Geriatric Oncology Why? Andrew E. Chapman, DO FACP. March 10, 2016

Transcription

1 Geriatric Oncology Why? Andrew E. Chapman, DO FACP March 10, 2016

2 Geriatric Oncology -No Disclosures

3 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

4 Chronologic Age does not equal Physiologic Age

5 Geriatric Oncology Demographics Leading cause death men/women age % 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 % 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

6 Geriatric Oncology Chronic Health Conditions

7 Geriatric Oncology-Death Rates in Elders

8 Upper, Middle, and Lower Quartiles of Life Expectancy for Women and Men at Selected Ages Copyright restrictions may apply. Walter, L. C. et al. JAMA 2001;285:

9 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%

10 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

11 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)

12 Geriatric Oncology-Common Geriatric Comorbidities Cardiovascular problems Renal Insufficiency Anemia Osteoporosis Diabetes Malnutrition Arthritis

13 Geriatric Oncology - Common Geriatric Syndromes Dementia Delirium Depression Falls Incontinence Neglect and Abuse Failure to thrive Persistent dizziness Nutritional deficiency Vision/ hearing loss

14 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

15 Figure 2. Overall Survival for All Patients by Chemotherapy Intensity and Age Group. (Muss, et al., 2005)

16 Likelihood of Treatment Decreases with Advancing Age, Co-Morbidity. 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. (Earle, et al., 2002) 2002 by American Society of Clinical Oncology

17 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

18 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: 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: 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:

19 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: , 2007, Exterman and Hurria, J Clin Onc, 25: , 2007 Terret et. al. J Clin Onc, 25: , 2007

20 Geriatric Oncology-Classification Based on Screening Fit Vulnerable Frail

21 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

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23 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

24 Geriatric Oncology-Fit Elders Likely to do well with aggressive therapy Geriatrician s role is to support function and monitor comorbid 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

25 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

26 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

27 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

28 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.

29 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.

30 Geriatric Oncology Geriatric Oncology is Personalized Medicine!

31 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, welldifferentiated, 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.

32 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.

33 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 GU Cancers Symposium, Feb. 2015, Abstract 140

34 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.

35 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 ,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 v. 61.7% of patients treated from 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 Hughes, K. et al. N Engl J Med 2004;351: Manisha Palta et al. Cancer, January 15, 2015

36 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

37 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

38 CLL/SLL 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.

39 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)

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41 Journal of Clinical Oncology Special Series: Geriatric Oncology August 20, 2014 Review Articles: o Cognitive effects of Systemic Therapy 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 Supportive Care o Targeted Therapy in Solid Tumors o Surgical Considerations o Cardiac Effects of Anticancer Therapy o Cancer Survivorship o Radiation Therapy

42 ASCO Quality Care Symposium: Boston MA October 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

43 Geriatric Oncology: Urgent To-Do List 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.

44 ASCO Quality Care Symposium

45 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

46 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)

47 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

48 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( ) Rehabilitation Radiation Oncology -Vochita Barad -Nicole Simone Psychiatry -William Jangro

49 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

50 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

51 ASCO Prepares for an Aging Nation.

52 Questions?