)

PL q3w until progression

Bev 15 mg/kg q3w until progression

CG + PL

CG + Bev

CG for 6 (up to 10) cycles

C AUC 4

G 1000 mg/m2 Days 1 & 8

C AUC 4

G 1000 mg/m2 Days 1 & 8

*Epithelial ovarian, primary peritoneal, or fallopian tube cancer.


OCEANS: OS, Response, and Safety

In interim analysis, trend toward improved OS; final OS results awaited

Safety profile of bev + carbo/gem consistent with other trials; serious AEs and more common with addition of bevacizumab

Similar incidence of ≥ grade 3 neutropenia in both arms; ≥ grade 3 hypertension and ≥ grade 3 proteinuria more common in bev arm

Aghajanian C, et al. ASCO 2011. Abstract LBA5007.

Outcome Bev + CG(n = 242)

Placebo + CG(n = 242)

HR (95% CI) P Value

Objective response, % 78.5 57.4 -- < .0001

CR 17 9

PR 61 48

Median duration of response, mos

10.4 7.4 0.534(0.408-0.698)

< .0001

Go Online for More CCO Coverage of Clinical Oncology

Data From Chicago!Capsule Summaries of all the key data presented at the 2011 conference

Expert Analyses panel discussions exploring the clinical implications of these key data

clinicaloptions.com/oncology

Conference Highlights reviewing the potential impact of these new findings on clinical practice

http://www.clinicaloptions.com/oncology

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