Geriatric Oncology – Why?

Andrew E. Chapman, DO FACP

March 10, 2016

Geriatric Oncology

-No Disclosures

Geriatric Oncology

Agenda

1) Rationale

2) Challenges Faced

3) Practice Changing Developments in Geriatric Oncology

4) Geriatric Oncology “To Do List”

5) Development/Function of a University Center

Chronologic Age does not equal Physiologic Age

Geriatric Oncology

Demographics

• Leading cause death men/women age 60-79

• 60% cancers in US patients are 65 and older

• 80% cancer-related deaths in US are 65 and older

• 20% of US population over age 65 by 2030

• 70% of all cancers

• 85% of all cancer related deaths

• Older individuals more prone to cancer

• Behavior of certain cancers change with age

• Future: increase in incidence of cancer/life expectancy

SEER Data Base, NCCN Guidelines-SAO 2011

Geriatric Oncology – Chronic Health Conditions

Geriatric Oncology-Death Rates in Elders

Copyright restrictions may apply. Walter, L. C. et al. JAMA 2001;285:2750-2756.

Upper, Middle, and Lower Quartiles of Life Expectancy for Women and Men at Selected Ages

Geriatric Oncology at TJUH (35% over age 70)

2014 TJUH Geriatric Patients by system

•Digestive 25%

•Respiratory 15%

•Breast 12%

•Genitourinary10%

•Leukemia/Lymphoma 8%

•Brain/CNS 8%

2013 TJUH Geriatric Patients by

system

•Digestive 25%

•Respiratory 18%

•Breast 11%

•Genitourinary 10%

•Leukemia/Lymphoma 7%

•Brain/CNS 8%

Geriatric Oncology-Challenges

• Comorbidities increase with age over 70

• Cancer complicates the system further

• Polypharmacy/Pharmacokinetics-dynamics

• Chemotherapy complicates the system further

• Renal Function, distribution volume, albumin and liver

function are key elements.

• Prevalence of Geriatric Syndromes increase with age over

70

Geriatric Oncology-Challenges

• Barriers: Personal/Family/Cultural/Educational

• ambivalence/refusal for treatment

• Cognition, Hearing/Vision loss (Literacy/Numeracy)

• Care Giving/Social Support/Survivorship

• elderly are vulnerable (like pediatrics)

• Spouse? Child? (sandwiching)

• QOL after treatment (tenuous balance)

Geriatric Oncology-Common Geriatric Comorbidities

• Cardiovascular problems

• Renal Insufficiency

• Anemia

• Osteoporosis

• Diabetes

• Malnutrition

• Arthritis

Geriatric Oncology - Common Geriatric Syndromes

• Dementia

• Delirium

• Depression

• Falls

• Incontinence

• Neglect and Abuse

• Failure to thrive

• Persistent dizziness

• Nutritional deficiency

• Vision/ hearing loss

Geriatric Oncology - Chemotherapy Complications of Chemotherapy in Elderly

• Myelosuppression

• Mucositis/GI toxicity (N/V/D and dehydration)

• CHF

• Renal Toxicity

• Central and Peripheral Neurotoxicity

• Cognitive dysfunction

• Delirium

• Cerebellar dysfunction (falls/fractures)

• Hearing loss

Figure 2. Overall Survival for All Patients by Chemotherapy Intensity and Age Group.

(Muss, et al., 2005)

.

(Earle, et al., 2002) ©2002 by American Society of Clinical Oncology

Univariate relationships between patients with stage IV NSCLC being seen by an oncologist

(diamonds, solid line) and subsequently being treated with chemotherapy given that they had

seen an oncologist (squares, broken line). Geographic quintiles were defined based on

increasing likelihood of seeing an oncologist. *P < .05 for trend.

Likelihood of Treatment Decreases with Advancing Age, Co-Morbidity

Geriatric Oncology-Surgical Issues

-Older patients tend to be undertreated

-Higher proportion of emergency procedures with increased morbidity/mortality compared to younger counterparts

-CGA adds considerable info cognitive/functional status

-Need a reliable tool in elderly to predict operative morbidity and mortality (PACE?)

-State of the art surgery equally effective in elders as in younger counterparts considering cancer related survival

-Postoperative care compromised by patient specific issues

i.e. stoma care in patient with severe arthritis/poor eyesight

-Postop delirium increased in elders

increased LOS/morbidity/mortality, Beer’s criteria

R.A. Audiso et.al ESMO-Handbook of Cancer in the Senior Patient 2010

Geriatric Oncology-Surgical Issues

PACE-Preoperative Assessment of Cancer in Elderly -CGA, PS, ASA score, Brief fatigue inventory

-460 consecutive older adults, multivariate analysis

severe fatigue, dependence in IADL, abnormal PS: most important predictors of post surgical

complications

Audisio, RA et.al. Preoperative assessment of surgical risk in oncogeriatric patients Oncologist 2005;

10: 262-268

Pope, D et.al. Pre-operative assessment of cancer in the elderly(PACE): a comprehensive assessment of

underlying characteristics of elderly cancer patients prior to elective surgery Surg Oncol 2006; 15:

189-197

Audisio, RA et.al. Should we operate? Preoperative assessment in elderly cancer patients (PACE) can

help. A SIOG surgical task force prospective study. Crit. Oncol Hematol 2008;65: 156-163

Geriatric Oncology

EVERY geriatric oncology patient will benefit from an initial screen to identify risks that may impact treatment outcomes

• Rodin and Mohile, J Clin Onc, 25:1936-44, 2007,

Exterman and Hurria, J Clin Onc, 25:1824-31, 2007

• Terret et. al. J Clin Onc, 25:1876-81, 2007

Geriatric Oncology-Classification Based on Screening

•Fit

•Vulnerable

•Frail

Geriatric Oncology-Classification Based on Screening

Stages of aging (Comorbidity, Disability, Geriatric Syndromes)

• Fit: treat with antineoplastic therapy

• Vulnerable: Comprehensive Geriatric

Assessment

• Frail: supportive care

Geriatric Oncology-Comprehensive Geriatric Assessment

The tool by which the geriatric team identifies functional impairments, potential adverse drug effects, and opportunities to improve function

Comprehensive Geriatric Assessment (CGA) • Function (ADL, IADL, PS)

• Socioeconomic conditions (caregiver, transport, living conditions, income/finances)

• Geriatric Syndromes

• Comorbidities

• Cognition/Emotional/Distress (ASCO distress therm.)

• Polypharmacy

• Nutrition

Geriatric Oncology-Fit Elders

• Likely to do well with aggressive therapy

• Geriatrician’s role is to support function and monitor co-morbid illness during and after therapy

• Often these patients (and sometimes other members of the healthcare team) need pushing to recognize that they are likely to have a good outcome and realize significant benefit from treatment – we need to help them realize they are not “too old” for cancer treatment

• Risk of under-treatment

Geriatric Oncology-Vulnerable Elders

• Require more comprehensive geriatric assessment to accurately assess risk based on specific disease and proposed treatment

• May benefit from active involvement of geriatrician to closely monitor co-morbid conditions, minimize risk of delirium and functional decline during treatment

• May benefit from modified treatment for malignancy

Geriatric Oncology-Frail Elders

• Predicts difficulty tolerating treatment

• Patient typically best served by a focus on palliation and supportive care

• Geriatricians may take on a major role in supportive care for these patients’ cancer, as well as other comorbidities

• Patients and/or families may need help to understand that the risks of aggressive treatment may actually outweigh the benefits for these patients, but that active palliative and supportive care will be provided

Summary – Complex Treatment Decisions

1) Co-morbid illness adds competing mortality risk

2) Polypharmacy adds risk

3) Poor nutrition adds risk

4) Limited population of elders included in clinical trials/drug

approval testing

-historically excluded above age 70

5) Screening tools not clearly standardized/accepted

6) Evidence based disease-specific treatment guidelines needed

7) Accurate individualized risk/benefit assessment needed

-narrow margin for error

-Standardized chemotherapy toxicity assessment needed

Optimizing Geriatric Oncology Care

• Recognize that cancer behaves differently in older adults.

• Screen for specific risks of treatment before establishing a treatment plan.

• Individualize plan of care to address needs of the patient and family.

• Shared Care including oncology and geriatric interprofessional teams leads

to best outcomes.

Key Issues for Future Research

• What are the key biological factors that make cancer in the elderly

different?

• How do psychosocial issues of aging impact cancer treatment?

• How can we optimize clinical assessment and management within the

interprofessional team?

• Define best practices for treatment of older adults with cancer given

appropriate individualized assessment and treatment goals.

Geriatric Oncology

Geriatric Oncology is

Personalized Medicine!

Geriatric Oncology – Disease Specific Issues

• AML: increased MDR1, unfavorable cytogenetics

• Non-Hodgkin’s Lymphoma(large cell): decreased duration of CR, ? IL-6 related

• Breast Cancer: indolent course, well-differentiated, hormone receptor positive

• Colorectal Cancer: decreased tolerance to fluorinated pyrimidines due to mucositis, undertreated (oxali)

• Lung Cancer (nonSmall cell): decreased tolerance to combined modality therapy in Stage III dz. Doublet better in advanced disease (ASCO 2010)

• Ovarian Cancer: decreased response to chemotherapy.

Prostate Cancer: CHAARTED-E3805 Hormone Sensitive

Metastatic Dz Study design: multicenter, randomized phase 3

Patients and treatment: 790 men (median age 63, range 36-91) with metastatic PCa receiving androgen

deprivation therapy (ADT) randomized to:

Continued ADT alone

ADT + docetaxel-based chemotherapy every 3 weeks for

18 weeks

High Volume: lung or liver metastasis and/or 4 or more bone metastasis(at least 1

beyond pelvis or vertebral column)

Primary endpoint: evaluation of the ability of early chemotherapy to improve OS in

patients receiving ADT for metastatic PCa

In patients with high volume metastatic disease, there is a 17 month

improvement in median overall survival from 32.2 months to 49.2 months

Sweeney C et al. Proc ASCO 2014;Abstract LBA2; Proc ESMO 2014;Abstract 756O.

Prostate Cancer: GETUG-AFU 15 Trial Study Design

Multicenter phase III radomized trial

385 men mPC, no prior hormonal therapy (median age 64, range 57-70)

Hormone therapy alone or in combination with Docetaxel every 3 weeks (max. 9

cycles)

Primary endpoint: Overall Survival

Updated French analysis: 14 month survival difference favoring chemotherapy, did

not reach statistical significance (P= .44)

Retrospective analysis of High Volume Dz. (NCI sponsored study definition) with 183 men

14 month overall survival advantage favoring Docetaxel arm,

Not statistically significant (statistically underpowered subset)

Increased use of Docetaxel for salvage compared to CHAARTED Gravis, G. et.al. 2015 GU Cancers Symposium, Feb. 2015, Abstract 140

Prostate Cancer- What have we learned? CHAARTED- significantly more patients, better powered to assess for OS

difference, fewer patients discontinuing therapy early, maybe better reflection

of OS in patients who can tolerate therapy as compared to GETUG 15.

GETUG 15- significantly higher proportion of patients receiving “salvage”

docetaxel as compared to CHAARTED.

STAMPEDE- (UK, James et.al. ASCO Abst. 5001, May 2015)-2,962 men reported in

the study. Average 10 month overall survival advantage favoring docetaxel/ADT

vs. ADT alone in the metastatic dz patients.

Recommendation- Hormone sensitive mPCa patients should be offered

docetaxel/ADT as part of initial therapy.

Hughes, K. et al. N Engl J Med 2004;351:971-977 Manisha Palta et al. Cancer, January 15, 2015

Breast Cancer: The Use of Adjuvant Radiotherapy in Elderly Patients with

Early-Stage Breast Cancer: Changes in Practice Patterns After Publication of

Cancer and Leukemia Group B 9343

Randomized phase 3 trial

Supported the omission of adjuvant radiotherapy in

elderly women with early-stage breast cancer. SEER data from 2000-2009

40,583 women aged ≥70 years: breast-conserving surgery for

clinical stage 1 (T1N0) hormone positive breast cancer

Analysis of practice patterns of radiotherapy before and after the

publication of the data in 2004

FINDINGS:

• 68.6% of patients treated from 2000-2004 v. 61.7%

of patients treated from 2005- 2009 received some

form of adjuvant radiotherapy (P < .001).

• Reductions regardless of age group, tumor size,

tumor grade, or laterality.

• Decrease in external beam but increase in implant

radiotherapy.

• Nearly two-thirds of women continue to receive

adjuvant radiotherapy

Breast Cancer: Adjuvant Radiation Therapy in

Elderly Patients with Early Stage Breast Cancer Small but statistically significant decline in radiotherapy delivery.

Approximately 65% of women aged > 70 still receive adjuvant radiotherapy.

Questions/Issues Raised:

Long term results of partial or hypo-fractionated XRT may explain ongoing practices?

Medical community’s reaction to withholding a treatment versus adding a treatment? Financial incentives?

Distress and anxiety due to local recurrence that is avoided with well tolerated therapy?

Role of patient compliance with Tamoxifen?

Prime II(I.H Kunkler et.al., Lancet Oncology 2015): significant but modest local control improvement with postoperative radiotherapy in women > 65, tumor < 3cm, node negative, ER/PR positive, grade I/II

Local recurrence is low enough that omission of radiotherapy could be considered for some patients

5 year overall survival and breast cancer-free survival were not statistically different

CLL/SLL

Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia RESONATE trial Ibrutinib significantly improved progression-free survival, overall

survival and response rate among patient with previously treated CLL/SLL compared to Ofatumumab. JC Byrd et al. NEJM 371:3 July 17, 2014

Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions Combining an anti-CD20 antibody with chemotherapy improved

outcomes in patients with CLL and coexisting conditions. Obinutuzumab superior to Rituximab when each combined with Chlorambucil Valentin Goede et al NEJM 370:12 March 20, 2014

Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia R.R. Furman et.al NEJM 370;11 March 13, 2014

o Combination of Idelalisib and Rituxan compared to placebo and Rituxan significantly improved reponse rate progression-free and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy.

Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE-17 Trial Susan O’Brien et.al. ASH

abstract 327, December 2014

o In the largest prospective trial dedicated to the study of del 17p CLL/SLL, Ibrutinib demonstrated marked efficacy in terms of ORR, DOR, and PFS with a favorable risk-benefit profile.

CLL/SLL

CLL/SLL: a paradigm shift? Study Characteristics match population with the disease (current average age

at dx:70 LLS 2014)

Median age: 67, 73, 71, 64 (Historical trials- 58)

Comorbidities: Median CIRS score:

8 (2 studies), >6 in 30% of patients (1 study)

Heavily Pretreated Population Median 2 or 3 prior therapies (3 studies)

Highly active therapeutics with acceptable toxicity profiles:

cytopenias, infusion reactions, infections, diarrhea, hemorrhage,

arrythmia, renal insufficiency, rash, arthralgias

Many FDA approved options:

Newly Diagnosed: (anti CD20) Obinutuzumab, Ofatumumab

Relapsed/Resistant: Ibrutinib (BTK), Idelalisib (PI3kinase)

Journal of Clinical Oncology Special Series: Geriatric

Oncology – August 20, 2014

Review Articles:

o Tumor Types- Prostate, Multiple

Myeloma, AML/MDS, Breast,

Ovary, Lung, Colon,

o Personalized Medicine

o Clinical Trials

o Geriatric Assessment

o Biology of Cancer and Aging

o Biomarkers

o Cognitive effects of Systemic

Therapy

o Supportive Care

o Targeted Therapy in Solid Tumors

o Surgical Considerations

o Cardiac Effects of Anticancer

Therapy

o Cancer Survivorship

o Radiation Therapy

ASCO Quality Care Symposium:

Boston MA – October 17-18 2014

555 professional attendees, 10 countries represented, 311

abstracts presented

General Session: Quality Issues in Vulnerable Populations-Senior

Adult, Multimorbid, Young Survivor and Medically Underserved

Lillian Sung MD, Phd: Quality Issues in Pediatrics

Andrew E. Chapman DO: Healthcare Delivery in Senior Adult Oncology

Patients, “The Silver Oncologic Tsunami” JOP May 2015

Sandra L. Wong MD, MS: Medically Underserved Populations: Disparities in

Quality and Outcomes

Neeraj K. Arora, Phd: Quality Issues for Cancer Patients and Survivors

with Multiple Chronic Conditions: Understanding the Patient’s Perspective

Empower the healthcare workforce

education and training

defined core competencies to practice geriatric-based oncologic care

Development of health care delivery models for older cancer patients

Active participation

promote comprehensive, efficient, patient-centered geriatric oncology care

Develop geriatric oncology based relevant data sets

clinical trials

facilitate informed, shared decision making

Establish new standards of care

psychosocial assessment

early intervention by palliative care

advanced care planning at the time of diagnosis of the older adult with cancer.

ASCO Quality Care Symposium, October 2014 Boston Mass.

Geriatric Oncology: Urgent To-Do List

ASCO Quality Care Symposium

Geriatric Oncology

Jefferson Senior Adult Oncology Center

-history, demographics, access

-clinical structure and function

-first 500 patients

-clinical trials portfolio

Cancer and Aging Research Group

Geriatric Oncology-SAO Center

History

Established September 2010

First Multidisciplinary Geriatric Oncology evaluation center in the tristate area

Model: presented at SIOG 2013, ASCO 2014 and published JGO April 2014

Demographics

All tumor types

Patients age 70 and above

Pre-transplant (Bone Marrow) evaluation age 65 and above

Access

Single phone call to navigator (215) 955-7539

Geriatric Oncology-SAO Center

Multidisciplinary Interprofessional Comprehensive evaluation center.

Navigation, Geriatrics, Nutrition, Social Work, Pharmacy and Medical Oncology

Consultative Service

Session Tuesday Afternoons (Methodist Campus), Friday Mornings (Center City Campus)

Average evaluation time: 2 hours

Average access to evaluation: 3 days

Comprehensive Consultative Report completed within 48 hours of evaluation by all health care professionals

Jefferson Senior Adult Oncology Center

Geriatrics

-Kristine Swartz

-Lauren Hersh

Medical Oncology

-Andrew Chapman

-Amy MacKenzie

Pharmacy

-Gina Nightingale

-Emily Hajjar

Social Work

-Lora Rhodes

Surgery

Nutrition

-Monica Crawford

Navigator

-Jillian Brown(215-955-8516)

Rehabilitation

Radiation Oncology

-Vochita Barad

-Nicole Simone

Psychiatry

-William Jangro

Jefferson Senior Adult Oncology Center

Initial 500 patients evaluated:

Pharmacy- 75% had recommendations to optimize medication regimen

Social Work- 50% of patients recommended asisstance

Nutrition- 60% of patients identified “at risk” for malnutrition

Medical Oncology- 70% of tx plans altered by multi-disciplinary conference

Geriatrics- 80% of evaluations led to changes med regimen/tx plan/referrals

Clinical Trials Portfolio (development) Geriatric Assesment (Chapman)

- Chemotherapy Assessment tool validation study

- Accurate Evaluation of the Senior Adult Oncology Patient (AESOP)

Breast Cancer (Chapman)

- Herceptin/Lapatinib for Metastatic Breast Cancer

Gynecologic Cancer (Zibelli)

- GOG 273 Chemotherapy Toxicity in Elderly Women with Ovarian,

Primary Peritoneal, and Fallopian Tube Cancer

Acute Leukemia (Kasner)

- Phase Ib KX2-391(Src tyrosine kinase inhibitor) for AML

ASCO Prepares for an Aging Nation

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Questions?