2012 gu cancers symposium
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2012 GU Cancers Symposium. San Francisco, CA February 2-4, 2012. Jerry M. Maniate MD, M.Ed, FRCPC Assistant Professor, Department of Medicine University of Toronto Dr. H. James Watt Hematology/Oncology Clinic Service of Hematology/Oncology Director of Medical Education

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2012 GU Cancers Symposium

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2012 gu cancers symposium

2012 GU Cancers Symposium

  • San Francisco, CA

  • February 2-4, 2012

Jerry M. Maniate MD, M.Ed, FRCPC

Assistant Professor, Department of Medicine

University of Toronto

Dr. H. James Watt Hematology/Oncology Clinic

Service of Hematology/Oncology

Director of Medical Education

St. Joseph’s Health Centre


Objectives

Objectives

  • In the next 30 minutes...


Outline

Outline

  • Prostate Cancer

  • Bone Targeted Therapy

  • Renal Cell Cancer


Highlights of guca symposium

Highlights of GUCA Symposium

  • 2500 attendees

  • 284 Prostate cancer abstracts

  • 136 Renal cell carcinoma abstracts


Novel targets novel agents

Novel Targets & Novel Agents


Mdv3100

MDV3100

  • Specific inhibitor of androgen receptor

  • No known effect on androgen production

  • Preclinical: anti-proliferative activity on prostate cancer cells that harbour amplification of AR

Scher, Lancet 2010; 375: 1437

Scher, JCO, March 1, 2006


Mdv31001

MDV3100

  • Progression measured as rising PSA

  • Improved OS post-docetaxel

  • Median OS: 18.4 mths vs.

  • Not hormone resistant but rather castrate resistant due to drive of AR signaling

Scher, Lancet 2010; 375: 1437

Scher, JCO, March 1, 2006


2012 gu cancers symposium

Post-chemotherapy: failed docetaxel

MDV3100

160 mg po OD

Placebo

Primary EP:

Overall Survival

Secondary EP:

Radiographic PFS

Time to first SRE

Time to PSA progression

Circulating tumour cell count conversion rate

AFFIRM Study. Scher HI et al. JCO 30, 2012 (suppl 5; abstract LBA1)


Affirm study

AFFIRM Study

  • N = 1199 pts (800 vs. 399)

  • Balanced demographics / disease characteristics

  • 520 death events reached

  • Independent Drug Monitoring Committee (IDMC) concluded that the trial be stopped, unblinded and that the patients on placebo be offered the test agent


2012 gu cancers symposium

Post-chemotherapy: failed docetaxel

MDV3100

160 mg po OD

Placebo

18.4 mths

13.6 mths

p<0.001

Median OS

PFS

Time to PSA progression

Safety

TO FOLLOW

AFFIRM Study. Scher HI et al. JCO 30, 2012 (suppl 5; abstract LBA1)


Affirm study1

AFFIRM Study

  • Survival benefit observed across subgroups vs. placebo

  • Median duration of Tx: 8.3 vs. 3.0 mths

  • Tumour response on imaging

  • No difference in adverse events

  • No myelosuppression

  • 0.6% had seizures (5 pts: 2 with brain mets, 2 had lidocaine for biopsies)


Prevail study

PREVAIL Study

  • Asymptomatic or minimally symptomatic men with metastatic PrCa who are chemotherapy naive


Bone targeted therapy

Bone Targeted Therapy


Radium 223 chloride

Radium-223 Chloride

  • ALSYMPCA Study


Alsympca study

ALSYMPCA Study

  • Radium-223 acts as a calcium mimic

  • Integrated into bone

  • Alpha emitter that provides localized effect

  • Induces dsDNA breaks in adjacent tumour cells

  • Short penetration

  • Phase 2: Nilsson, Lancet Onco

GUCA 2012, Abstract 8


Alsympca study1

ALSYMPCA Study

  • Phase 3: post-docetaxel and docetaxel ineligible

  • BSC ± Radium-223

  • 6 injections at 4-wk intervals

  • N = 541 (radium) vs. 268 (placebo)

  • No cytotoxic chemotherapy

  • Primary EP: OS

  • Secondary EP: QoL, safety


Alsympca study2

ALSYMPCA Study

  • Planned interim analysis at 320 deaths

  • Balanced baseline characteristics

  • Results:

    • OS: 14.0 mths vs. 11 mths (stat sig)

    • No routine imaging unlike DEN & Zometa studies


Alsympca study3

ALSYMPCA Study

  • SRE: include spinal cord compression, pathologic fractures

    • Reduced risk for SCC with Radium-223 vs. placebo

  • A/E:

    • Modest increase in neutropenia but only 2%

    • Very well tolerated


Bone protection in metcrpc

Bone Protection in MetCRPC

  • Can we prolong bone metastases free survival?

  • Fracture prevention?

  • Should we place patients on bone protective agent?

    • Zoledronate vs. Denosumab?

  • What is the optimal scheduling?

  • Individualization of options?


Bone protection in metcrpc1

Bone Protection in MetCRPC

  • Considerations for individualization:

    • Poor dentition

    • Convenience: IV vs. SC

    • Renal dysfunction

    • Side effects

    • Cost and co-payments

    • Are these agents necessary when other agents are being used?


Renal cell carcinoma

Renal Cell Carcinoma


Rcc in the vulnerable patient

RCC in the Vulnerable Patient

  • Comorbidity Scores


Rcc comorbidity scores

RCC & Comorbidity Scores

  • Accounting for comorbidities is important for clinical prognosis

  • SEER Registry (1995- 2007 data)

    • 1155 people with T1a N0 M0, well-differentiated

    • At 10 years:

      • 4% mortality for RCC causes

      • 51% from non-RCC causes


Competing risks

Competing Risks

  • What diseases did the patient have before the cancer diagnosis?

  • Which ones are relevant?


Charlson comorbidity index

Charlson Comorbidity Index

  • Developed by fitting a statistical model to evaluate predictors of mortality


2012 gu cancers symposium

  • Developed by fitting a statistical model to evaluate predictors of mortality

  • As CCI score increases, the mortality rate increases


Charlson comorbidity index1

Charlson Comorbidity Index

  • 203 older pts with cancer

    • Little or no correlation between comorbidty (CCI or Cumulative Illness Rating Scale - Geriatrics) and functional status (ECOG or ADLs)

  • An assessment of comorbid medical conditions can provide information that is independent of patient’s functional status. Thus need to assess both.

J Clin Oncol. 1998;16(4):1582


Charlson comorbidity index2

Charlson Comorbidity Index

  • CAUTIONS:

    • **Other measures may be more appropriate

    • Nomograms are statistical models that can be used to predict outcomes, and are visual representations of the model

    • Be careful of extrapolation to unusual values


Metastatic rcc

Metastatic RCC

  • When to treat?

  • What are the deciding factors for when to start systemic therapy?


Metastatic rcc goal

Metastatic RCC: Goal

  • Delay as long as possible a patient from reaching a lethal tumour burden while maintaining QoL

  • RCC is an inherently diverse disease with a diverse biology


Who can we observe

Who can we observe?

  • Good performance status

  • Low volume

  • Slow growing

  • Asymptomatic


When should we start

When should we start?

  • Increased pace of disease

  • New organ sites

  • Symptoms from disease

  • MD / patient anxiety


Therapy in mrcc

Therapy in mRCC

  • Advantages:

    • Reduction in tumour burden

    • Delay worsening of disease

    • Relatively convenient, oral therapy

  • Disadvantages:

    • Chronic therapy

    • Chronic toxicity


Sunitinib in elderly pts with mrcc

Sunitinib in Elderly Pts with mRCC

  • Pooled data analysis of 1059 pts

    • 65% (689 pts): Sunitinib 50 mg/d (4wks on, 2wks off)

    • 35% (370 pts): continuous OD dosing

    • 1st line setting: 74% (783 pts)

    • 2nd line setting: 26% (276 pts)

Hutson TE et al. J Clin Oncol. 29: 2011 (suppl; abstract 4604)


Sunitinib in elderly pts with mrcc1

Sunitinib in Elderly Pts with mRCC

  • Median PFS: 9.0 vs. 10.9 mths (p=0.0830)

  • Median OS: 23.3 vs. 23.7 mths (p=0.5441)

  • No difference when age taken

  • Overall tolerability is similar

  • In younger pts: increased HFS, chest pain

Hutson TE et al. J Clin Oncol. 29: 2011 (suppl; abstract 4604)


Ph 3 axis trial for mrcc

Ph.3 AXIS Trial for mRCC

  • What is the effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy?

  • Axitinib: potent and selective 2nd-gen VEGFR-I (VEGFR-1, -2, and -3)

Rini BI et al. GUCA Symp 2012; abstract 354


Axitinib

Axitinib

  • Potent and selective second-generation inhibitor of VEGFR-1, -2, and -3

  • If no toxicity > grade 2 and BP <150/90 mmHg without anti-HTN meds for >2 wks ➜ increase axitinib to 7mg po BID and then to 10 mg po BID

Rini BI et al. GUCA Symp 2012; abstract 354


Axis trial

AXIS Trial

Second Line mRCC (clear cell)

Axitinib

5 mg po BID

Sorafenib

400 mg po BID

6.7 mths

4.7 mths

Median PFS

p<0.0001

6.6 mths

At least one total daily dose > 10mg

N =132 pts

8.3 mths

At least one total daily dose ≤ 10mg

N = 227 pts

Rini BI et al. GUCA Symp 2012; abstract 354


Axis trial1

AXIS Trial

Second Line mRCC (clear cell)

Axitinib

5 mg po BID

Sorafenib

400 mg po BID

6.7 mths

4.7 mths

Median PFS

p<0.0001

N =194 pts (53.7%)

N =195 pts (53.9%)

Prior Sunitinib ≥9mths

6.3 mths

Prior Sunitinib <9mths

4.5 mths

Rini BI et al. GUCA Symp 2012; abstract 354


Foretinib

Foretinib

  • Oral multi-kinase inhibitor targeting MET, VEGF, RON, AXL and TIE-2 receptors

  • Activating mutations and/or amplifications in MET in papillary RCC

Choueiri TK et al. GUCA Symp 2012; abstract 355


2012 gu cancers symposium

Locally adv. or met papillary RCC

Intermittent arm

Foretinib

240 mg/d on day 1-5 of every 14 days

37 pts

Daily dose arm

Foretinib

80 mg/d

37 pts

ORR 13.5%

PFS 9.3 mths

1-yr OS 70%

Median OS not reached

Choueiri TK et al. GUCA Symp 2012; abstract 355


2012 gu cancers symposium

Locally adv. or met papillary RCC

Intermittent arm

Foretinib

240 mg/d on day 1-5 of every 14 days

37 pts

Daily dose arm

Foretinib

80 mg/d

37 pts

ORR 13.5%

PFS 9.3 mths

1-yr OS 70%

Median OS not reached

Choueiri TK et al. GUCA Symp 2012; abstract 355


Foretinib toxicity

Foretinib: Toxicity

  • Grade 3/4:

    • Fatigue 6.8%

    • HTN 50%

    • Diarrhea 6.8%

  • Non-fatal pulmonary embolism: 11%

  • No sig diff between the 2 cohorts in efficacy or safety


Summary

Summary

  • Prostate Cancer

  • Bone Targeted Therapy

  • Renal Cell Cancer


Questions

Questions

  • [email protected]


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