Metastatic Pancreatic Cancer
Publication Date: August 5, 2020
Last Updated: March 14, 2022
Recommendations
Initial Assessment
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. (EB, B, S, I)
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The baseline performance status (PS), symptom burden, and comorbidity profile of a patient with metastatic pancreatic cancer should be evaluated carefully. (EB, B, S, I)
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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. (EB, B, S, I)
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Multidisciplinary collaboration to formulate treatment and care plans and disease management for patients with metastatic pancreatic cancer should be the standard of care. (EB, B, S, I)
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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. Results of testing can lead to therapies, such as poly (ADP-ribose) polymerase inhibitors, programmed death-1 checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies. Genomic testing is recommended as part of an initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy (see Treatment Options 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. Results of testing can lead to therapies, such as poly (ADP-ribose) polymerase inhibitors, programmed death-1 checkpoint inhibitor therapy, TRK fusion inhibitors, and clinical trials of targeted therapies. Genomic testing is recommended as part of an initial assessment to ensure that the results of testing are available at the time of treatment decision where applicable after first-line therapy (see Treatment Options After First-Line Therapy)
Qualifying statement.
The decision to test for actionable genomic alterations should involve a discussion between the patient and physician regarding the frequency of actionable findings, treatment implications of testing results, and genetic counseling related to germline testing. ASCO has previously developed a provisional clinical opinion on Evaluating Susceptibility to Pancreatic Cancer that contains recommendations for germline genetic testing.
The decision to test for actionable genomic alterations should involve a discussion between the patient and physician regarding the frequency of actionable findings, treatment implications of testing results, and genetic counseling related to germline testing. ASCO has previously developed a provisional clinical opinion on Evaluating Susceptibility to Pancreatic Cancer that contains recommendations for germline genetic testing.
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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. (IC, B, S, I)
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First-Line Treatment
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. (EB, B, S, I)
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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. (EB, B, S, I)
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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. (EB, B, M, I)
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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. (EB, B, M, I)
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Treatment Options After First-Line Therapy
In patients with tumors harboring NTRK fusions, treatment with larotrectinib or entrectinib is recommended. (EB, B, M, L)
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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. (EB, B, S, H)
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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. (EB, B, M, L)
Qualifying statement.
For the group of platinum-sensitive patients included in Recommendation 3.3, the decision to continue treatment with chemotherapy or proceed to maintenance therapy with olaparib should be based on a discussion between the patient and the oncologist, including consideration of whether a maximum response and plateau in response to chemotherapy have been achieved, the level of cumulative toxicities associated with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost, and clinical evidence, including a lack of overall survival benefit demonstrated in the POLO randomized controlled trial.
For the group of platinum-sensitive patients included in Recommendation 3.3, the decision to continue treatment with chemotherapy or proceed to maintenance therapy with olaparib should be based on a discussion between the patient and the oncologist, including consideration of whether a maximum response and plateau in response to chemotherapy have been achieved, the level of cumulative toxicities associated with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost, and clinical evidence, including a lack of overall survival benefit demonstrated in the POLO randomized controlled trial.
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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. (IC, B, M, L)
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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. (IC, B, M, L)
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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. (IC, B, M, L)
Qualifying statement.
A phase III trial comparing mFOLFOX6 (infusional fluorouracil, leucovorin, and oxaliplatin) with fluorouracil plus leucovorin demonstrated a higher rate of grade 3 or 4 adverse events and significantly reduced overall survival within the mFOLFOX6 arm of the trial12; however, previous phase III data have demonstrated a benefit with the OFF (oxaliplatin, folinic acid, and fluorouracil) regimen compared with fluorouracil plus leucovorin.5,13 Considering the inconsistency of these results, although fluorouracil plus nanoliposomal irinotecan is preferred, the Expert Panel continues to support the use of fluorouracil plus oxaliplatin as an option when availability of fluorouracil plus nanoliposomal irinotecan is limited or when residual toxicity from first-line therapy or comorbidities preclude the use of fluorouracil plus nanoliposomal irinotecan.
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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) (IC, B, M, L)
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No data are available to recommend third-line or greater therapy with a cytotoxic agent. Clinical trial participation is encouraged. (IC, B, M, L)
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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. (EB, B, S, I)
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Treatment of Pain and Symptoms
Patients with metastatic pancreatic cancer should be offered aggressive treatment of the pain and symptoms of the cancer and/or cancer-directed therapy. (EB, B, S, I)
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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 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. (IC, B, S, L)
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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. (IC, B, S, L)
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Recommendation Grading
Overview
Title
Metastatic Pancreatic Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
August 5, 2020
Last Updated Month/Year
November 1, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
The aim of this work was 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 Provider Population
Medical oncologists, radiation oncologists, surgeons, gastroenterologists, and pathologists
PICO Questions
After first-line therapy, what is the appropriate maintenance therapy or second-line therapy for patients with metastatic pancreatic cancer?
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Hospice, Outpatient, Radiology services
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Assessment and screening, Treatment, Management
Keywords
pancreatic cancer, pancreatic adenocardinoma, metastatic cancer
Source Citation
Sohal DPSS, et al. Metastatic Pancreatic Cancer: ASCO Guideline Update. J Clin Oncol. 2020 August 5 DOI: 10.1200/JCO.20.01364
Sohal DPSS, et al. J Clin Oncol. 2018 May 23. DOI: 10.1200/JCO.2018.78.9636
Supplemental Methodology Resources
Methodology
Number of Source Documents
29
Literature Search Start Date
January 1, 2018
Literature Search End Date
December 31, 2019
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 to 3‐week period. Guideline recommendations available for open comment are posted on asco.org/open‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Gastroenterology, Oncology, Medical Oncology, Surgical Oncology, Radiation Oncology, Oncology, Oncology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency.
Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
What is the appropriate therapy for patients with metastatic pancreatic cancer who experience either disease progression or intolerable toxicity with prior regimens for metastatic pancreatic cancer?
Description of Study Criteria
Inclusion: (1) The population included patients with metastatic pancreatic cancer who experience either disease progression or intolerable toxicity with prior regimens. (2) Studies of the efficacy of systematic treatment options for this patient population were considered for inclusion. Included systemic therapy options were chemotherapy or programmed cell death-1 (PD-1) immune checkpoint blockade. (3) Study design was limited to phase III randomized controlled trials (RCTs) for studies of chemotherapy. There was no limitation placed on study design for studies of PD-1 immune checkpoint blockade. Articles were excluded from the systematic review if they were (1) meeting abstracts not subsequently published in peer-reviewed journals; (2) editorials, commentaries, letters, news articles, case reports, narrative reviews; or (3) published in a non-English language.
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine
eligibility for inclusion in the systematic review of the evidence.
Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect.
Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect.
Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect.
Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations.
Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice.
Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field).
Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak").
No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100