Metastatic Pancreatic Cancer Guidelines (ASCO, 2020)

The guideline update on metastatic pancreatic cancer was released in August 2020 by the American Society of Clinical Oncology.^[1]

Initial Assessment

Perform a multiphase computed tomography scan of the chest, abdomen, and pelvis to assess the extent of disease. Perform other staging studies only as dictated by symptoms.

Evaluate the patient’s baseline performance status (PS), symptom burden, and comorbidity profile.

Discuss the goals of care (including an advance directive), patient preferences, and support systems.

Multidisciplinary collaboration to formulate treatment and care plans and disease management should be the standard of care.

Early testing for actionable genomic alterations is recommended to guide treatment decisions for patients who are likely to be potential candidates for additional treatment after first-line therapy. Both germline and somatic testing for the following are recommended:

Microsatellite instability (MSI)/mismatch repair deficiency (dMMR)
BRCA mutations with known significance
NTRK gene fusions

First-Line Treatment

FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is recommended for patients who meet all of the following criteria:

Eastern Cooperative Oncology Group (ECOG) PS 0-1
Favorable comorbidity profile
Patient preference and a support system for aggressive medical therapy
Access to chemotherapy port and infusion pump management services

Gemcitabine plus nab-paclitaxel is recommended for patients who meet all of the following criteria:

ECOG PS 0-1
Relatively favorable comorbidity profile
Patient preference and a support system for relatively aggressive medical therapy

Gemcitabine alone is recommended for patients who have either an ECOG PS of 2 or a comorbidity profile that precludes more aggressive regimens, and who wish to pursue cancer-directed therapy. The addition of nab-paclitaxel or capecitabine or erlotinib to gemcitabine may be offered, with proactive dose and schedule adjustments to minimize toxicities.

In patients with an ECOG PS of 3 or with poorly controlled comorbid conditions despite ongoing active medical care, cancer-directed therapy should be offered only on a case-by-case basis. Major emphasis should be on optimizing supportive care measures.

Treatment Options After First-Line Therapy

In patients with tumors harboring NTRK fusions, treatment with larotrectinib or entrectinib is recommended.

The programmed death–1 immune checkpoint inhibitor pembrolizumab is recommended as second-line therapy for patients who have tested positive for mismatch repair-deficient or microsatellite instability-high tumors.

In patients who have a germline BRCA1 or BRCA2 mutation and who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks, options for continued treatment include chemotherapy or the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib.

Gemcitabine plus nab-paclitaxel may be offered as second-line therapy to patients who meet all of the following criteria:

First-line treatment with FOLFIRINOX
ECOG PS 0-1
Relatively favorable comorbidity profile
Patient preference and a support system for aggressive medical therapy

Fluorouracil plus nanoliposomal irinotecan or fluorouracil plus irinotecan where the former combination is unavailable, is preferred as a second-line therapy for patients who meet all of the following criteria:

First-line treatment with a gemcitabine-based regimen
ECOG PS 0-1
Relatively favorable comorbidity profile
Patient preference and a support system for aggressive medical therapy
Access to chemotherapy port and infusion pump management services

Fluorouracil plus oxaliplatin may be considered as second-line therapy for patients who meet all of the following criteria:

First-line treatment with gemcitabine plus nab-paclitaxel
ECOG PS 0-1
Relatively favorable comorbidity profile
Patient preference and a support system for aggressive medical therapy
Access to chemotherapy port and infusion pump management services

Gemcitabine or fluorouracil can be considered as second-line therapy for patients who have either an ECOG PS of 2 or a comorbidity profile that precludes more aggressive regimens and who wish to pursue cancer-directed therapy (the addition of nab-paclitaxel to gemcitabine or nanoliposomal irinotecan to fluorouracil may be offered, with proactive dose and schedule adjustments to minimize toxicities).

No data are available to recommend third-line or further therapy with a cytotoxic agent. Clinical trial participation is encouraged.

Palliative Care

Patients with metastatic pancreatic cancer should have a full assessment of symptom burden, psychological status, and social support as early as possible, preferably at the first visit. In most cases, this assessment will indicate a need for a formal palliative care consultation and services.

Treatment of Pain and Other Symptoms

Patients with metastatic pancreatic cancer should be offered aggressive treatment of the pain and symptoms of the cancer and/or cancer-directed therapy.

Follow-Up and Surveillance

For patients on active cancer-directed therapy outside of a clinical trial, imaging to assess first response should be offered at 2 to 3 months from the initiation of therapy. Computed tomography scans with contrast are the preferred modality. Thereafter, clinical assessment, conducted frequently during visits for cancer-directed therapy, should supplant imaging assessment. Routine use of positron emission tomography scans is not recommended. CA19-9 is not considered an optimal substitute for imaging for the assessment of treatment response.

No data exist on the duration of cancer-directed therapy. An ongoing discussion of the goals of care and assessment of treatment response and tolerability should guide decisions to continue or to hold or terminate cancer-directed therapy.

For more information, see Pancreatic Cancer. For more Clinical Practice Guidelines, please go to Guidelines.

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