Pancreatic Cancer Update

Safiya Karim, MD, MSc, FRCPC Clinical Assistant Professor

Medical Oncologist Tom Baker Cancer Centre

April 13, 2019

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.

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

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.

Overview

• Epidemiology • Risk Factors• Diagnosis and Screening • Recent advances in medical treatment • Local initiatives

Pancreatic cancer

Exocrine cancers (>90%)

I.e. Pancreatic ductal adenoca

Acinar adenoca

Pancreatic Neuroendocrine Tumours (pNET)

(<10%)

I.e. Insulinoma, glucagonoma

Gastrinoma, VIPoma

Incidence Mortality

2017 5,500 4,800

5 yr overall survival = 7%

More than 50% present with stage IV disease

Deaths from Pancreatic Cancer Predicted to Increase

RISK FACTORS

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

Impact of Modifiable Risk Factors

DIAGNOSIS AND SCREENING

Presenting Signs/ Symptoms

Findings that are associated with advanced disease

Early stage disease may be completely asymptomatic

Diagnostic work-up

Biomarkers for detection

• Currently no reliable biomarker

• CA 19-9 • Others under investigation:

– Serum macrophage inhibitory cytokine 1 (MIC-1)– CECAM-1– Span-1

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

Screening

• Start at age 40-50 • Premalignant/ malignant lesions • EUS or MRCP/ MRI

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)

ADVANCES IN TREATMENT

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)

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

mOS FFX 54.4 months Gem 35.0 months

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

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

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

Immunotherapy

Incidence of dMMR (MSI-H)

Uterine/ endometrial >20%

Colorectal 10-15%

Breast 2-5%

Pancreatic adenoca <1%

LOCAL INITIATIVES

• 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

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

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

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

Thank You!

QUESTIONS?