The American Society of Clinical Oncology (ASCO) has released practice guidelines on the treatment of patients with metastatic pancreatic cancer (J Clin Oncol. 2016;34(23):2784-2796). The guidelines address six overarching clinical questions and provide 17 key recommendations. Experts in the fields of medical, radiation and surgical oncology; gastroenterology; palliative care; and advocacy reviewed evidence from 25 randomized controlled trials to form their recommendations.
The first question asked: After a histopathologic confirmation of pancreatic adenocarcinoma diagnosis, what initial assessment is recommended before initiating any therapy for metastatic pancreatic cancer? The panel agreed on five key recommendations from this question, including that a multiphase computed tomography (CT) scan of the chest, abdomen, and pelvis should be performed to assess extent of disease, with other staging studies to be performed only as dictated by symptoms. Clinicians should carefully evaluate baseline performance status, symptom burden, and comorbidity profiles of patients, and discuss goals of care, patient preferences, and support systems with every patient and his or her caregivers. Disease management by a multidisciplinary team is standard of care, and every patient with pancreatic cancer should be offered information about clinical trials.
The second question focused on the appropriate first-line treatment of patients with metastatic pancreatic cancer. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB)-paclitaxel (adequate comorbidity profile) can be used for patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, based on patient preference and support system available. For patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens, gemcitabine alone is recommended and the addition of capecitabine or erlotinib may be offered. For patients with an ECOG PS ≥3 and poorly controlled comorbid conditions, supportive care should be emphasized, with cancer-directed therapy only being offered on a case-by-case basis.
The third question addressed the appropriate therapy for patients with metastatic pancreatic cancer who experience either disease progression or intolerable toxicity with prior regimens for metastatic pancreatic cancer. The recommendation is for gemcitabine plus NAB-paclitaxel to be offered as second-line therapy for patients who meet four criteria: first-line treatment with FOLFIRINOX, ECOG PS of 0 to 1, relatively favorable comorbidity profile, and patient preference and support system for aggressive medical therapy. Fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan can be offered as second-line therapy for patients who meet five criteria: first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, relatively favorable comorbidity profile, patient preference and support system for aggressive medical therapy, and chemotherapy port and infusion pump management. Gemcitabine or fluorouracil can be considered for patients who have either an ECOG PS 2 or a comorbidity profile that precludes more aggressive regimens. No data are available to recommend third-line (or greater) therapy with a cytotoxic agent, and clinical trial participation is encouraged.
The fourth question addressed when the concept of palliative care should be introduced. The panel concluded that preferably on the first visit, patients should be given a full assessment of symptom burden, psychological status, and social supports, as well as a palliative care referral.
The fifth question produced recommended strategies for relief of pain and symptoms, and advised that all patients with metastatic pancreatic cancer should be offered aggressive treatment for pain and symptoms from their cancer and related treatment. Initial pain management may include non-opioid analgesics, such as paracetamol, while progressive disease may warrant stronger opioids, including tramadol, morphine, or fentanyl; pain relief from analgesics should be assessed at every clinic visit. Tumor proximity to the celiac axis may result in neuropathic pain, necessitating adjuvant treatment with gabapentin, pregabalin, nortriptyline or duloxetine, or inhibition of synaptic pathways via thoracoscopic splanchnicectomy or dehydrated alcohol.
Follow-up care was the focus of the sixth question, and the guidelines recommend that for patients on active cancer-directed therapy outside a clinical trial, imaging to assess first response should be offered at 2 to 3 months from the initiation of therapy, and CT scans with contrast are the preferred modality. Thereafter, clinical assessment, conducted frequently during visits for cancer-directed therapy, should supplant imaging assessment. The guidelines do not recommend the routine use of positron emission tomography (PET) scans, and CA19-9 is not considered an optimal substitute for imaging in assessing treatment response. No data exist on the duration of cancer-directed therapy, and the guidelines emphasize that an ongoing discussion of goals of care and assessment of treatment response and tolerability should guide decisions to continue or hold/terminate cancer-directed therapy.
For the full guidelines, visit www.asco.org/guidelines/MetPc.