1. The Provision of Chemotherapy in Hospice John W. Finn MD, FAAHPM Chief Medical Director Hospice of Michigan Terri L. Maxwell APRN, BC-PCM Director of Research, excelleRx, Inc. Doctoral Candidate, University of Pennsylvania

2. Disclaimer The information and the materials included in this presentation are intended for educational use. Review or discussion of any agent does not alter in any way the conditions for use contractually agreed upon and outlined in the Hospice Pharmacia Medication Use Guidelines. This program will not be a focus on the Medication Use Guidelines and is intended for educational purposes.

3. The Provision of Chemotherapy in Hospice: When is it Palliative? John W. Finn MD, FAAHPM Chief Medical Director Hospice of Michigan

4. Not-for-profit since 1980 Statewide (17 program sites) through merger in 1994 20-25% of hospice care provided in Michigan Census 850-900 patients daily Serve approximately 7,000 pts/families/yr Increasingly competitive hospice market Commitment to care for all Development raises approximately $6 million/yr

5. Palliative Chemotherapy Definitions Palliative CTX (incurable malignancy) Patient/Family – hoped-for disease ‘cure’ Medical Oncologist – disease control Hospice Team – symptom control “Is it palliative?”

6. Palliative Chemotherapy “Is it palliative?” Palliative Chemotherapy…is allowed under the HMB One of several “special modalities” listed, provided the intent of treatment is palliative – not curative. No additional MCR payment may be made regardless of cost of the service. Better Questions: “Is the patient terminal?” “How are the needs of this pt/family best met? HMB Eligibility and Coverage

7. Palliative Chemotherapy Cytotoxic Therapy Indiscriminate cellular poisons Damage DNA, cellular machinery Cancer cells vs. normal cells Targeted Therapy Biotechnologic attack on the cancer cell Less toxic (sometimes oral) Considerably more expensive

8. Palliative Chemotherapy Cytotoxic Therapy Primary effect – shrink tumor (CR,PR) Secondary effect – reduce tumor-related Sx improve HR QOL disease-free survival overall survival

9. Palliative Chemotherapy Cytotoxic Therapy Balance benefit vs. likelihood of toxicity (toxicity>>>benefit when KPS <50% or ECOG <3) (avoid treating pts with multiple co-morbidities, lacking social supports) (age by itself is not a factor) B alance tumor responsiveness vs. pt’s health (tx poorly responsive cancers in only otherwise healthy pts) M ost effective chemotherapy is given first (second, third, fourth-line CTX is increasingly less effective)

10. Palliative Chemotherapy Cytotoxic Therapy Subjective response predictive of objective response (i.e. decrease pain, imp. KPS) Converse is likewise true (i.e. inc. pain, dec. KPS implies CTX is not working) Exception to the rule: tumor responds, but pt doesn’t (i.e. in spite of objective response, pt’s health spirals downward)

11. Palliative Chemotherapy Cytotoxic Therapy (oral examples) Emcyt (estramustine) 140 mg caps Hydrea (hydroxyurea) 500 mg caps Temodar (temozolomide) 5,10,100,250 mg caps Xeloda (capecitabine) 150, 500 mg tabs

12. Palliative Chemotherapy Targeted Therapy Newer agents May benefit Sx, QOL, KPS without evidence of tumor shrinkage or enhanced survival (so-called ‘clinical benefit’) Change of tumor microenvironment (dec. cytokines/neurotransmitters, dec. angiogenesis) Ellison,Chevlen,Palliative Chemotherapy, in Berger,Portenoy,Weisman,2cd Ed., P and P of PC&SO,Ch.50, Lippincott, Wms, Wilkins, 1998

13. Palliative Chemotherapy Targeted Therapy (oral examples) Gleevec (imatinib) 100, 400mg tabs Irresa (gefitinib) 250, 500 mg tabs Tarceva (erlotinib) 25, 50,150 mg tabs

14. Palliative Chemotherapy ‘Open Access’ Rationale Cancer patients and families need improved access to hospice services. Though hospice utilization for those with cancer is good, the timeliness is not (decreasing LOS) Cancer patients and families access hospice very late in the course of illness. Newer therapeutic options are delaying hospice admission, making matters worse.

15. Palliative Chemotherapy (Hospice’s Pandora’s Box) Open Access or Open Checkbook?

16. Palliative Chemotherapy Aggressiveness of Cancer Care at EOL (MCR pts with Ca Lung, Breast, Colorectal, Other GI Malignancies from 1993-1996) Inc CTX in last 2 weeks of life (13.8% - 18.5%) Inc ER, Hospitalization, ICU days Inc hospice utilization (28.3% - 38.8%) Inc hospice LOS < 72 hrs (14.3% - 17%) Earle CC, J Clin Oncol, Jan 15, 2004 Earle CC, Proc. ASCO 2006 (#6004)

17. Palliative Chemotherapy Proposed Quality Indicators <10% pts receive CTX in last 14 days of life <2% start new CTX in last 30 days of life <4% have multiple hospitalizations, or ER visits, or admission to ICU in last month of life <17% die in acute care institution At least 55% pts receive hospice services before death <8% with hospice LOS <3 days Earle CC, International J for Quality in Health Care 2005;17(6):505-509

18. Palliative Chemotherapy Quality Oncology Practice Initiative (QOPI) Preliminary report on EOL measures Pilot phase (Summer 2005) Voluntary quality self-assessment Semi-annual chart abstraction on secure web-based application 455 charts abstracted from 22 practices Simone JV, Proc ASCO 2006 (#8573)

19. Palliative Chemotherapy Quality Oncology Practice Initiative (QOPI) Was pain addressed on either of the last two visits prior to death? 85% Was pain rated numerically? 41% Was pt enrolled in a hospice program? 62% Was pt enrolled in hospice at least 7 days before death? 77% Was the pts last dose of chemotherapy given within 14 days prior to death? 12% Simone JV, Proc ASCO 2006 (#8573)

20. Palliative Chemotherapy Quality Cancer Care (10 goals) Consensus Statement of ASCO and ESMO #7 Multi-disciplinary Cancer Care…integration of pc experts, as well as oncology nurses, and social workers…access to counseling for their psychosocial, nutritional and other needs. #10 Pain Management, Supportive, and Palliative Care…access to optimal palliative care and counseling with respect to end- of-life issues. J Clin Oncol, July 20, 2006

21. Palliative Chemotherapy Improving End-Of-Life Care “the MHB severely limits the availability of the quantity and quality of care to beneficiaries who would benefit from end-of- life care…” (‘ terrible choice’ of either/or vs. both/and) NIH State of the Science Conference Dec 6-8, 2004, Bethesda, Maryland http://consensus.nih.gov

22. Palliative Chemotherapy Need for Integration PC/Supportive Oncology + Hospice Aggressive palliative treatments along with the supportive services hospice provides to patient, family. “a new model of interaction…one that emphasizes cooperation rather than conflict… that keeps the focus on the suffering patient.” Spiess, AAHPM Bulletin, Fall 2005

23. Palliative Chemotherapy Chemotherapy Use Among Hospice Cancer Patients at LifePath Hospice and PC, Inc. 18 patient (plus matched controls) - tended to be more recently diagnosed - fewer hospitalizations while on hospice - better self reported outcomes from treatment - reported slightly more symptoms - had lower symptom distress rating scores (MSAS) - QOL similar in both groups (HQLI) Schonwetter RS, J Pall Med, Feb 2005

24. Palliative Chemotherapy New Models of Concurrent Care Project Safe Conduct Ireland Cancer Center/Hospice of Western Reserve Simultaneous Care UC-Davis (Phase I & II agents) NCI Study Project ENABLE Norris Cotton CC/Dartmouth Hitchcock Med Ctr. Palliative Care Project University of Michigan CCC/Hospice of Michigan

25. Palliative Chemotherapy Collaborative Care Management (CCM) Hospice of Michigan Care Collaboration “Triggers” (CTX,XRT,CT/MRI,HD,TPN,Tf,Vent,liq.O2,other) Admission Delay HMD consults with Referring Doc Negotiate a palliative treatment POC (what has pt/family been told/expectations?) (timeline, endpoints, monitoring, follow-up)

26. Palliative Chemotherapy Collaborative Care Management (CCM) (all “triggers”) Admit with proposed tx plan25% Admit with modified tx plan60% Admit without trigger tx<10% Delay5% Do not admit1%

27. Palliative Chemotherapy Collaborative Care Management (CCM) Customer Focus/Referral Source friendly Preferred by Medical Oncologists Sense of Goodwill in the Community Market Differentiation Development Opportunity Hope (psych. distress, non-abandonment)

28. Palliative Chemotherapy Collaborative Care Management (CCM) Reduction in Use and Cost of Therapeutics Less Team ‘Distress’ Appreciated by Most Referring Docs (not all) Perceived by Pt/Family as a QOL Issue A Few Questions by Fiscal Intermediary

29. Palliative Chemotherapy Concluding Remarks Pragmatic Approach to Pall. Chemotherapy in Hospice Offer Guidance - Collaborative Management Hospice Medical Director as Active Participant in POC Treatment Decisions Individualized to the Pt/Family Timeframe and End-Points Determined Pre-Admission

30. Terri L. Maxwell APRN, BC-PCM Director of Research, excelleRx, Inc. Doctoral Candidate, University of Pennsylvania The Provision of Chemotherapy in Hospice: An Analysis of Hospices and Hospice Patients

31. Theoretical Framework Hospice Access Many factors limit access to and utilization of hospice services, but governmental regulations are especially limiting. The Medicare Hospice Benefit enacted in 1982: –Was based upon the notion that care shifts in some linear fashion at the end of life (EOL) and that the goals of therapy are easily distinguished as cure-focused or palliative and –Often compel patients and providers to choose between receiving disease-modifying therapies and hospice care.

32. Theoretical Framework Chemotherapy Treatment Advances Since the 1990s, there has been a growth in the development of nondebilitating palliative chemotherapy agents, making continuing treatment more acceptable for patients. The availability of these less toxic therapies is considered an important factor in patients’ decisions to postpone the election of hospice care and for physicians to delay hospice referral.

33. Palliative Chemotherapy Palliative chemotherapy has been defined as “ the use of antineoplastic medications to affect the cancer and to reduce the adverse signs and symptoms caused either directly or indirectly by the malignant disease process. ” * Using this definition, palliative chemotherapy could be allowable under Medicare guidelines. *Ellison, 1998

34. The Chemotherapy Dilemma for Hospices Hospice programs are faced with making decisions about enrolling patients receiving palliative agents that are not being used to cure the terminal diagnosis, but rather to decrease symptoms associated with the disease. Not all hospices view chemotherapy (even palliative) as hospice appropriate. Current reimbursement rates make it difficult for most hospices to cover the costs associated with chemotherapy

35. Examples of Palliative Chemotherapy Costs Based upon a 150 lb 5’6” female* –Gefitinib (Iressa  )- $60 per day (taken daily) –Capecitabine (Xeloda  )- $108 per day (taken daily for 2 weeks, then one week off and then cycles repeats) –Temozolomide (Temodar  )- $61 per day (taken for 5 days in 28-day cycles) *Costs per www.drugstore.com

36. Background/Significance Chemotherapy has been identified as a barrier to hospice enrollment, which affects overall hospice utilization and hospice length of stay (LOS). Hospice LOS is declining; In 2004, 35% of all patients served by hospice died in 7 days or less. –The median LOS has declined from 29 days in 1995 to 22 days in 2004.

37. Implications of Hospice LOS Changes in LOS have important implications for patients, their caregivers, and hospices –Shorter LOS: Means hospices have a greater proportion of high-cost days, which has contributed to budget shortfalls for many programs. Increases the burden on hospice staff and family members. Decreases the time hospice has to provide care. Decreases caregiver satisfaction with hospice services.

38. Study Purpose 1.To determine if hospice organizational characteristics are associated with the provision of chemotherapy in hospice. 2.To examine differences between chemotherapy and non- chemotherapy patients in hospice, especially with respect to hospice length of stay.

39. Research Design Exploratory, descriptive correlational design using secondary analysis of patients admitted to hospices receiving medication management from Hospice Pharmacia. Sample- –Patients with a diagnosis of brain, breast or lung cancers receiving FDA-approved oral palliative agents specific to their diagnoses: temozolomide (Temodar), capecitabine (Xeloda) and gefitinib (Iressa), respectively. –Admitted to hospice on or after 1/01/03 and discharged or deceased by 6/30/05. Study was approved by University of Pennsylvania IRB

40. Methods excelleRx and the excelleRx database –excelleRx provides pharmacy services to >800 hospice programs and approx. 30% of all US hospice patients through its Hospice Pharmacia (HP) business unit. Avg daily census >75,000 patients. –Hospice programs that contract with HP are nationally representative of other hospice programs. –Data is collected longitudinally as part of the care process that occurs when hospice nurses call pharmacists with requests for medication consultation or medication changes.

41. Variables of Interest Patient Variables –Gender –Age –Race/ethnicity –Diagnosis –Chemotherapy received –Discharge disposition (alive vs. deceased) –Hospice LOS Hospice Variables –Size (based upon average daily census for 2Q‘05 or last available quarter) –Profit status –Geographic region

42. Study Findings

43. Patient Demographics Age on admission to hospice –Mean age- 70 yrs Ethnicity –Caucasian- 79% –Non-Caucasian- 12% (8.4% Black) –Unknown- 11% Discharge status –Deceased (87.2%) –Discharged alive (12.8%) Diagnoses –Brain cancer- 8% –Breast cancer- 18% –Lung cancer- 74% Length of stay –Mean- 41 days –Median- 19 days –26% LOS < 7 days N= 58,154

44. Chemotherapy 1,114 (2%) patients received chemotherapy Chemotherapy received: –Gefitinib (Iressa) (n= 911) –Temozolomide (Temodar) (n= 87) –Capecitabine Xeloda (n= 116)

45. Characteristics of Patients Receiving Chemotherapy in Hospice NO-CHEMOCHEMOP value Age (mean)70 yrs66 yrsP < 0.001 GenderFemale55.8%52.1% P = 0.012** Male44.2%47.9% Ethnicity * Caucasian87.2%86.3% P = 0.698 Non-Caucasian12.8%13.9% Pt StatusDeceased87.2%86.1% P = 0.272 Discharged12.8%14% *Excludes Unknown ** Non-significant after breast ca dx removed

46. LOS Differences for Patients Receiving Chemotherapy No Chemotherapy Mean Median Chemotherapy Mean Median P value* All patients40.7 days 19.0 days 53.8 days 28.0 days < 0.001 Lung cancer39.4 days 18.0 days 48.4 days 26.0 days < 0.001 Breast cancer44.0 days 19.0 days 76.4 days 35.5 days < 0.001 Brain cancer45.0 days 24.0 days 83.7 days 40.5 days < 0.001 * Bivariate analyses of chemo vs. no-chemo using Mann Whitney test

47. Characteristics of Hospice Sample N=544 hospices 237/544 hospices provided chemotherapy (43.6%) Of those who provided chemotherapy, a range of 1 to 62 patients received these agents VariableFrequency (%) Average daily census Small (<50) Medium (50-200) Large (>200) 318 (58.5%) 200 (36.8%) 26 (4.8%) Region of country South Northeast Midwest West 189 (33.8%) 138 (25.4%) 146 (26.8%) 76 (14.0%) Profit status Not-for-profit For-profit 373 (68.8%) 171 (31.4%) Chemotherapy No Yes 307 (56.4%) 237 (43.6%)

48. Characteristics of Hospices Providing Chemotherapy (N=237) VariableN (%) providing chemotherapy P value Average daily census Small <50 Medium 50-200 Large >200 93 (29.2%) 123 (61.2%) 23 (88.5%) <0.001 Region of country South Northeast Midwest West 86 (46.7%) 67 (48.6%) 48 (32.9%) 36 (47.4%) 0.025 Profit status Not-for-profit For-profit 193 (51.7%) 44 (25.7%)<0.001

49. Likelihood of Providing Chemotherapy Logistic regression analyses, controlling for hospice size, profit status, and region, were used to assess the likelihood of being a chemotherapy provider. In the model including ADC, profit status, and region, not-for-profit hospices were almost 5 times more likely to provide chemotherapy compared to for-profit programs, independent of size and region. Controlling for profit status and region, small and medium-sized hospices were much less likely to offer chemotherapy compared to large hospices. Region did not independently add to the prediction of which hospices were chemotherapy providers.

50. Summary of Study Findings A significant number of hospices are providing oral chemotherapy. Large programs and not-for-profit hospices are more likely to provide chemotherapy compared to small and for-profit organizations. Patients who received chemotherapy were on average, younger than the non-chemotherapy group but were no more likely to be discharged from hospice alive. Chemotherapy patients –were in hospice on average 2 weeks longer than those who did not receive chemotherapy, –were less likely to have short stays of a week or less, and –were more likely to be enrolled for at least 2 months.

51. Discussion Longer hospice LOS may indicate improved access for patients who do not need to wait until all therapies are discontinued before entering hospice. Larger hospices may have a financial advantage enabling them to be able to provide chemotherapy based upon “economy of scale” principles. Not-for-profit hospices are more likely to provide chemotherapy –Other studies* have found that for-profit hospices provide fewer non-core services compared to not-for-profit programs, most likely related to differences in business-focused goals associated with profits and efficiencies. *Carlson et al, 2004; McCue & Thompson, 2006

52. Study Implications Greater availability of less toxic chemotherapy coupled with increased acceptance of their use late in the illness is prompting a growing number of hospices to selectively admit patients on chemotherapy. Hospices differ in their ability and willingness to provide these therapies based upon size and profit status. Providing chemotherapy appears to result in earlier referral to hospice, with fewer patients having very short stays. The current payment system is not well designed to support hospices that elect to provide chemotherapy. A change in Medicare’s payment system that explicitly recognizes palliative chemotherapy may increase access to hospice services for patients who elect to continue treatment.

53. Strengths/Limitations of the Study Strengths –Dataset contained actual prescribing information –Able to examine large numbers of hospices and patients (reduces site effect and better enables detection of differences across groups) –Data is relatively current –Included all patients regardless of age Limitations –Data are not collected for study purposes, so some data elements (especially related to therapy outcomes or hospice admission protocols) are not available –Data was missing for some variables (e.g., 11% race is missing) –Findings may not be generalizable beyond selected diagnoses

54. Implications for Future Research The value of providing chemotherapy in hospice has not yet been adequately described or measured. Organizational-level barriers to providing chemotherapy in hospice are still not understood, especially with regards to financial constraints.

55. Implications for Future Research (con’t) More data are needed to better understand patients and families preferences for treatment options and symptom management and support at the end of life, and factors influencing decisions to continue chemotherapy and accept hospice care. Future studies should also evaluate the total costs for patients both on and off chemotherapy to determine the cost-effectiveness (or lack thereof) of these therapies.

56. Thank you for your time and participation! Questions??? For further information about this presentation, please contact: Terri Maxwell tmaxwell@excelleRx.com 215-282-1789