CCO ClinOncJune2011 Highlights Slides 1

Highlights From the 2011 Clinical Oncology Meeting
CCO Independent Conference Coverage

of the 2011 ASCO Annual Meeting*
June 3-7, 2011 Chicago, Illinois
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from This program is supported by an educational grant from
Clinical Oncology 2011

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Faculty
Axel Grothey, MD
Professor, Oncology Mayo Clinic Rochester, Minnesota
Kathy D. Miller, MD
Associate Professor Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana
John M. Kirkwood, MD
Professor, Medicine, Dermatology, and Translational Science Director, Melanoma and Skin Cancer Program University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania
Craig Reynolds, MD
Development Chair US Oncology Lung Cancer Committee US Oncology Ocala, Florida

Faculty
David I. Quinn, MD, PhD
Associate Professor of Medicine Division of Cancer Medicine and Blood Diseases The University of Southern California Medical Director USC Norris Cancer Center and Hospital Los Angeles, California
Brian I. Rini, MD
Staff Physician Department of Solid Tumor Oncology and Urology Cleveland Clinic Taussig Cancer Institute Associate Professor of Medicine CCF/CWRU Lerner College of Medicine Cleveland, Ohio
Robert M. Rifkin, MD, FACP

Rocky Mountain Cancer Centers Denver, Colorado
Nicholas J. Vogelzang, MD
Chair and Medical Director Developmental Therapeutics Committee US Oncology Research Comprehensive Cancer Centers of Nevada Professor of Medicine University of Nevada School of Medicine Las 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 V600EPositive Melanoma

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)
Randomized, nonblinded phase III trial OS, PFS improved in all prespecified subgroups (age, sex, stage, PS, LDH)
Vemurafenib (n = 336) 84 5.3 48.4 0.9 Dacarbazine (n = 336) 64 1.6 5.5 0 HR (95% CI) 0.37 (0.26-0.55) 0.26 (0.20-0.33) P Value < .0001 < .0001
Outcome Estimated 6-mo OS, % Median PFS, mos ORR, % CR
PR
47.5
5.5
Chapman PB, et al. ASCO 2011. Abstract LBA4.

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%)
Vemurafenib (n = 336) 8 7 3 3 2 1 <1 12 6 <1 Dacarbazine (n = 282) 0 1 <1 0 2 2 8 <1 0 0
Grade 3/4 Adverse Event, % Rash Increased liver function tests Arthralgia Photosensitivity Fatigue Nausea Neutropenia Cutaneous squamous cell carcinoma Keratoacanthoma Skin papilloma Chapman PB, et al. ASCO 2011. Abstract LBA4.

MDX-024: Ipilimumab + Dacarbazine vs Dacarbazine in Unresectable Melanoma

Phase III trial
Patients with previously untreated unresectable stage IIIc/IV melanoma (N = 502) 50 45 40 35 30 25 20 15 10 5 0 Estimated Survival (%) Induction Therapy Wk 24 Maintenance Therapy Ipilimumab 10 mg/kg q3w for 4 cycles + Dacarbazine 850 mg/m2 q3w for 8 cycles (n = 250) Ipilimumab 10 mg/kg q12w Placebo Q12W
Placebo q3w for 4 cycles + Dacarbazine 850 mg/m2 Q3W for 8 cycles (n = 252)
47.3 36.3 28.5 17.9 20.8 12.2
mOS, Mos 11.2 Ipilimumab + DTIC (n = 250) 9.1 Placebo + DTIC (n = 252) P = .0009 (HR: 0.72; 95% CI: 0.59-0.87)
Yr 1 Yr 2 Wolchok JD, et al. ASCO 2011. Abstract LBA5.
Yr 3

MDX-024: Median OS, PFS, and Response

Outcome Ipilimumab + Dacarbazine (n = 250) 11.2 2.8 33.2 1.6 13.6 18.0 44.4 19.3 Placebo + Dacarbazine (n = 252) 9.1 2.6 30.2 0.8 9.5 19.8 52.0 8.1 HR (95% CI) P Value
Median OS, mos* Median PFS, mos Disease control rate, % CR PR SD PD Median duration of response, mos *Primary endpoint.
0.72 (0.59-0.87) 0.76 (0.63-0.93)
.0009 .006
Wolchok JD, et al. ASCO 2011. Abstract LBA5.

MDX-024: Safety
Substantially more grade 3/4 adverse events in ipilimumab + dacarbazine arm
Ipilimumab + Dacarbazine (n = 247) Placebo + Dacarbazine (n = 251) Select Adverse Event, %
Total
Diarrhea Increased ALT Increased AST Pruritus Rash Colitis Hypothyroidism Thyroiditis Hyperthyroidism 36.4 33.2 29.1 29.6 24.7 4.5 1.6 0.8 0.4
Grade 3/4
4.0 21.9 18.2 2.0 1.2 2.0 0 0 0
Total
24.7 5.6 5.6 8.8 6.8 0.4 0.4 0 0.4
Grade 3/4
0 0.8 1.2 0 0 0 0 0 0
Wolchok 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)
2007 Evaluation HR (95% CI) RFS DMFS OS 0.82 (0.71-0.96) 0.88 (0.75-1.03) 0.98 (0.82-1.16) P Value .01 .11 .78 2011 Evaluation HR (95% CI) 0.87 (0.76-1.00) 0.93 (0.81-1.07) 0.96 (0.82-1.11) P Value .05 .33 .57
Outcome (ITT)
Most common AEs did not worsen as treatment duration increased

PegIFN Maintenance (n = 627)
14 10 6
Grade 3 Events Occurring in > 5% of Patients, %

Fatigue Liver toxicity Depression Eggermont AM, et al. ASCO 2011. Abstract 8506b.
Observation (n = 629)
1 1 <1

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)
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)
Unconfirmed Response, %
Clinical benefit (CR + PR + SD)

Objective response (CR + PR) CR
100
67 0
95
77 14
96
50 0
100
74 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
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0
0 2 4 6 mPFS, Mos Axitinib 6.7 Sorafenib 4.7 95% CI 6.3-8.6 4.6-5.6
Treatments generally well tolerated; similar toxicity

All-grade hypertension and hypothyroidism more common with axitinib
PFS (Probability)
P < .0001 (log-rank) Stratified HR: 0.665 (95% CI: 0.544-0.812)
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
Pts at Risk, n Axitinib 361 256 202 145 Sorafenib 362 224 157 100
10 12 Mos
64 28 38 12
14
16
18 20
96 51
20 6
10 3
1 1
0 0
Rini BI, et al. ASCO 2011. Abstract 4503. Reprinted with permission.

AXIS: PFS by Prognostic Factors and Baseline Characteristics

Authors: data support axitinib as the standard second-line therapy for advanced RCC Axitinib Sorafenib
Baseline Factor n Benefit Benefit
ECOG PS 1 ECOG PS 0 Sunitinib-containing regimen Bevacizumab-containing regimen Temsirolimus-containing regimen Cytokine-containing regimen White Nonwhite Male Female Age < 65 Age 65 MSKCC favorable MSKCC intermediate/poor Asia Europe North America Other region
327 396 389 59 24 251 547 176 523 200 476 247 306 417 152 357 186 28
0.0 1.0 2.0 HR (95% CI) 3.0
Rini BI, et al. ASCO 2011. Abstract 4503.

AXIS: Patient Reported Outcomes on QoL

Composite endpoint: time to deterioration (TTD)*
Survival Distribution Function 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 2 4 Median TTD, Mos Axitinib 3.1 Sorafenib 2.8 95% CI 2.8-4.5 2.7-3.0
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
P = .014 (HR: 0.829; 95% CI: 0.701-0.981)
Extending PFS in mRCC *Death, disease progression, or decrease in FKSI-15 scores. has QoL value
1-sided
6 8 10 12 14 16 18 20 22 24 Time to Composite (Mos)
P value.
Cella D, et al. ASCO 2011. Abstract 4504. Reprinted with permission.

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: 0.6380.859; P < .0001) Survival benefit seen regardless of baseline CTC level
AA + Prednisone (n = 649) 22.1 (20.4-24.1) 10.9 (9.9-12.0) Placebo + Prednisone (n = 323) 19.7 (16.7-NE) 8.2 (7.4-9.3)
Median OS, Mos (95% CI) Favorable CTC (< 5 cells/ 7.5 mL blood) Unfavorable CTC ( 5 cells/7.5 mL blood)
Higher CTC conversion rates (from 5 to < 5) with abiraterone

AA + Prednisone 42 Placebo + Prednisone 14 P Value <.0001
CTC Conversion, % Wk 4 (n = 422)
Wk 8 (n = 374)
Wk 12 (n = 330)
50
48
17
17
<.0001
<.0001
Scher HI, et al. ASCO 2011. Abstract LBA4517.

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)*
Treatment Fold change in LDH Baseline LDH CTC conversion 1.030 (0.773-1.372) 1.252 (1.047-1.497) 3.036 (2.276-4.048) 0.386 (0.284-0.527)
P Value*
.8371 .0135 < .0001 < .0001
Baseline CTC
*Adjusted for the biomarker panel.
1.135 (0.987-1.306)
.0747
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
70 60 50 40 30 20 10 0 155/349 (44.4%) 44/163 (27.0%) Pts Not Experiencing Palliation (%) 100 80 60 40 20 0 0 3 6 Mos 9 12 Median: 5.55 mos P = .0010 (log rank) AA Placebo Patients Experiencing Palliation (%)
Median: 10.25 mos
AA (n = 797)
Placebo (n = 398)
Pain Interference
Abiraterone + Prednisone (n = 797)
Placebo + Prednisone (n = 398)
P Value
Palliation, %
Median time to palliation, mos TTP (25th percentile), mos
59.2
1.02 9.27
38.0
3.71 4.57
.0004
.0009 .0019
Logothetis C, et al. ASCO 2011. Abstract 4520. Reprinted with permission.

COU-AA-301: Concluding Efficacy Results

Efficacy Measure Abiraterone + Prednisone (n = 797) 14.8 29.1 5.6 Placebo + Prednisone (n = 398) 10.9 5.5 3.6 P Value
Median OS, mos Confirmed PSA response, % Median radiographic PFS, mos
< .0001 < .0001 < .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
12 wks Patients with mCRPC, measurable disease, and mRECIST progression; rising PSA only, not eligible Randomization PR or CR (n = 79) Open-Label Extension Cabozantinib 100 mg/day PO Cabozantinib 100 mg/day PO (n = 14) Until PD*
Lead-in Stage Cabozantinib 100 mg/day PO (n = 171)
SD (n = 31)
Placebo daily (n = 17)
*At progression, patients on placebo could cross-over to cabozantinib (n = 14). Hussain M, et al. ASCO 2011. Abstract 4516.
PD (n = 61)
Discontinue Cabozantinib

Cabozantinib vs Placebo in mCRPC: Efficacy and Safety

1.00 Proportion Progression Free 0.75 HR 0.13; log-rank P value .0007 0.50
mPFS, Wks Cabozantinib (n = 14) 21 Placebo (n = 17) 6
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
0.25
-12 0 12-Wk Lead-in Stage
10
20 30 40 50 PFS per mRECIST, Post Randomization (Wks)
60
Hussain M, et al. ASCO 2011. Abstract 4516. Reprinted with permission.

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
275 250 225 200 175 150 125 100 75 50 25 0 -25 -50 -75 -100 -125
PSA Change at 12 Wks (%)
xx x
Xxx
x x
x x
Xx x
xx x
xxx
Treatment
300 mg BID (n = 23) 600 mg BID + prednisone (n = 26) X Previous ketoconazole therapy
400 mg BID + prednisone (n = 24) 600 mg QD AM (n = 24)
Agus DB, et al. ASCO 2011. Abstract 4531. Reprinted with permission.

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
70 60 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90
Best overall response:
PD
PR
SD
Outcome
Maximum Change From Baseline in Tumor Size (%)
All Patients (N = 50) 30.1 (12.1-66) 6.1 32 22
Dose Escalation to 350 mg No (n = 27) 27.1 (26.6-27.6) 5.9 (5.1-6.4) 22.2 14.8 Yes (n = 23) 30.4 (12.1-66.0) 11.1 (5.1-22.1) 43.5 30.4
Median response duration, wks (range) Median PFS, wks (range) 3-mo PFS, % 6-mo PFS, %
Stadler WM, et al. ASCO 2011. Abstract 4567. Reprinted with permission.

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

Outcome Median OS, mos (95% CI) Median PFS, mos (95% CI) PFS at 2 mos, % Patients (n = 37) 10.3 (7.8-16.1) 3.3 (2.1-3.7) 62
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

p-4E BP1 Expression by IHC 1+ (n = 12) 2+ (n = 23)
Outcome, n
PFS at 2 mos*
Progression at < 2 mos *P = .08 Milowsky MI, et al. ASCO 2011. Abstract 4606.
5
7
17
6
Thoracic Cancers

Status of Actionable Driver Mutations in Lung Adenocarcinoma Tumor Specimens

No mutation detected KRAS (22%) EGFR (17%) EML4-ALK (7%) Double mutants (3%) BRAF (2%) AKT1 NRAS MEK1 MET AMP HER2 PIK3CA
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.

EURTAC: Erlotinib vs Chemo in EGFR Mutation-Positive, Stage IIIB/IV NSCLC

Phase III; significant benefit in PFS and with erlotinib vs chemotherapy
1.0 PFS Probability 0.8 Erlotinib (n = 86) Chemotherapy (n = 87) HR: 0.37 (95% CI: 0.250.54; log-rank P < .0001)
0.6
0.4 0.2 0 0 3
5.2
9.7
12
Patients at Risk, n Erlotinib 86 63 Chemo 87 49
15 18 Mos
21
24
27
30
33
54 20
32 8
21 5
17 4
9 3
7 1
4 0
2 0
2 0
0 0
Rosell R, et al. ASCO 2011. Abstract 7503. Reprinted with permission.

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
All < 65 yrs 65 yrs Male Female PS 0 PS 1 PS 2 Current smoker Former smoker Never smoker Exon 19 deletion L858R mutation
0.1 0.2 0.4 0.6 0.81.0 1.5 2.0 4.0
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)
n 173 85 88 47 126 57 92 24 19 34 120 115 58
Favors Erlotinib HR Favors Chemotherapy Rosell R, et al. ASCO 2011. Abstract 7503.

EURTAC: Response and Safety

Response Outcome, % Objective response CR PR Erlotinib (n = 86) 58 2 56 Chemo (n = 87) 15 0 15
CT-treated patients had increased frequency of:

Grade 3/4 AEs (81% vs 45%) Dose modification or interruption due to treatmentrelated AE (47% vs 23%) Discontinuation due to treatment-related AE (14% vs 5%) Treatment-related serious AEs (16% vs 7%)
Disease control rate

SD PD No response assessed
79
21 7 14
66
51 13 22
Rosell R, et al. ASCO 2011. Abstract 7503.

PARAMOUNT: Maintenance Pem Following Induction With Pem/Platinum

Double-blind phase III trial
Previously untreated advanced-stage nonsquamous NSCLC Pemetrexed 500 mg/m2 + Cisplatin 75 mg/m2 both administered on Day 1 of a 21-day cycle (n = 939) Pemetrexed 500 mg/m2 on Day 1 of a 21-day cycle + BSC (n = 359)
CR, PR, Both arms received folic acid and vitamin B12 therapy or SD
PD
Induction phase (4 cycles)
21-42 days
Placebo on Day 1 of a 21-day cycle + BSC (n = 180)

Maintenance phase (until PD)
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)
Paz-Ares LG, et al. ASCO 2011. Abstract CRA7510.

PARAMOUNT: Efficacy, Safety, and QoL

1.0 PFS From Randomization 0.8 mPFS, Mos Pem + BSC 4.1 Placebo + BSC 2.8 Unadjusted HR: 0.62 (95% CI: 0.49-0.79; log-rank P = .00006)
Improved disease control rate with pemetrexed vs placebo maintenance

71.8% vs 59.6%, respectively (P = .009)
0.6
0.4 0.2 0.0 0 3

132 52
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)
6 Mos
57 15
9
21 5
12
4 0
15
0 0
Pts at Risk, n Pem + BSC 359 Placebo + BSC 180
No significant difference in healthrelated 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

HGF HGF
MetMAb: monovalent antibody to Met

Prevents Met activation by hepatocyte growth factor
MetMAb
EGFR mutations in study population

Met diagnostic-positive population: imbalanced on MetMAb arm Met diagnostic-negative population: imbalanced on placebo arm
Met
Met
Growth Migration Survival No activity
Predefined Met diagnostic-positive population

Tumor samples with 50% tumor cells displaying moderate or strong Met staining by IHC
Spigel DR, et al. ASCO 2011. Abstract 7505. Reprinted with permission.

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 ITT Population (n = 137) MetMAb + Erlotinib (n = 69) Median PFS, mos HR (95% CI) P value Median OS, mos HR (95% CI) P value 8.9 .34 2.2 .69 7.4 12.6 .002 0.80 (0.50-1.28) Placebo + Erlotinib (n = 68) 2.6 Met DiagnosticPositive Population (n = 66) MetMAb + Erlotinib (n = 35) 2.9 .04 3.8 8.1 .16 0.37 (0.19-0.72) Placebo + Erlotinib (n = 31) 1.5 Met DiagnosticNegative Population (n = 62) MetMAb + Erlotinib (n = 31) 1.4 .05 15.3 1.78 (0.79-3.99) Placebo + Erlotinib (n = 31) 2.7
1.09 (0.73-1.62)
0.53 (0.28-0.99)
1.82 (0.99-3.32)
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) 2.7 1.71 (0.96-3.02) .06 3.8 2.61 (1.34-5.09) .004 15.3
Median PFS, mos HR (95% CI) P value Median OS, mos HR (95% CI) P value
Spigel DR, et al. ASCO 2011. Abstract 7505.
1.5

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

1-yr OS, % 2-yr OS, % HR vs ALK/control P value HR vs WT/control P value
Shaw AT, et al. ASCO 2011. Abstract 7507.
NR
70 55 0.36 .004 0.49 .02
6
44 12
11
47 32
1.42 .18

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

Platinum sensitive Platinum refractory Median PFS, mos
Jotte R, et al. ASCO 2011. Abstract 7000.
7.5
9.2 6.2 4.1
7.8
9.9 5.7 3.5
0.880 (0.733-1.057)
0.936 (0.724-1.211) 0.766 (0.589-0.997) 0.802 (0.667-0.965)
.1701
.6164 .0469 .0182

RTOG 0522: Frontline Cisplatin/RT Cetuximab in Stage III/IV HNSCC

Randomized phase III trial
100 80 Survival (%) 60 40 20 0 2-Yr PFS 2-Yr OS
Ang KK, et al. ASCO 2011. Abstract 5500.
Cetuximab + cisplatin/RT Cisplatin/RT 82.6 79.7 63.4 64.3
No statistical difference in 2-yr PFS (primary endpoint) or 2-yr OS between treatment arms
PFSHR: 1.05 (95% CI: 0.84-1.29; P = .66) OSHR: 0.87 (95% CI: 0.66-1.15; P = .17)

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

Cetuximab + cisplatin/RT Cisplatin/RT 100 80 Rate (%) 60 40
Risk of distant metastasis at 2 yrsHR: 0.74 (95% CI: 0.49-1.11; P = .07)

Local-regional progression at 2 yrsHR: 1.21 (95% CI: 0.92-1.60; P = .92)
24.5
20 0
19.8 7.6
Grade 3/4 skin reactions and mucositis with cetuximab

12.0
Late toxicity similar between arms

Survival similar by p16 gene expression
2-Yr Locoregional Progression
2-Yr Distant Metastasis
Ang KK, et al. ASCO 2011. Abstract 5500.

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 HPVnegative 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)
Pathologic Response, % pCR* pCR* + npCR All 28 53 ER Positive 21 56 ER Negative 40 48
*pCR defined as no invasive cancer in breast. npCR defined as < 1 cm residual disease in breast.
Chang JCN, et al. ASCO 2011. Abstract 505.

TBCRC 006 vs Other Neoadjuvant Trials in HER2-Positive Disease

Study and Treatment TBCRC 006[1] Lapatinib + trastuzumab for 12 wks NeoALTTO[2] Lapatinib 18 wks with paclitaxel added for last 12 wks Trastuzumab 18 wks with paclitaxel added for last 12 wks Lapatinib + trastuzumab 18 wks with paclitaxel added for last 12 wks NeoSphere[3] Trastuzumab + docetaxel for 12 wks Pertuzumab + docetaxel for 12 wks Trastuzumab + pertuzumab + docetaxel for 12 wks Trastuzumab + pertuzumab for 12 wks Geparquinto (GBG 44)[4] Lapatinib + epirubicin/cyclophosphamide docetaxel for 24 wks Trastuzumab + epirubicin/cyclophosphamide docetaxel for 24 wks
*No invasive cancer in breast. 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.
Pts, n 66 455 154 149 152
pCR,* % 28
24.7 29.5 51.3 29.0 24.0 45.8 16.8

35.2 50.4
107 96 107 107

615 308 307

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: 0.180.70; P = .002)
Goss PE, et al. ASCO 2011. Abstract LBA504. Goss, PE, et al. N Engl J Med. 2011;364:2381-2391.
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

NCIC CTG MAP.3: Safety

No increase in incidence of SAEs with exemestane over 3 yrs, including fractures, osteoporosis, CV toxicity, or second malignancies
Adverse Event (All Grades), % Hot flashes Joint pain Fatigue Vaginal dryness Arthritis Depression Insomnia Muscle pain Nausea Diarrhea Exemestane (n = 2240) 40 30 23 16 11 11 10 7 7 5 Placebo (n = 2248) 32 27 21 15 9 10 8 9 5 3 P Value < .0001 .04 .03 .68 .01 .96 .04 .01 .04 .002
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].

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 Paclitaxel 175 mg/m +
2
Pegfilgrastim q2w for 6 cycles 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) Paclitaxel 80 mg/m2/wk for 12 cycles
AC + G (n = 1341)
Paclitaxel 175 mg/m2 + Pegfilgrastim q2w for 6 cycles Paclitaxel 80 mg/m2/wk for 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. Budd GT, et al. ASCO 2011. Abstract 1004.

SWOG S0221: DFS

Primary endpoint: DFS
1.00
0.75
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
0.50
5-Yr DFS, % AC q2w (n = 1342; 183 events) 82 AC + G (n=1320; 202 events) 79 HR = 1.15 (95% CI: 0.95-1.41) P = .16
DFS
0.25
0 0 2 4 6 Yrs Since Registration
Study still ongoing to assess whether weekly paclitaxel superior to q2w 8 paclitaxel
Budd GT, et al. ASCO 2011. Abstract 1004. Reprinted with permission.

SWOG S0221: Safety

Toxicity profiles of AC + G vs AC q2w differed
AC + G
5.25 15.0 23.0 3.4 2.0 2.7 0.4 0.5 8.2 17.0
Grade 3/4 Adverse Event During AC Segments, %

Anemia Leukopenia Neutropenia Thrombocytopenia Infection Febrile neutropenia Nonneutropenic Cardiotoxicity During AC segments During AC and paclitaxel segments Mucositis Dermatologic/hand-foot syndrome
Budd GT, et al. ASCO 2011. Abstract 1004.
AC q2w
9.6 20.0 26.0 2.8 6.0 2.9 1.1 2.2 2.0 2.0
P Value
< .001 .001 .09 .6 < .001 .84 .046 < .001 < .001 < .001

Phase III: Addition of Iniparib (BSI-201) to Gemcitabine/Carboplatin in mTNBC

Coprimary endpoints: OS and PFS
1.0 0.8 PFS Probability 0.6 0.4 0.2 0 0 Outcome, Mos Median PFS Median OS 2 4 6 8 10 Mos 12 14 16 GC (n = 258) 4.1 11.1 OS Probability 1.0 0.8 0.6 0.4 0.2 0 0 2 4 6 8 10 Mos 12 14 16 P Value .027 .28
GCI (n = 261) 5.1 11.8
HR (95% CI) 0.79 (0.65-0.98) 0.88 (0.69-1.12)
OShaughnessy J, et al. ASCO 2011. Abstract 1007. Reprinted with permission.

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. OShaughnessy J, et al. ASCO 2011. Abstract 1007. 2. OShaughnessy 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
100 80 PFS (%) 60 40 20 0 15 20 Mos Dieras V, et al. ASCO 2011. Abstract 544. Reprinted with permission. 0 5 10 25 30 mPFS, Mos AMG 386 10 mg/kg qw + P + Bev (n = 56) 11.3 AMG 386 3 mg/kg qw + P + Bev (n = 57) 9.2 Placebo qw + P + Bev (n = 58) 12.2 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 + Paclitaxel + Bevacizumab for First-line Tx of HER2-Negative Advanced BC

100 2 7.3 4.3 CR 80 49 Patients (%) 60 cORR: 51% 63.4 cORR: 70.7% 59.5 cORR: 41.3 59.5% cORR: 45.7% PR SD PD NE/NA 40 26.5 30.4
20
31
10.2 12.2 2.4 2.4 24.4 4.8 4.8 13 10.9
AMG 386 3 mg/kg
AMG 386 10 mg/kg
Placebo
Open-Label AMG386 10 mg/kg + Paclitaxel
+ Paclitaxel + Bevacizumab Dieras V, et al. ASCO 2011. Abstract 544.
Gastrointestinal Cancer

Panitumumab + Rilotumumab or Ganitumab for mCRC With WT KRAS

Rilotumumab: fully human HGF mAb Phase Ib: DLT assessed Phase II: randomized comparison
Panitumumab + Rilotumumab* (n = 48) 31 0 31
Primary endpoint: ORR Probability that combination better than panitumumab alone
Panitumumab + rilotumumab: 93%
Ganitumab: fully human IGF-1R mAb
Panitumumab + ganitumab: 63%

Panitumumab + Ganitumab* (n = 46) 22 0 22 Panitumumab + Placebo* (n = 48) 21 0 21
Response, %
ORR CR PR
SD PD
40 23
39 33
35 33
*Panitumumab dosed at 6 mg/kg, rilotumumab dosed at 10 mg/kg, and ganitumab dosed at 12 mg/kg; all doses administered q2w. Eng C, et al. ASCO 2011. Abstract 3500.

Panitumumab + Rilotumumab or Ganitumab: Adverse Events

Grade 3/4 Adverse Event,* % Any Rash Acneiform dermatitis Hypomagnesemia Abdominal pain Panitumumab + Rilotumumab (n = 48) 71 29 15 4 4 Panitumumab + Ganitumab (n = 46) 63 13 11 15 7 Panitumumab + Placebo (n = 48) 52 8 10 2 6
Anemia
Constipation Acne Asthenia Diarrhea Fatigue Paronychia Skin toxicity Eng C, et al. ASCO 2011. Abstract 3500.
0
0 4 0 4 4 4 2
0
0 0 4 2 2 2 4
8
6 0 0 0 2 2 0
*Occurring in > 2% of patients in any treatment arm.

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 or OR* in Pooled Analysis (95% CI) Median PFS Median OS KRAS WT 0.66 (0.55-0.80) 0.81 (0.69-0.94) KRAS G13D 0.60 (0.32-1.12) 0.80 (0.49-1.30) KRAS G12V 1.55 (0.94-2.56) 1.10 (0.75-1.62) KRAS Other Muts 1.37 (1.02-1.84) 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)
*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.

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
5-FU vs capecitabine
Outcome, % pCR SD 5-FU 18.8 20.7 Capecitabine 22.2 23.0 P Value .12 .62
SSS
61.2
62.7
.59
Oxaliplatin vs no oxaliplatin
More grade 3/4 diarrhea with oxaliplatin vs no oxaliplatin: 15.4% vs 6.6% (P = .0001)
Outcome, % pCR SD SSS No Oxaliplatin 19.1 23.0 63.6 Oxaliplatin 20.9 19.2 60.4 P Value .46 .48 .28
All pts received neoadjuvant radiation in addition to CT Primary endpoint: locoregional relapse rate (data not yet mature)
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

1.0 PFS Probability 0.8 0.6 0.4 0.2 74% 60% XELOX (n = 520) Observation (n = 515)
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%
0
0
HR: 0.56 (95% CI: 0.44-0.72; P < .0001)

6 12 18 24 30 Mos 36 42 30 22 48 10 6
No. left XELOX 520 443 410 333 246 166 74 Observation 515 414 352 286 209 147 58
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.

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, % Nausea Neutropenia Peripheral neuropathy Diarrhea 66 60 56 47 XELOX (n = 496) All Grades Grade 3/4 8 22 2 2
Vomiting
Thrombocytopenia Hand-foot syndrome Stomatitis Cardiac disorders
Bang Y, et al. ASCO 2011. Abstract LBA4002.
39
26 19 12 2
7
8 1 <1 <1

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
Median f/u: 17 mos (95% CI: 16-18 mos) Median 95% CI SLC + BSC 5.1 mos 4.0-6.2 BSC alone 3.8 mos 3.0-4.6
1.0 OS Probability 0.8 0.6 0.4 0.2 0 0
Log rank P = .009
6 Mos
12
18
Park SH, et al. ASCO 2011. Abstract 4004. Reprinted with permission.

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
Grade 3/4 AE, % SLC + BSC Docetaxel (n = 66) Fatigue Anorexia Nausea Diarrhea Stomatitis
Park SH, et al. ASCO 2011. Abstract 4004.
Irinotecan (n = 60) 20 5 3 8 2
BSC Alone (n = 62) 27 10 6 5 2
17 6 5 3 6
Hematologic Malignancies

COMFORT-II (Phase III): Ruxolitinib in Myelofibrosis

Ruxolitinib (INCB18424): potent and selective JAK1/2 inhibitor
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*
Primary endpoint: 35% reduction in spleen volume by MRI at Wk 48

35% Reduction in Spleen Volume, % (95% CI) Wk 24 Wk 48 Ruxolitinib (n = 146) 31.9 (24.4-40.2) 28.5 (21.3-36.6) BAT (n = 73) 0 (0-5) 0 (0-5) P Value < .0001 < .0001
*Progression defined as splenectomy or 25% spleen volume increase from baseline or on-study nadir. Harrison CN, et al. ASCO 2011. Abstract LBA6501.

COMFORT-II: Survival and QoL

Mean Change in EORTC QLQ-C30 Scores From Baseline to Wk 48 Global health status or QoL Ruxolitinib (n = 69) 9.1 (n = 66) BAT (n = 28) 3.4 (n = 27)
Role functioning
Select symptoms common to myelofibrosis Loss of appetite Insomnia Dyspnea
9.9
-5.4
-8.2 -12.3 (n = 68) -6.3
9.5 6.0 4.8
Pain
-1.9
3.0
Fatigue -12.8 0.4 PFS, LFS, and OS did not significantly improve with ruxolitinib treatment Ruxolitinib associated with improvement in symptoms and functioning
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) 38 47 35 Cytarabine Alone (n = 157) 17 23 18 P Value
4-mo EFS ORR CR
< .0001 < .0001 .0005
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)
Faderl S, et al. ASCO 2011. Abstract 6503.

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
Response, % Decitabine (n = 242) 17.8* Treatment Choice (n = 243) 7.8* Low-Dose Cytarabine (n = 215) 8.4 Supportive Care (n = 28) 3.6
CR + CR with incomplete platelet recovery *P = .001; OR: 2.5 (95% CI 1.40-4.78).
> 50% of pts with treatment-related grade 3/4 adverse event; rates similar between decitabine and cytarabine treatment (low with SC)
Thomas XG, et al. ASCO 2011. Abstract 6504.

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
Outcome, % CHOP R for 1 Cycle + ASCT (n = 125) 69 74 CHOP R for 3 Cycles (n = 128) 56 71 HR (95% CI) P Value .005 .16
2-yr PFS 2-yr OS
1.72 (1.18-2.51) 1.24 (0.81-1.91)
Higher incidence of grade 3/4 adverse events observed with ASCT ASCT significantly prolonged PFS in patients with advanced highintermediate 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
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-CHOEP-14 x 8 Cycles (n = 130) 69.5 75.5 73.7 84.6 91.0 R-MegaCHOEP + ASCT x 4 Cycles (n = 132) 61.4 63.5 69.8 77.0 77.1 .081 .013 P Value
Outcome at Yr 3, %
EFS aaIPI 2 PFS OS aaIPI 2
.140 .051
R-MegaCHOEP followed by ASCT not superior R-CHOEP-14
Schmitz N, et al. ASCO 2011. Abstract 8002.

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

Stratified by center and age-adjusted IPI
4 cycles; evaluation
PET neg
R-CHOP-14 4 cycles
Adults (60 yrs of age or younger) with DLBCL (N = 312)
CHOP-14 + Rituximab 375 mg/m2 on Day 1 (n = 156) HDT + Rituximab 375 mg/m2 on Day 1 (n = 156)
PET pos
R-DHAP x 3 BEAM
PET neg
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
3-Yr Survival, % EFS Age-adjusted IPI 0-1 CHOP-14 + Rituximab (n = 156) 56 57 HDT + Rituximab (n = 156) 41 46 P Value .03 .3
Age-adjusted IPI 2-3

PFS OS (median not reached)
56
81 85
37
79 82
.06
.9 NS
Authors conclude that R-CHOP-14 for 8 cycles could become new standard in patients who are PET negative after 4 cycles
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%, respectively
Gisselbrecht 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
Survival After Maintenance Therapy, Mos Median EFS Median PFS Maintenance Rituximab (n = 122) 57.6 57.6 No Additional Therapy (n = 120) 58.2 58.2 P Value
.7435 .8314
Median, mos
Not reached
62.9
.7547
Median PFS longer for females vs males in rituximab maintenance arm

Not reached vs 25.3 mos (P = .0044)
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
Risk for PD or death greater than risk for SPM in each treatment arm
Total invasive SPMs 10 Incidence of SPMs (%) 8 6 4.7 4 2 0.7 0 MPR-R MPR MP 3.3 3.3 2.6 2.6 2.0 8.0 5.9 Hematologic malignancies Solid tumors
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
Palumbo AP, et al. ASCO 2011. Abstract 8007.

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-yrs
Rossi 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

Proposed Model for SPM Following MM
Treatment of MM
Potential bias in evaluating SPM

Reporting of SPM varies between treatment arms Often survival differences between treatment arms Differences in study design
Behavioral factors
Second malignancy
MM related factors
Mechanism of SPM in MM currently unknown

Host related factors Environmental factors
Clinicians should weigh the demonstrated benefits of therapy with the risk of SPM
Landgren O. ASCO 2011. Discussant. Reprinted with permission.
Sarcomas

SUCCEED: Ridaforolimus Maintenance in Patients With Metastatic Sarcoma

Double-blind phase III trial Ridaforolimus: oral rapamycin analogue with potent activity against mTOR
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
Patients with metastatic sarcoma who had attained CR, PR, or SD from previous standard chemotherapy (N = 711)
Primary endpoint (PFS) significantly prolonged vs placebo

Ridaforolimus (n = 347)
17.7 70 34
Outcome, IRC Assessment

Median PFS, wks PFS rate, % 3 mos 6 mos
Placebo (n = 364)
14.6 54 23
HR
0.72
P Value
.0001
Chawla SP, et al. ASCO 2011. Abstract 10005.

SUCCEED: OS, Response, and Safety

Clinical benefit (CR + PR + SD 4 mos) significantly improved
Outcome
Median OS, mos
Ridaforolimus (n = 347)
21.4
Placebo (n = 364)
19.2
HR
0.88
P Value
.2256
Clinical benefit, %
Best target lesion response, mean tumor size %
40.6
-1.3
28.6
+10.3
---
.0009
< .0001
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
Chawla SP, et al. ASCO 2011. Abstract 10005.
Ovarian Cancer

OCEANS: Bev + Carboplatin/Gemcitabine in Recurrent Ovarian Cancer

Platinum-sensitive recurrent OC* Measurable disease ECOG 0/1 No previous chemo for recurrent OC No previous Bev
(n = 484)
CG + PL
C AUC 4 G 1000 mg/m2 Days 1 & 8 PL q3w until progression C AUC 4
CG + Bev
G 1000 mg/m2 Days 1 & 8 Bev 15 mg/kg q3w until progression CG for 6 (up to 10) cycles
*Epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Population
Median PFS, Mos

Bev + CG (n = 242) Placebo + CG (n = 242) 8.4 8.6
HR (95% CI)
P Value
Investigator assessed IRC assessed
12.4 12.3
0.484 (0.388-0.605) 0.451 (0.351-0.580)
< .0001 < .0001
Aghajanian C, et al. ASCO 2011. Abstract LBA5007.

OCEANS: OS, Response, and Safety

In interim analysis, trend toward improved OS; final OS results awaited
Outcome Objective response, % CR PR Median duration of response, mos Bev + CG (n = 242) 78.5 17 61 10.4 Placebo + CG (n = 242) 57.4 9 48 7.4 0.534 (0.408-0.698) < .0001 HR (95% CI) -P Value < .0001
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.
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 Conference Highlights reviewing the potential impact of these new findings on clinical practice

CCO ClinOncJune2011 Highlights Slides 1

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CCO ClinOncJune2011 Highlights Slides 1

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Highlights From the 2011 Clinical Oncology Meeting

CCO Independent Conference Coverage

Clinical Oncology 2011

About These Slides

Clinical Oncology 2011

Clinical Oncology 2011

Robert M. Rifkin, MD, FACP

Clinical Oncology 2011

Clinical Oncology 2011

Clinical Oncology 2011

Overview of Tumor Types Covered in This Slideset

Clinical Oncology 2011

BRIM3: Vemurafenib vs Dacarbazine in BRAF V600EPositive Melanoma

Outcome Estimated 6-mo OS, % Median PFS, mos ORR, % CR

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

Clinical Oncology 2011

Clinical Oncology 2011

MDX-024: Ipilimumab + Dacarbazine vs Dacarbazine in Unresectable Melanoma

Yr 1 Yr 2 Wolchok JD, et al. ASCO 2011. Abstract LBA5.

Clinical Oncology 2011

MDX-024: Median OS, PFS, and Response

0.72 (0.59-0.87) 0.76 (0.63-0.93)

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

Clinical Oncology 2011

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

Clinical Oncology 2011

EORTC 18991: Long-term PegIFN alfa-2b in Stage III Melanoma

Most common AEs did not worsen as treatment duration increased

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

Clinical Oncology 2011

BRAF Inhibitor (GSK436) + MEK Inhibitor (GSK212) in BRAF-Mutated Melanoma

Clinical benefit (CR + PR + SD)

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

Clinical Oncology 2011

Treatments generally well tolerated; similar toxicity

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

Clinical Oncology 2011

AXIS: PFS by Prognostic Factors and Baseline Characteristics

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

Clinical Oncology 2011

AXIS: Patient Reported Outcomes on QoL

P = .014 (HR: 0.829; 95% CI: 0.701-0.981)

6 8 10 12 14 16 18 20 22 24 Time to Composite (Mos)

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

Clinical Oncology 2011

COU-AA-301: Final Analysis, Evaluation of CTCs as Efficacy-Response Biomarker

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

CTC Conversion, % Wk 4 (n = 422)

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

Clinical Oncology 2011

Efficacy-Response Biomarker Panel, Potential Surrogate for OS in mCRPC

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

Clinical Oncology 2011

COU-AA-301: Effect of Abiraterone Acetate on Pain Palliation and SREs

Median: 10.25 mos

Abiraterone + Prednisone (n = 797)

Placebo + Prednisone (n = 398)

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

Clinical Oncology 2011

COU-AA-301: Concluding Efficacy Results

< .0001 < .0001 < .0001

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

Clinical Oncology 2011