Systemic management of pancreatic cancer: Supportive care

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1 Systemic management of pancreatic cancer: Supportive care Snežana Bošnjak Institute for Oncology and Radiology of Serbia Dept. Supportive Oncology & Palliative Care Serbia, Belgrade

2 Integrative Oncology Patient-centered model of care: Integrates disease-directed interventions with patient-family directed interventions (supportive & palliative care) Involves patients in the decision-making process (PROs) Improves patient s QoL and overall clinical outcomes (including survival) Jordan K, Aapro M, Kaasa S, et al. Annal Oncol 2018; 29: Basch E, DealAM, DueckAC et al. JAMA 2017; 318(2): Hui D, Bruera E. Nat Rev Clin Oncol 2016; 13:

3 ESMO position statement on supportive and palliative care Jordan K, et al., Annals of Oncology 29: 36 43, 2018

4 Patient-centered Care (ESMO) The oncologist role is not only to deliver the best quality anticancer treatment but also to consider the impact of the disease and treatment on each patient s life ESMO position paper on supportive and palliative care, Jordan K, et al. Annals of Oncology 2018; 29: 36 43

5 Metastatic Pancreatic Cancer : Patient Centered Care (ASCO, 2018) Assessment: Symptom burden, psychological status, and social supports as early as possible, preferably at the first visit Treatment: Aggressive Tx of the pain and Sx of the cancer and / or the cancer-directed therapy A formal PC consult and services Metastatic Pancreatic Cancer: ASCO Guideline.Sohal DPS et al. J Clin Oncol : Guideline Update. Sohal DPS et al. DOI: /JCO Journal of Clinical Oncology - published online before print May 23, 2018

6 Conceptual Framework for Supportive and Palliative Care Supportive care Palliative care Hospice care No evidence of disease Curable cancer Incurable cancer Bereavement Death Conceptual framework for supportive care, palliative care and hospice care, based on the systematic literature review. Hui D, Bruera E. Nat Rev Clin Oncol 2016; 13:

7 Metastatic Pancreatic Cancer : Supportive Care Guidelines Antiemetics (ESMO, 2016) Oral and GI mucosal injury (ESMO, 2015) Febrile neutropenia (ESMO, 2016) Chemotherapy induced peripheral neuropathy (CIPN) (ASCO, 2014)

8 FOLFIRINOX vs Gemcitabine: AEs Grade 3/4 AE, % Hematologic FOLFIRINOX (n = 171) Gemcitabine (n = 171) P Value Neutropenia <.001 Febrile neutropenia: 43% w/gcsf 5.4% Thrombocytopenia Nonhematologic Fatigue NS Vomiting NS Diarrhea <.001 Sensory neuropathy <.001 Elevated ALT <.001 * Conroy T, et al. N Engl J Med. 2011;364: Slide credit: clinicaloptions.com

9 MPACT: Gemcitabine ± NAB-Paclitaxel AEs Event Gem + NAB-Pacli (n = 421) Gem (n = 402) AE leading to death 4 4 Hematolgic AEs grade 3 Neutropenia 38% 27% Leukopenia 31 % 16 % Thrombocytopenia 13 % 9 % Anemia 13 % 12 % Receipt of growth factors 26 % 15 % Febrile neutropenia 3 % 1 % Nonhematologic AEs grade 3* Fatigue 17 % 7 % Peripheral neuropathy 17 % 1 % Diarrhea 6 % 1 % * 5% of pts. Von Hoff DD, et al. N Engl J Med. 2013;369: Slide credit: clinicaloptions.com

10 Chemotherapy induced nausea and vomiting (CINV) The risk for CINV: FOLFIRINOX: moderate, determined by oxaliplatin / irinotecan Gemcitabine: low Gem+ Nab-Paclitaxel: low Supportive Care Goal: Prevention and control of CINV (0-120h) Gr ¾ vomiting: 15% after FOLFIRINOX

11 Overall risk for nausea & vomiting after chemotherapy Emetogenicity of chemotherapy Patient-related risk factors for CINV* Increased risk Female gender Younger age Morning sickness Anxiety Decreased risk Chemotherapy-naïve Alcohol abuse Disease-associated symptoms & concomitant medications Nausea and vomiting due to advanced cancer, the use of opioids for pain Roila F et al. MASCC / ESMO consesus guidelines Ann Oncol (2016) 27 (suppl 5): v119-v133 Dranitsaris G, et al. Annals Oncol 2017; 28:

12 CINV prevention: MEC group ACUTE DELAYED Carboplatin 5HT3+DEX+NK1-5HT3+DEX+APR APR Oxaliplatin 5HT3+DEX DEX* Irinotecan 5HT3+DEX None Roila et al., Annals of Oncology 2016; 27 (Supplement 5): v119 v133 Hesketh PJ, et al. J Clin Oncol 2017; 35(28):3240. Epub 2017 Jul 31. Hesketh Pj, Bosnjak S, Nikolic V, Rapoport B. Support Care Cancer 2011; 19:

13 Febrile neutropenia FOLFIRINOX: Intermediate risk (10-20%); Gemcitabine + Nab-Paclitaxel: Low (< 10%) Gemcitabine: Low (< 10%) Oncologic emergency Supportive Care goal: prevention & empirical treatment FOLFIRINOX: FN: 5% (43.% with GCSF) NAB-Paclitaxel: FN:3% (26% with GCSF) ESMO FN guidelines 2016 NCCN myeloid GFs guidelines Conroy T, et al. N Engl J Med 2011; 364: Hosein PJ, et al. BMC Cancer 2012; 12:199 Von Hoff DD, et al. N Engl J Med. 2013;369:

14 Patient risk factors for FN Age 65 yrs Advanced disease History of prior FN Poor performance / nutritional status Mucositis Liver disfunction (elevated bilirubin), renal disfunction (creatinine clearance < 50 ml/min) ESMO FN Guidelines, 2016 ASCO WBC GFs Guidelines, 2015 NCCN Myeloid GFs Guidelines, 2017

15 FN: Primary prophylaxis Alternative regimens Chemotherapy related FN risk 20% 10%-20% Patient & Disease related risk <10% Prophylactic G-CSF Overall FN risk ESMO 2016 ASCO 2015 NCCN 2017 guidelines NO Prophylac tic G-CSF Risk of FN 20% Risk of FN <20%

16 Neutropenic patient Altered ability to mount a normal immune response Signs & symptoms of infection may be minimal Fever: the principal, the earliest and commonly the only sign of infection Afebrile neutropenic patient who is receiving corticosteroids, NSAIDs Unless recognized & treated, infection can quickly progress to sepsis and death

17 Febrile + neutropenic Afebrile + neutropenic + SIRS or clinical focus of infection Blood cultures & Empirical therapy Modification of empirical regimen : Clinical and / or microbiological demonstration of infection ESMO FN 2016 guidelines

18 RISK PREDICTION FOR FN: MASCC SCORE Burden of illness No/ mild symptoms 5 Moderate symptoms 3 NO hypotension (systolic BP > 90mm Hg) 5 NO COPD 4 Solid tumor or lymphoma with no previous fungal infection 4 No dehydration 3 Outpatient status (at the onset of fever) 3 Age < 60 yrs 2 MASCC score 21: low risk of complications MASCC score < 15: a high mortalty rate

19 Febrile neutropenia Clinical criteria (ASCO, 2018) Risk assessment tools (ie. MASCC score) High risk Low risk: Hospitalisation IV antibiotics: PIP-TZ Cefepim Ceftaz IMP MER ± Aminoglycoside CIP or Levo PO + AM-CL or Clinda PO Outpatient management? ESMO FN 2016; ASCO outpatient management of FN 2018

20 Diarrhoea Assessment: NCI-CTCAE & PROs FOLFIRINOX: 13% (gr 3 & 4) Gemcitabine + Nab-Paclitaxel: 6% (gr 3& 4) Gemcitabine: 1-1.8% (gr 3 & 4) 5FU: bolus IV vs. infusion regimen Irinotecan: acute and late diarrhoea Mechanism: mucositis, panenteritis, enterocolitis Conroy T, et al. N Engl J Med 2011; 364: Von Hoff DD, et al. N Engl J Med. 2013;369: Andreyev J., et al. Lancet Oncol 2014; 15: e447-60

21 Diarrhea: Consequences Volume depletion Renal insufficiency Electrolyte disorders Intestinal hemorrhage / perforation Infection / sepsis (neutropenia!) Abdominal cramps Malnutrition Decrease in QoL, dignity Reduced compliance with treatment

22 Complicated diarrhea: warning signs Fever (is the patient neutropenic?) Abdominal cramping Anorexia, nausea, vomiting Increased weakness Decreased urine output Gastrointestinal bleeding Deteriorated PS Andreyev J., et al. Lancet Oncol 2014; 15: e447-60

23 Diarrhea: treatment Is it complicated (gr 3&4 or 1&2 w/ warning signs)? Pharmacological Loperamide: first-line Tx for CID Octreotide: first & second-line Tx for CID Steroids (oral, IV): immunotherapy Antibiotics Non-pharmacological Fluid and electrolyte replacement Dietary modifications ASCO 2004; MASCC / ISOO 2104 Andreyev et al., Lancet Oncol 2104; 15:

24 Chemotherapy-induced peripheral neuropathy (CIPN) The risk for CIPN: FOLFIRINOX: 9% Gem+ Nab-Paclitaxel: 17% Supportive Care Goal: Screen for CIPN and diagnose it early Conroy T, et al. N Engl J Med 2011; 364: Von Hoff DD, et al. N Engl J Med. 2013;369:

25 CIPN: Oxaliplatin Acute neurotoxicity (sensory & motor Sx) Chronic, cumulative, dose-dependent: mainly sensory, similar to cisplatin Prevention Acute neurotoxicity: avoid exposure to cold No established agents recommended for the prevention of chronic CIPN except decreasing the dose or duration of oxaliplatin ASCO recommends against the use of IV Ca/ Mg supplementation / any other agent Stop & go preventive approach ASCO guidelines Hershman DL, et al. J Clin Oncol. 2014;32:

26 IDEA: Safety AE, % Any event Grade 2 Grade 3/4 Neurotoxicity Grade 2 Grade ¾ Diarrhea Grade 2 Grade 3/4 FOLFOX CAPOX 3 Mos 6 Mos P Value* 3 Mos 6 Mos P Value* *For Chi-squared test for trend. 19 grade 5 events reported < < < <.0001 < Slide credit: clinicaloptions.com Grothey, A.F. Sobrero, A.F. Shields, et al., N Engl J Med 2018; 378:

27 Safety: main nonhematologic AEs Presented By Thierry Conroy at 2018 ASCO Annual Meeting

28 CIPN: Treatment For the treatment of established painful CIPN, clinician may offer duloxetine Inconclusive data, but therapeutic trials reasonable nortriptyline, desipramine pregabalin, gabapentin compounded topical gel (baclofen, amitriptyline HCL, ketamine) ASCO guidelines Hershman DL, et al. J Clin Oncol. 2014;32:

29 Learning to Care