Pancreatic Cancer Update - Alberta Health Services · 2019. 4. 5. · Dr. Safiya Karim –...
Transcript of Pancreatic Cancer Update - Alberta Health Services · 2019. 4. 5. · Dr. Safiya Karim –...
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Pancreatic Cancer Update
Safiya Karim, MD, MSc, FRCPC Clinical Assistant Professor
Medical Oncologist Tom Baker Cancer Centre
April 13, 2019
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Faculty/Presenter Disclosure• Speaker: Dr. Safiya Karim
– Pancreatic Cancer
• Relationships with financial sponsors:– Grants/Research Support: – Speakers Bureau/Honoraria:– Consulting Fees:– Patents: – Other:
CFPC CoI Templates: Slide 1 – used in Faculty presentation only.
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Disclosure of Financial Support• This Program is funded through AHS Operational Funding.• This Program has not received financial support.• This Program has not received in-kind support.• Dr. Safiya Karim is presenting at this Program on a voluntary basis.• Potential for conflict(s) of interest: None
CFPC CoI Templates: Slide 2
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Objective
• At the end of this session, participants will be able to analyze data presented and identify how it can assist with patient diagnosis and management of pancreatic cancer.
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Overview
• Epidemiology • Risk Factors• Diagnosis and Screening • Recent advances in medical treatment • Local initiatives
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Pancreatic cancer
Exocrine cancers (>90%)
I.e. Pancreatic ductal adenoca
Acinar adenoca
Pancreatic Neuroendocrine Tumours (pNET)
(<10%)
I.e. Insulinoma, glucagonoma
Gastrinoma, VIPoma
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Incidence Mortality
2017 5,500 4,800
5 yr overall survival = 7%
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More than 50% present with stage IV disease
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Deaths from Pancreatic Cancer Predicted to Increase
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RISK FACTORS
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Risk Factors Modifiable
Cigarette Smoking
Obesity
Diet
Alcohol
Chronic pancreatitis
Obesity
Dietary factors
(H.Pylori/ Hep C. infection)
Non-Modifiable
Age
Sex (M>F)
Ethnicity
Blood Group
Family History (5-10%)
Diabetes
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Impact of Modifiable Risk Factors
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DIAGNOSIS AND SCREENING
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Presenting Signs/ Symptoms
Findings that are associated with advanced disease
Early stage disease may be completely asymptomatic
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Diagnostic work-up
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Biomarkers for detection
• Currently no reliable biomarker
• CA 19-9 • Others under investigation:
– Serum macrophage inhibitory cytokine 1 (MIC-1)– CECAM-1– Span-1
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Screening • Not for general population due to low
incidence and lack of good screening test • Patients at high risk (>5% lifetime risk)
– Familial pancreatic cancer (at least 2 first degree relatives)(5-10%)
– Peutz-Jeugers syndrome (36%)– Familial atypical multiple mole melanoma (17%)– Hereditary pancreatitis (49%) – BRCA2 carrier with 1st degree relative – Lynch syndrome with 1st degree relative
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Screening
• Start at age 40-50 • Premalignant/ malignant lesions • EUS or MRCP/ MRI
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Hereditary Cancer Clinic Referral
• Personal history of pancreatic cancer at any age AND 2 or more 1st degree relatives with breast/ovarian/ pancreatic cancer at any age
• Occasionally will test an unaffected individual with a striking family history (i.e. 3-4 family members with pancreatic cancer)
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ADVANCES IN TREATMENT
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Adjuvant Chemotherapy Trials
• Conko-001– Gemcitabine vs. Observation – mOS 22.8 months vs. 20.2 months (HR 0.76)
• ESPAC-4 – Gemcitabine + Capecitabine vs. Gemcitabine– mOS 28 months vs. 25.5 months (HR 0.82)
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Study Design
1. Patients 18-79 years of age 2.Histologically confirmed R0 or R1
resected pancreatic ductal adenocarcinoma;
3. CA19-9 level < 180 U/mL 4. ≤ 12 wks post surgery;
5. ECOG PS 0/1; 6. No prior chemotherapy or RT
(N = 493)
mFOLFIRINOX*Q2W x 12 cycles
(n = 247†)
Gemcitabine 1000 mg/m2
Day 1, 8, 15 of 28-day cycle x 6 cycles(n = 246‡)
Primary endpoint: DFS, defined as no tumor, metastasis, second cancer, or death
Secondary endpoints: toxicity, OS, cancer-specific survival, metastasis-free survival
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mOS FFX 54.4 months Gem 35.0 months
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Toxicities Main nonhematologic adverse events
‒ Higher rates with mFOLFIRINOX: diarrhea (especially in cycles 1-2; sensory peripheral neuropathy, fatigue, vomiting, mucositis, hand–foot syndrome
‒ Higher rates with gemcitabine: headache, fever, influenzalike symptoms, ALT increase, AST increase; 1 toxic death
Significantly more patients stopped treatment early in mFOLFIRINOX arm (33.6% vs 21.0%, P = .002)
‒ Higher rates due to toxicity, patient decision; gemcitabine more often discontinued due to relapse
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New Standard of Care
• mFOLFIRINOX is the new standard of care in patients with good performance status, Ca 19-9 < 180 U/mL and who are able to receive chemotherapy within 12 weeks of surgery
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Treatment in Metastatic Setting
• Since 2011, no major improvements in palliative treatment – mFOLFIRINOX (mOS ~11 months), Gem-Abraxane
(mOS ~8 months), Gemcitabine (mOS ~6 months)
• 5-FU + liposomal irinotecan (post gemcitabine) – mOS 6.2 months
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Immunotherapy
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Incidence of dMMR (MSI-H)
Uterine/ endometrial >20%
Colorectal 10-15%
Breast 2-5%
Pancreatic adenoca <1%
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LOCAL INITIATIVES
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• Of 1621 patients identified with advanced pancreatic adenoca in Alberta between 2009 and 2016, only 54% were referred to a cancer center
• Older age and higher comorbidity predicted for non-referral
• Non-referred patients had longer hospital stays, more visits with primary care, general surgery and gastroenterology and similar number of ER visits compared to referred patients
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Determining the Diagnostic Interval in Patients with Pancreatic Cancer
• PI: Safiya Karim • Oncology Research Office Grant 2018
• Objective -> To characterize the diagnostic interval from 1st symptom presentation to diagnosis in patients with pancreatic cancer in Alberta and identify factors associated with a longer diagnostic period
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GP visits Specialist visitsER visits Diagnostic imaging
Claims data
To identify the 1st encounter related to pancreatic cancer so as to better understand presenting symptoms, and identify patients who may have a longer diagnostic period
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Summary • Pancreatic cancer continues to have a poor prognosis
partially due to the late stage of presentation • The most significant progress has been made in the
adjuvant setting but will likely only apply to a select group of patients
• Primary prevention and early detection are important in improving survival
• Local initiatives are underway to understand referral patterns and to determine how to decrease time from presentation to diagnosis
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Thank You!
QUESTIONS?