1. How Well Do We Communicate with Patients Concerning Adjuvant Systemic Therapy? A Survey of 150 Colorectal Cancer Survivors Neil Love, MD 1 ; Carma Bylund, PhD 2 ; Neal J Meropol, MD 3 ; John L Marshall, MD 4 ; Steven A Curley, MD 5 ; Lee M Ellis, MD 5 ; Axel Grothey, MD 6 ; Heinz-Josef Lenz, MD 7 ; Leonard B Saltz, MD 2 ; Melanie Elder, BBA 1 ; Kathryn Ault Ziel, PhD 1 ; Douglas Paley, BA 1 ; Ginelle Suarez, BS 1 ; Erin Wall, BS 1 1 Research To Practice, Miami, FL; 2 Memorial Sloan-Kettering Cancer Center, New York, NY; 3 Fox Chase Cancer Center, Philadelphia, PA; 4 Lombardi Comprehensive Cancer Center, Washington, DC; 5 The University of Texas MD Anderson Cancer Center, Houston, TX; 6 Mayo Clinic College of Medicine, Rochester, MN; 7 USC/Norris Comprehensive Cancer Center, Los Angeles, CA

2. Background Clinical decision-making regarding adjuvant chemotherapy for solid tumors presents a substantial patient education challenge to medical oncologists for a number of reasons: The treatment strategy is subtle and challenging to explain to patients. Potential benefits involve complex numeracy. Potential risks of therapy may be substantial. Despite these difficulties, clinicians are regularly called upon to counsel patients about this treatment option, and approximately one third of office visits for US-based medical oncologists relate to adjuvant systemic therapy of breast, colorectal and lung cancer. 1

3. Patterns of Care surveys conducted by our CME group 2 and other similar surveys 3-5 indicate a discrepancy in the way oncologists approach this treatment strategy across tumor types. For example, oncologists are more likely to recommend chemotherapy to a woman with triple- negative breast cancer than to a patient at similar risk with colorectal cancer (Figure 1). Background (continued)

4. How likely are you to recommend adjuvant chemotherapy to a 60-year-old woman with ER-negative breast cancer or colorectal cancer? (% “very likely”) 100% 0% ER- BC CRC = Colorectal Cancer ER-BC = ER-Negative Breast Cancer CRC ER- BC p < 0.01 Survey of 150 Medical Oncologists (6/2006) FIGURE 1:

5. Background (continued) Many factors may contribute to this dichotomy, including a less well-established research database supporting adjuvant therapy in colorectal cancer. However, in breast cancer, a series of patient surveys over the last 20 years has had an important impact on the clinical practice of adjuvant therapy, including a sentinel 1986 Australian study by Coates and Simes 6, 7 of 104 women treated for breast cancer with adjuvant CMF for six months that demonstrated that about half would receive the same therapy again for a one percent improvement in five-year overall survival.

6. As no similar study had been conducted for patients with colorectal cancer, our CME group launched several needs assessment activities to understand the perspectives of people in this clinical situation, including: A 2004 town meeting of survivors of colorectal cancer and their loved ones A 2005 survey of 150 people with varying stages of colorectal cancer 8 Our group initiated the current study to validate and expand on previous findings by exploring the experiences of people with colorectal cancer who have recently received adjuvant chemotherapy. Background (continued)

7. Objectives Evaluate patient attitudes and physician beliefs regarding treatment tradeoffs in colorectal cancer. Document patient expectations of chemotherapy and how these compared to actual experiences.

8. 150 people with colorectal cancer who had received adjuvant chemotherapy in the past five years were recruited through advocacy groups and oncology practices. Methods

9. These participants were asked to: Listen to an audio education program featuring interviews with clinical investigators and patients to provide a standardized information platform. Consider six theoretical case scenarios (Figure 2) and corresponding graphics illustrating changes in risk of relapse associated with adjuvant chemotherapy (Figure 3). Respond whether or not they would undergo their previous chemotherapy regimen again for the treatment benefit described in each scenario. Methods (continued)

10. Participants were also asked to: Complete an in-depth survey about their expectations of and experiences with adjuvant therapy and the quality of the care delivered and information provided by their oncologists. Evaluate the understandability, value and relevance of an audio/web education supplement to information provided in the oncology office. Methods (continued)

11. A companion survey of 150 medical oncologists and 24 GI cancer specialists was conducted, and participants were asked to consider the same six scenarios evaluated by the patients and then estimate the percent of patients in clinical practice they thought would be willing to go through chemotherapy for the benefits described. Methods (continued)

12. Tradeoff Situations Presented Recurrence Risk ScenarioBaselineWith ChemotherapyAbsolute Benefit 150%49%1% 220%19%1% 320%17%3% 450%45%5% 520%15%5% 650%40%10% FIGURE 2:

13. Sample Presentation of Case Scenario Scenario 4 Baseline recurrence risk: 50% Risk with chemotherapy: 45% Would you receive treatment again ? Patients cured because of adjuvant chemotherapy Patients whose cancer would return even though they received adjuvant chemotherapy Patients who were already cured without adjuvant chemotherapy 5 45 50 FIGURE 3: Absolute benefit: 5%

14. Results Demographics (Figure 4) Most participants were diagnosed with colon cancer and had Stage III disease. The median age was 55. 67 percent of the patients were female, 86 percent were Caucasian and 79 percent had some college education. Approximately one half had received adjuvant therapy with oxaliplatin and a fluoropyrimidine, and the other half had mostly received a fluoropyrimidine alone. 87 percent of the participants were free of recurrence at the time of the survey.

15. Demographics Original Cancer Diagnosis Colon Rectum Patient Age (Median = 55) Over 65 Under 50 Gender: 67% female Race: 86% Caucasian Education: 79% with some college 50 to 65 FIGURE 4:

16. Treatment ReceivedStage at Diagnosis Stage III Stage II Fluoropyrimidine Fluoropyrimidine + Oxaliplatin Demographics (continued) Other Unsure FIGURE 4 (continued): 87% of patients were NED

17. Understanding of the audio education program (Figure 5) Most patients stated that they understood the information completely or almost completely despite the relatively sophisticated concepts presented. Most also believed that the program would be relevant and of interest to other patients diagnosed with colorectal cancer. Results (continued)

18. Understanding of the Audio Segments Segment 5 Strategy and Potential Benefits of Adjuvant Therapy Segment 6 Risks of Therapy I understood it completely or almost completely I understood most of it I understood some of it FIGURE 5:

19. Treatment tradeoffs (Figures 6a-6b) More than a third of the patients would be treated again with the chemotherapy regimen they previously received for a one percent reduction in the risk of relapse. More than 10 percent of the patients would not receive treatment again even for a 10 percent reduction in the risk of relapse. The responses of men and women were not statistically different. Results (continued)

20. 1% 50%  49% 1% 20%  19% 3% 20%  17% 5% 50%  45% 5% 20%  15% 10% 50%  40% Reduction in Risk of Recurrence FIGURE 6a: Percent of Patients Who Would Be Treated Again for Various Absolute Reductions in Relapse Rate

21. p = 0.630p = 0.713p = 0.584p = 1.000p = 0.418p = 0.290 1% 50%  49% 1% 20%  19% 3% 20%  17% 5% 50%  45% 5% 20%  15% 10% 50%  40% Reduction in Risk of Recurrence 32% 36% 52% 59% 70% 67% 80% 76% 92% 86% FIGURE 6b: Percent of Patients Who Would Be Treated Again for Various Absolute Reductions in Relapse Rate (continued)

22. Treatment tradeoffs (Figures 6c-7) The responses of patients receiving oxaliplatin- containing regimens compared to other regimens were not statistically different despite the potential increase in side effects and toxicity associated with the addition of oxaliplatin. The tradeoff predictions of practicing oncologists and GI clinical investigators were lower than the responses of the patients surveyed. Results (continued)

23. p = 0.416 p = 0.922 p = 0.230 p = 0.244 p = 0.117 p = 0.448 Reduction in Risk of Recurrence 1% 50%  49% 1% 20%  19% 3% 20%  17% 5% 50%  45% 5% 20%  15% 10% 50%  40% 32% 38% 32% 41% 51% 63% 68% 73% 82% 86% 90% FIGURE 6c: Percent of Patients Who Would Be Treated Again for Various Absolute Reductions in Relapse Rate (continued)

24. Physician Predictions vs Patient Responses 1% 50%  49% 1% 20%  19% 3% 20%  17% 5% 50%  45% 5% 20%  15% 10% 50%  40% Reduction in Risk of Recurrence FIGURE 7: 19% 17% 35% 14% 10% 36% 28% 29% 57% 52% 59% 68% 48% 50% 77% 72% 83% 88% PatientsClinical InvestigatorsMedical Oncologists Would you be treated again for this benefit?

25. Results (continued) Experiences and expectations (Figures 8-10) More than half of the patients expected more GI toxicity and alopecia than they experienced, but more than one third of the patients receiving oxaliplatin-containing regimens experienced more troubling cold intolerance and peripheral neuropathythan they expected.

26. Much more difficult Somewhat more difficult Similar Somewhat easier Much easier Patient Expectations vs Experience How similar was your overall experience with adjuvant chemotherapy compared to what your oncologist told you to expect? FIGURE 8a:

27. How would you rate the following compared to what you expected? Patient Expectations vs Experience (continued) Nausea or Vomiting Hair Loss Not as bad About the same Worse * Patients receiving oxaliplatin-containing regimens Cold Intolerance*Numbness in Fingers and Toes* Not as bad About the same Worse Not as bad About the same Worse Not as bad About the same Worse FIGURES 8b, c, d, e:

28. Results (continued) Experiences and expectations (Figures 8-10) Most patients were satisfied with the quality of care received from their medical oncologists, but fewer were satisfied with the amount of information provided on potential side effects and treatment benefits.

29. Overall Care Provided Patients’ Grading of Their Oncologists Information Provided on Side Effects ABCDFABCDF ABCDFABCDF FIGURE 9:

30. Results (continued) Experiences and expectations (Figures 8-10) Most patients were not offered participation in a clinical trial, and of those who were not, more than 80 percent would have liked to learn about research-based opportunities.

31. 26% 14% 60% Yes, participated No Patient Participation in Clinical Trials Yes, declined Were you offered participation in a clinical trial as part of your treatment? FIGURE 10:

32. Conclusions The perspectives of people with colorectal cancer can be challenging to understand for those not facing the experience firsthand, even oncology professionals. Physicians should consider that potential heterogeneity exists in patient attitudes with regard to the risk-benefit tradeoffs of adjuvant chemotherapy, and individualized treatment decisions should account for the perspectives of that person.

33. Conclusions (continued) Patients’ experiences with the side effects of adjuvant chemotherapy may be quite different than what they expect, and it is important to consider that external information sources such as other patients, friends and relatives may be contributing to potential gaps in physician-patient communication about treatment-related toxicities.

34. These findings are limited by the potential bias introduced because participants had previously decided to receive adjuvant chemotherapy and were generally free of recurrence. However, this survey suggests an opportunity exists to supplement information patients receive from their oncologists. Conclusions (continued)

35. To confirm these findings and explore how improvements may be implemented, the next step will be to conduct a prospective, real-time evaluation of patients going through this decision-making process and to evaluate the impact of an audio/web program to enhance physician-patient communication. Conclusions (continued)

36. References 1. Love N et al. Management of breast cancer in the adjuvant and metastatic settings. Patterns of Care in Medical Oncology 2007;4(1). 2. Love N, Goldberg RM. Management of cancer of the colon and rectum in the adjuvant and metastatic settings. Patterns of Care in Medical Oncology 2006;3(2). 3. Ravdin PM et al. Survey of breast cancer patients concerning their knowledge and expectations of adjuvant therapy. J Clin Oncol 1998;16(2):515-21. 4. Bremnes RM et al. Cancer patients, doctors and nurses vary in their willingness to undertake cancer chemotherapy. Eur J Cancer 1995;31A(12):1955-9. 5. Jansen SJ et al. Patients’ preferences for adjuvant chemotherapy in early-stage breast cancer: Is treatment worthwhile? Br J Cancer 2001;84(12):1577-85. 6. Coates AS, Simes RJ. Patient assessment of adjuvant treatment in operable breast cancer. In: Williams CJ, editor. Introducing new treatments for cancer: Practical, ethical and legal problems. London (UK): Wiley 1992. p 447-58. 7. Simes RJ, Coates AS. Patient preferences for adjuvant chemotherapy of early breast cancer: How much benefit is needed? J Natl Cancer Inst Monogr 2001;(30):146-52. 8. Love N et al. Patient perspectives on trade-offs of adjuvant systemic therapy for stage II and III colon cancer: A survey of 129 people with colorectal cancer. Gastrointestinal Cancers Symposium 2006;Abstract 373.

37. Acknowledgment This work was supported by an education grant from Sanofi-Aventis.