Supportive Care Measures Throughout the Patient s Cancer Journey

Transcription

1 Supportive Care Measures Throughout the Patient s Cancer Journey Matti Aapro, MD Genolier Cancer Center Genolier, Switzerland Thanking World GI Cancer Congress 2018 Supportive Care Across the Disease Continuum: An Important Adjunct to Systemic Therapy Giuseppe Aprile, MD San Bortolo General Hospital Vicenza, Italy

2 Outline The case of Mrs A. Pancras (a fictional name) Symptoms management and quality of life (QoL) Role of early palliative care in the disease course Cancer-related pain Common treatment-related adverse events Thromboembolism in pancreatic cancer Nutrition and specific pancreas issues

3 Mrs A. Pancras This 63-year-old woman has no significant medical history, is a mother of 3, always a housewife, and lives with her healthy 65-year-old husband She presents to the oncology unit with the diagnosis of an adenocarcinoma of the pancreas, which the MDT states is unresectable/locally advanced. She has continuous pain irradiating to her back. The MDT suggests palliative chemotherapy What is missing in this presentation? MDT, multidisciplinary team

4 Mrs A. Pancras This 63-year-old woman has no significant medical history, is a mother of 3, always a housewife, and lives with her healthy 65-year-old husband She presents to the oncology unit with the diagnosis of an adenocarcnoma of the pancreas, which the MDT states is unresectable/locally advanced. She has continuous pain irradiating to her back. The MDT suggests palliative chemotherapy What is missing in this presentation: What are her goals? Has she lost weight? Diabetes or signs of exocrine pancreatic insufficiency? What about her pain?

5 Kaasa S, et al. Lancet Oncol Oct 19. [Epub ahead of print]. What Are Her Goals?

6 Supportive/Palliative Care Impacts QoL for Patients With Cancer Marin Caro MM, et al. Clin Nutr. 2007;26(3):

7 QoL Impacts Survival Outcomes in PCA All patients (N = 2478) Log-rank test P<.001 Follow-Up Time (Months) PCA, pancreatic adenocarcinoma Deng Y, et al. Eur J Cancer. 2018;92:20-32.

8 Overall Survival (%) Lessons From the ESPAC-3 Study P<.001 Time (Months) Overall survival (OS) favored patients who completed the full 6 courses of adjuvant chemotherapy No difference in outcome if chemotherapy is delayed up to 12 weeks, thus allowing adequate time for postoperative recovery Valle JW, et al. J Clin Oncol. 2014;32(6):

9 ESMO, European Society for Medical Oncology Jordan K, et al. Ann Oncol. 2018;29(1): Supportive and Palliative Care

10 Parikh RB, et al. N Engl J Med. 2013;369(24): Early Palliative Care

11 Patients Surviving (%) OS (Proportion) Improved Survival With Early Integration of Palliative Care in Cancer Treatment Months Time (Months) Temel JS, et al. N Engl J Med. 2010;363(8): Bakitas MA, et al. J Clin Oncol. 2015;33(13):

12 ASCO Position ASCO, American Society of Clinical Oncology Ferrell BR, et al. J Clin Oncol. 2017;35(1):

13 Outline The case of Mrs A. Pancras Symptoms management and QoL Role of early palliative care in the disease course Cancer-related pain Common treatment-related adverse events Thromboembolism in pancreatic cancer Nutrition and specific pancreas issues

14 Tracks For Pain Management in PCA Drewes AM, et al. Pancreatology. 2018;18(4): BZD, benzodiazepine; GI, gastrointestinal; HIFU, high-intensity focused ultrasound; NSAID, nonsteroidal anti-inflammatory drug; PCM, personalized cancer medicine; SNRI, serotoninnorepinephrine reuptake inhibitor; TCA, tricyclic; TENS, transcutaneous nerve stimulation

15 Pain Management Has Many Aspects Fallon M, et al. Ann Oncol Jul 24. [Epub ahead of print].

16 What would you do for Mrs A. Pancras pain? 1. Prescribe pain medication and see her again in 1 week 2. Prescribe pain medication and see her again in 24 hours 3. Prescribe pain medication and anxiolytic and see her again in 1 week 4. Refer her to a pain expert to titrate morphine 5. Prescribe pain medication and consider localized pain treatment

17 Recommendation Coeliac Plexus Block appears to be safe and effective for the reduction of pain in patients with pancreatic cancer, with a significant advantage over standard analgesic therapy until 6 months [II, B]. Fallon M, et al. Ann Oncol Jul 24. [Epub ahead of print].

18 Outline The case of Mrs A. Pancras Symptoms management and QoL Role of early palliative care in the disease course Cancer-related pain Common treatment-related adverse events Thromboembolism in pancreatic cancer Nutrition and specific pancreas issues

19 FOLFIRINOX (N = 171) Treatment-Related Side Effects Gemcitabine (N = 171) P Value Event Number of Patients/Total Number (%) Hematologic Neutropenia 75/164 (45.7) 35/167 (21.0) <.001 Febrile neutropenia 9/166 (5.4) 2/169 (1.2).03 Thrombocytopenia 15/165 (9.1) 6/168 (3.6).04 Anemia 13/166 (7.8) 10/168 (6.0) NS Nonhematologic Most Common Grade 3 or 4 AEs Occurring in More Than 5% of Patients in the Safety Population* Fatigue 39/165 (23.6) 30/169 (17.8) NS Vomiting 24/166 (14.5) 14/169 (8.3) NS Diarrhea 21/165 (12.7) 3/169 (1.8) <.001 Sensory neuropathy 15/166 (9.0) 0/169 <.001 Elevated level of alanine aminotransferase 12/165 (7.3) 35/168 (20.8) <.001 Thromboembolism 11/166 (6.6) 7/169 (4.1) NS Conroy T, et al. N Engl J Med. 2011;364(19): Von Hoff DD, et al. N Engl J Med. 2013;369(18): Common AEs of Grade 3 of Higher and Growth-Factor Use Event *Events listed are those that occurred in more than 5% of patients in either group 1 Assessment of the event was made on the basis of laboratory values. 2 Assessment of the event was made on the basis of investigator assessment of treatment-related AEs. 3 Peripheral neuropathy was reported on the basis of groupings of preferred terms defined by standardized queries in the Medical Dictionary for Regulatory Activities nab-paclitaxel + Gemcitabine (N = 421) Gemcitabine Alone (N = 402) AE leading to death, n (%) 18 (4) 18 (4) Grade 3 hematologic AE, n/total N (%) 1 Neutropenia 153/405 (38) 103/388 (27) Leukopenia 124/405 (31) 63/388 (27) Thrombocytopenia 52/405 (13) 36/388 (9) Anemia 52/405 (13) 48/388 (12) Receipt of growth factors, n/total N (%) 110/431 (26) 63/431 (15) Febrile neutropenia, n (%) 2 14 (3) 6 (1) Grade 3 nonhematologic AE occurring in >5% of patients, n (%) 2 Fatigue 70 (17) 27 (7) Peripheral neuropathy 3 70 (17) 3 (1) Diarrhea 24 (6) 3 (1) Grade 3 peripheral neuropathy Median time to onset, days Median time to improvement by 1 grade, days Median time to improvement to grade 1, days 29 NR Use of nab-paclitaxel resumed, n/total N (%) 31/70 (44) NA AE, adverse event; NA, not applicable; NR, not reached; NS, not significant

20 Constipation in advanced cancer Delirium in adult patients with cancer Diarrhea in adult patients with cancer Management of anemia and iron deficiency in patients with cancer Management of infusion reactions to systemic anticancer therapy Management of toxicities from immunotherapy Management of febrile neutropenia MASCC and ESMO consensus guidelines for the prevention of chemotherapy and radiotherapy-induced nausea and vomiting Treatment of dyspnea in patients with advanced cancer An Important Resource Central venous access in oncology Management of oral and gastrointestinal mucosal injury Management of refractory symptoms at the end of life and the use of palliative sedation Advanced care planning in palliative care Bone health in patients with cancer Cancer, fertility, and pregnancy Management of chemotherapy extravasation Cardiovascular toxicity induced by chemotherapy, targeted agents, and radiotherapy Management of cancer pain Management of venous thromboembolism in patients with cancer

21 Cancer-Related Fatigue: Still a Major Issue Distressing, persistent, and sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and that interferes with usual functioning Many guidelines for diagnostic and management (NCCN, ONS, ASCO) Pharmacological and nonpharmacological interventions may be considered after the concomitant factors have been either improved or removed Psychostimulants, corticosteroids, antidepressants, nutraceutical interventions Physical exercise, acupuncture, psychological intervention (meditation, yoga, resilience) NCCN, National Comprehensive Cancer Network; ONS, Oncology Nursing Society

22 Aapro M, et al. Clin Colorectal Cancer. 2017;16(4): One More Resource

23 Outline The case of Mrs A. Pancras Symptoms management and QoL Role of early palliative care in the disease course Cancer-related pain Common treatment-related adverse events Thromboembolism in pancreatic cancer Nutrition and specific pancreas issues

24 Thrombosis and PCA Cancer Sites Associated With the Highest Risk of VTE in Hospitalized Patients (Solid Tumors) Site of Cancer Number % VTE Pancreas Kidney Ovary Lung 107, Stomach VTE, venous thromboembolism Young A, et al. Nat Rev Clin Oncol. 2012;9(8): Khorana AA, et al. Cancer. 2007;110(10):

25 VTE in PCA: Risk Factors, Treatment Khorana Predictive Model for VTE Patient Characteristic Site of cancer Score Very high risk (stomach, pancreas) 2 High risk (lung, lymphoma, gynecologic, genitourinary excluding prostate) Platelet counts 350,000 per mm 3 1 Hemoglobin <10 g/dl or use of ESAs 1 BMI 35 kg/m Treatment of VTE and Secondary Prevention Strategy ASCO 2015 updated recommendation ESMO 2011 recommendation Novel evidence BMI, body mass index; DOAC, direct oral anticoagulant; ESAs, erythropoiesis-stimulating agents; LMWH, low molecular weight heparin; VKA, vitamin K antagonists Khorana AA, et al. Blood. 2008;111(10): Mandala M, et al. Ann Oncol. 2011;22(Suppl 6): Lymann GH, et al. J Clin Oncol. 2015; 33(6): Ay C, et al. ESMO Open. 2017;2(2):e

26 Probability of Thromboembolic Event Cumulative Survival LMWH and Gemcitabine Cumulative Probability of VTE Ocurrence Survival Functions Time Post Randomization (Days) Survival Time (in 30 Day Months) Since Date of Randomization WAD, weight-adjusted dalteparin Maraveyas A, et al. Eur J Cancer. 2012;48(9):

27 LMWH and Gemcitabine Combination Phase III CONKO-004 Trial (N = 312) Pelzer U, et al. J Clin Oncol. 2015;33(18):

28 DOACs Are Noninferior to Subcutaneous LMWH for the Treatment of VTE DOAC, direct oral anticoagulant Raskob GE, et al. N Engl J Med. 2018;378(7): See also: Kahale LA, et al. Cochrane Database Syst Rev. 2018;6:CD Al-Samkari H, et al. Cancers (Basel). 2018;10(8):E271.

29 VTE Primary Prophylaxis for Outpatient Setting? In line with ASCO and ESMO recommendations: No routine VTE prophylaxis Prophylaxis may be considered for select high-risk patients after discussion of risk/benefit with a patient NCCN Guidelines. Accessed 24 September 2018.

30 Outline The case of Mrs A. Pancras Symptoms management and QoL Role of early palliative care in the disease course Cancer-related pain Common treatment-related adverse events Thromboembolism in pancreatic cancer Nutrition and specific pancreas issues

31 Aapro M, et al. Ann Oncol. 2014;25(8):

32 % of Malnourished Patients The Incidence of Malnourishment in PCA N = 1903 Number of Patients Hébuterne X, et al. JPEN J Parenter Enteral Nutr. 2014;38(2):

33 Cumulative Survival (Probability) OS By BMI-Adjusted Weight Loss Grading System BMI-adjusted weight loss grading system P<.001 Time to Death (Months) Martin L, et al. J Clin Oncol. 2015;33(1):90-99.

34 Cancer Cachexia: Understanding the Molecular Basis Argilés JM, et al. Nat Rev Cancer. 2014;14(11):

35 Replacement Therapy: Where Is the Evidence? Dietary treatment Fat Malabsorption Macro/Micronutrient Deficiency Weight Loss Malnutrition Diet WITHOUT fat restriction If severe, difficult to control EPI MCT oil Moderate consumption of insoluble fiber (10 g/d to 15 g/d) Pancreatic enzyme replacement therapy Pancrelipase (25000 U to 150,000 U in each meal +/ U to U if intake at mid-morning/afternoon, preferably in middle of meals) The main reason for treatment failure is usually under-dosing, and doses up to 100,000 U to 150,000 U with each main meal, and up to U if snacks are taken between meals (mid-morning, afternoon, or evening snacks), may be given Monitor vitamins and micro/macronutrient deficiency Monitor (and replace) deficiency of fat-soluble vitamins Vitamin D bone metabolic disease Vitamin E visual disturbances Vitamin K impaired coagulation Vitamin A night vision problems Monitor (and replace) deficiency of vitamin B12/folates Monitor (and replace) deficiency of micronutrients (calcium, magnesium, phosphate, potassium, zinc) Monitor kidney and liver function, albumin Laquente B, et al. Clin Transl Oncol. 2017;19(11): EPI, exocrine pancreatic insufficient; MCT, medium chain triglyceride

36 Arends J, et al. Clin Nutr. 2017;36(5): For Practical Guidance (Until Another Simplified Paper Comes Out)

37 Conclusions Evidence for a survival impact of early palliative and supportive care Pain needs specific approaches Guidance to facilitate treatment is available Oncologists should improve their awareness of VTE prevention and treatment Management of nutritional status during course of disease is key And

38 She also said it: "Supportive Care Makes Excellent Cancer Care Possible" D. Keefe Past-MASCC President

39