Metastatic Pancreatic Cancer
Published by American Society of Clinical Oncology (ASCO) · GRADE
Summary
AI-generatedThis ASCO guideline update provides evidence-based recommendations for second-line and maintenance therapies in metastatic pancreatic cancer. It highlights the use of targeted treatments such as PARP inhibitors (olaparib) for patients with germline BRCA mutations and TRK inhibitors (larotrectinib/entrectinib) for patients with NTRK fusions.
Key Takeaways
- 1Early testing for actionable genomic alterations (MSI-H/dMMR, BRCA, NTRK) is recommended for patients likely to be candidates for additional treatment.
- 2Larotrectinib or entrectinib is recommended for patients with tumors harboring NTRK fusions.
- 3Pembrolizumab is recommended as second-line therapy for MSI-H/dMMR tumors.
- 4Olaparib is an option for maintenance therapy in patients with a germline BRCA1/2 mutation who have not progressed after at least 16 weeks of first-line platinum-based chemotherapy.
What's New in This Version
On the basis of a systematic evidence review, recommendations 1.5, 3.1, and 3.3 were added. Minor modifications were made to recommendations 2.3, 3.5, and 3.7 based on Expert Panel consensus. All other recommendations from the previous version (2018) of this guideline are endorsed for this 2020 update.
Key Recommendations
1. Initial Assessment
- 1.1
A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed to assess the extent of disease. Other staging studies should be performed only as dictated by symptoms.
strongEvidence: intermediateevidence based, benefits outweigh harms - 1.2
The baseline performance status (PS), symptom burden, and comorbidity profile of a patient with metastatic pancreatic cancer should be evaluated carefully.
strongEvidence: intermediateevidence based, benefits outweigh harms - 1.3
The goals of care (to include a discussion of an advance directive), patient preferences, and support systems should be discussed with every patient with metastatic pancreatic cancer and his or her caregivers.
strongEvidence: intermediateevidence based, benefits outweigh harms - 1.4
Multidisciplinary collaboration to formulate treatment and care plans and disease management for patients with metastatic pancreatic cancer should be the standard of care.
strongEvidence: intermediateevidence based, benefits outweigh harms - 1.5
Early testing for actionable genomic alterations is recommended for patients who are likely to be potential candidates for additional treatment after first-line therapy. Both germline and tumor (somatic) testing are recommended. This includes testing for microsatellite instability/mismatch repair deficiency, BRCA mutations (excluding variants of unknown significance), and NTRK gene fusions.
stronginformal consensus - 1.6
Every patient with pancreatic cancer should be offered information about clinical trials, which include therapeutic trials in all lines of treatment as well as palliative care, biorepository/biomarker, and observational studies.
strongEvidence: intermediateinformal consensus, benefits outweigh harms
2. First-Line Treatment
- 2.1
FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is recommended for patients who meet all of the following criteria: an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1, favorable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services.
strongEvidence: intermediateevidence based, benefits outweigh harms - 2.2
Gemcitabine plus nab-paclitaxel is recommended for patients who meet all of the following criteria: an ECOG PS of 0 to 1, a relatively favorable comorbidity profile, and patient preference and a support system for relatively aggressive medical therapy.
strongEvidence: intermediateevidence based, benefits outweigh harms - 2.3
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 in this setting, with proactive dose and schedule adjustments to minimize toxicities.
moderateEvidence: intermediateevidence based, benefits outweigh harms - 2.4
Patients with an ECOG PS of 3 or with poorly controlled comorbid conditions despite ongoing active medical care should be offered cancer-directed therapy only on a case-by-case basis. Major emphasis should be on optimizing supportive care measures.
moderateEvidence: intermediateevidence based, benefits outweigh harms
3. Treatment Options After First-Line Therapy
- 3.1
In patients with tumors harboring NTRK fusions, treatment with larotrectinib or entrectinib is recommended.
moderateEvidence: lowevidence based; benefits outweigh harms - 3.2
Programmed death-1 immune checkpoint inhibitor pembrolizumab is recommended as second-line therapy for patients who have tested positive for mismatch repair deficiency or microsatellite instability high.
strongEvidence: highevidence based; benefits outweigh harms - 3.3
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 PARP inhibitor olaparib.
moderateEvidence: lowevidence based; benefits outweigh harms - 3.4
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, an ECOG PS of 0 to 1, a relatively favorable comorbidity profile, and patient preference and a support system for aggressive medical therapy.
moderateEvidence: lowinformal consensus, benefits outweigh harms - 3.5
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, an ECOG PS of 0 to 1, a relatively favorable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services.
moderateEvidence: lowinformal consensus, benefits outweigh harms - 3.6
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, an ECOG PS of 0 to 1, a relatively favorable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services.
moderateEvidence: lowinformal consensus, benefits outweigh harms - 3.7
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 in this setting, with proactive dose and schedule adjustments to minimize toxicities).
moderateEvidence: lowinformal consensus, benefits outweigh harms - 3.8
No data are available to recommend third-line or greater therapy with a cytotoxic agent. Clinical trial participation is encouraged.
moderateEvidence: lowinformal consensus, benefits outweigh harms
4. Palliative Care
- 4.1
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.
strongEvidence: intermediateevidence based, benefits outweigh harms
5. Treatment of Pain and Symptoms
- 5.1
Patients with metastatic pancreatic cancer should be offered aggressive treatment of the pain and symptoms of the cancer and/or cancer-directed therapy.
strongEvidence: intermediateevidence based, benefits outweigh harms
6. Follow-Up and Surveillance
- 6.1
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 for the management of patients with pancreatic cancer is not recommended. CA19-9 is not considered an optimal substitute for imaging for the assessment of treatment response.
strongEvidence: lowinformal consensus, benefits outweigh harms - 6.2
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.
strongEvidence: lowinformal consensus, benefits outweigh harms
Scope & Objectives
Clinical Topic
Metastatic Pancreatic Cancer
Objectives
To provide an update to the ASCO guideline on metastatic pancreatic cancer pertaining to recommendations for therapy options after first-line treatment.
Target Patient Population
Patients with metastatic pancreatic adenocarcinoma
Target Providers
Patient Criteria & Setting
Therapeutic Area
OncologyGuideline Scope
Inclusion Criteria
- Adult patients with metastatic pancreatic cancer
- Patients with cancer of any site testing positive for actionable genetic mutations (BRCA1, BRCA2, NTRK 1/2/3, dMMR, MSI-H) who have undergone first-line therapy
Exclusion Criteria
- Meeting abstracts not published in peer-reviewed journals
- Editorials, commentaries, letters, news articles, case reports, and narrative reviews
- Non-English language publications
Special Populations
Evidence Grading
System: GRADE
Safety & Contraindications
Monitoring Guidance
Imaging (preferably CT with contrast) to assess first response should be offered 2 to 3 months from initiation of therapy. Thereafter, frequent clinical assessment should supplant routine imaging.
Authors & Contributors
Guideline Features
Learning Context
Difficulty
advanced
Learning Paths