SUMMARY: The American Cancer Society estimates that for 2019, about 56,770 people will be diagnosed with pancreatic cancer and about 45,750 people will die of the disease. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and Western Europe. Unfortunately, unlike other malignancies, very little progress has been made and outcomes for patients with advanced pancreatic cancer, has been dismal with a 5-year survival rate for metastatic pancreatic cancer of approximately 2%.
The ASCO Expert Panel in 2016 published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first and second-line treatment options, palliative and supportive care, and follow-up. This present update incorporated new evidence related to second-line therapy, published between June 2015 and January 2018, for patients who have experienced disease progression or intolerable toxicities during first-line therapy.
INITIAL ASSESSMENT
Recommendation 1.1: A multiphase CT scan of the Chest, Abdomen, and Pelvis should be performed to assess extent of disease. Other staging studies should be performed only as dictated by symptoms.
Recommendation 1.2: The baseline Performance Status, symptom burden, and comorbidity profile of a patient with metastatic pancreatic cancer should be evaluated carefully.
Recommendation 1.3: The goals of care including a discussion of an advance directive, patient preferences, as well as support systems, should be discussed with every patient with metastatic pancreatic cancer and his or her caregivers.
Recommendation 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.
Recommendation 1.5: 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.
FIRST-LINE TREATMENT
Recommendation 2.1: FOLFIRINOX (Leucovorin, Fluorouracil, Irinotecan, and Oxaliplatin) is recommended for patients who meet all of the following criteria: an ECOG PS of 0-1, favorable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services.
Recommendation 2.2: Gemcitabine plus NAB-Paclitaxel is recommended for patients who meet all of the following criteria: an ECOG PS of 0-1, a relatively favorable comorbidity profile, and patient preference and a support system for relatively aggressive medical therapy.
Recommendation 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 either Capecitabine or Erlotinib to Gemcitabine may be considered in this setting.
Recommendation 2.4: Patients with an ECOG PS 3 or more or with poorly controlled comorbid conditions despite ongoing active medical care should be offered cancer-directed therapy only on a case-by-case basis. The major emphasis should be on optimizing supportive care measures.
SECOND-LINE TREATMENT
Recommendation 3.1: Routine testing for dMMR or MSI-H is recommended, using IHC, PCR, or NGS for patients who are considered to be candidates for checkpoint inhibitor therapy.
Recommendation 3.2: PD-1 immune checkpoint inhibitor pembrolizumab is recommended as second-line therapy for patients who have tested positive for dMMR or MSI-H.
Recommendation 3.3: Gemcitabine plus NAB-Paclitaxel can be offered as second-line therapy to patients who had received first-line treatment with FOLFIRINOX, have an ECOG PS of 0-1, with a relatively favorable comorbidity profile, and patient preference and a support system for aggressive medical therapy.
Recommendation 3.4: Fluorouracil plus nanoliposomal Irinotecan, or Fluorouracil plus Irinotecan where the former combination is unavailable, is preferred 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 0-1, 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.
Recommendation 3.5: 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 0-1, 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.
Qualifying statement for Recommendations 3.4 and 3.5: A recent phase III trial comparing mFOLFOX6 with FU + LV demonstrated a higher rate of grade 3 or 4 adverse events and significantly reduced OS within the mFOLFOX6 arm of the trial. However, previous phase III data have demonstrated a benefit with the OFF regimen compared with FU + LV. 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 where the availability of Fluorouracil plus nanoliposomal Irinotecan is limited or where residual toxicity from first-line therapy or comorbidities preclude the use of Fluorouracil plus nanoliposomal Irinotecan.
Recommendation 3.6: 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.
Recommendation 3.7: No data are available to recommend third-line (or greater) therapy with a cytotoxic agent. Clinical trial participation is encouraged
PALLIATIVE CARE
Recommendation 4.1: Patients with metastatic pancreatic cancer should have a full assessment of symptom burden, psychological status, and social supports as early as possible, preferably at the first visit. In most cases, this assessment will indicate a need for a formal palliative care consult and services.
TREATMENT of PAIN and SYMPTOMS
Recommendation 5.1: Patients with metastatic pancreatic cancer should be offered aggressive treatment of the pain and symptoms of the cancer and/or the cancer-directed therapy.
FOLLOW-UP/SURVEILLANCE
Recommendation 6.1: For patients on active cancer-directed therapy outside a clinical trial, imaging to assess first response should be offered at 2-3 months from the initiation of therapy. CT scans with contrast are the preferred modality. Thereafter, clinical assessment, conducted frequently during visits for cancer-directed therapy, should supplant imaging assessment. The routine use of PET 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.
Recommendation 6.2: No data exist on the duration of cancer-directed therapy. An ongoing discussion of goals of care and assessment of treatment response and tolerability should guide decisions to continue or to hold or terminate cancer-directed therapy.
Metastatic Pancreatic Cancer: ASCO Clinical Practice Guideline Update. Sohal DPS, Kennedy EB, Khorana A, et al. J Clin Oncol. 2018;36:2545-2556.
