Pancreatic cancer
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
resectable (stages 1 and 2)
surgical resection
Surgical resection is the preferred treatment in patients with resectable disease.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85
The nature and extent of the surgery depends on the location and site of the tumour.
The most widely used procedures are the proximal pancreaticoduodenectomy with antrectomy (Kausch-Whipple procedure) or the pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire procedure) for tumours in the head of the pancreas.
Pylorus-preserving pancreaticoduodenectomy may lead to similar quality of life and survival compared with Kausch-Whipple pancreaticoduodenectomy.[78]Hüttner FJ, Fitzmaurice C, Schwarzer G, et al. Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma. Cochrane Database Syst Rev. 2016 Feb 16;(2):CD006053.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006053.pub6/full
http://www.ncbi.nlm.nih.gov/pubmed/26905229?tool=bestpractice.com
[112]Vickers MM, Powell ED, Asmis TR, et al. Comorbidity, age and overall survival in patients with advanced pancreatic cancer - results from NCIC CTG PA.3: a phase III trial of gemcitabine plus erlotinib or placebo. Eur J Cancer. 2012 Jul;48(10):1434-42.
http://www.ncbi.nlm.nih.gov/pubmed/22119354?tool=bestpractice.com
[ ]
How do pylorus-preserving and classic pancreaticoduodenectomy compare in people undergoing surgical treatment of periampullary and pancreatic carcinoma?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1321/fullShow me the answer
Extended lymphadenectomy is associated with increases in adverse effects compared with standard lymphadenectomy, without conferring any survival benefit.[81]Iqbal N, Lovegrove RE, Tilney HS, et al. A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: a meta-analysis of 1909 patients. Eur J Surg Oncol. 2009 Jan;35(1):79-86. http://www.ncbi.nlm.nih.gov/pubmed/18356005?tool=bestpractice.com
pancreatic enzyme replacement ± olanzapine
Treatment recommended for ALL patients in selected patient group
Pancreatic enzyme supplements may be considered to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52. https://academic.oup.com/pmj/article/84/995/478/7026385 http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com [42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85 [125]National Institute for Health and Care Excellence. Pancreatic cancer. Quality statement 4: pancreatic enzyme replacement therapy. Dec 2018 [internet publication]. https://www.nice.org.uk/guidance/qs177/chapter/Quality-statement-4-Pancreatic-enzyme-replacement-therapy
Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Primary options
pancreatin: dose depends on brand; consult specialist for guidance on dose
OR
olanzapine: 2.5 mg orally once daily
preoperative biliary stenting
Additional treatment recommended for SOME patients in selected patient group
Patients with symptoms of cholangitis (or whose definitive surgery is delayed by >10 days due to logistical reasons) may require an internal biliary stent. If a stent is placed before surgery, a self-expanding metal stent should be placed endoscopically.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85
A temporary stent is also recommended in patients undergoing neoadjuvant induction therapy before surgery, in the setting of a clinical trial.
Routine stenting of patients with jaundice before resection is not recommended; there is no improvement in surgical outcome, and it may increase the risk of infective complications.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85 [88]van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:129-137. http://www.nejm.org/doi/full/10.1056/NEJMoa0903230#t=article http://www.ncbi.nlm.nih.gov/pubmed/20071702?tool=bestpractice.com
neoadjuvant radiotherapy or chemoradiotherapy
Additional treatment recommended for SOME patients in selected patient group
Neoadjuvant therapy (treatment given prior to surgery to reduce the size or extent of the tumour, in order to enhance chances of successful surgical removal of all tumour tissue) remains under investigation in pancreatic cancer.
Neoadjuvant combination chemotherapy or fluorouracil-based chemoradiotherapy can be offered to: patients in whom there is a clinical suspicion (but no radiological evidence) of metastatic disease; patients with borderline performance status who could improve with systemic therapy. In one randomised controlled trial of 246 patients with resectable or borderline resectable pancreatic cancer, neoadjuvant chemoradiotherapy, followed by surgery and adjuvant chemotherapy, did not confer a significant overall survival benefit compared with immediate surgery followed by adjuvant chemotherapy. It was, however, associated with significantly better disease-free survival.[93]Versteijne E, Suker M, Groothuis K, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the Dutch randomized phase III PREOPANC Trial. J Clin Oncol. 2020 Jun 1;38(16):1763-73. http://www.ncbi.nlm.nih.gov/pubmed/32105518?tool=bestpractice.com
Technically unresectable tumours are rarely rendered resectable by neoadjuvant therapy.[94]Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082-8. https://ascopubs.org/doi/10.1200/JCO.19.00946 http://www.ncbi.nlm.nih.gov/pubmed/31180816?tool=bestpractice.com [95]Barenboim A, Lahat G, Geva R, et al. Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: an intention to treat analysis. Eur J Surg Oncol. 2018 Oct;44(10):1619-23. http://www.ncbi.nlm.nih.gov/pubmed/30146251?tool=bestpractice.com
Due to limited evidence, there is no standard neoadjuvant regimen. Treatment approaches vary, and subsequent chemoradiotherapy is sometimes included.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Preferred options for neoadjuvant therapy include the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, or gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel), with or without subsequent chemoradiotherapy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified-dose FOLFIRINOX, or gemcitabine plus cisplatin, with or without subsequent chemoradiotherapy, is recommended.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocol for dosing guidelines.
Primary options
FOLFIRINOX
oxaliplatin
and
fluorouracil
and
irinotecan
and
folinic acid
OR
gemcitabine
and
paclitaxel albumin-bound
OR
gemcitabine
and
cisplatin
adjuvant chemotherapy
Treatment recommended for ALL patients in selected patient group
Adjuvant therapy is treatment given after surgery to minimise the risk of relapse due to occult disease. Adjuvant therapy has been shown to improve overall survival in both control and experimental groups in phase 3 clinical trials.[89]Conroy T, Lambert A, Ducreux M. Adjuvant and neoadjuvant approaches in pancreatic cancer. Curr Opin Oncol. 2023 Jul 1;35(4):326-33. http://www.ncbi.nlm.nih.gov/pubmed/37222189?tool=bestpractice.com Patients with resected pancreatic cancer who did not receive neoadjuvant therapy should be offered 6 months of adjuvant chemotherapy.[94]Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082-8. https://ascopubs.org/doi/10.1200/JCO.19.00946 http://www.ncbi.nlm.nih.gov/pubmed/31180816?tool=bestpractice.com
First-line options for adjuvant therapy include mFOLFIRINOX (a modified combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin), or doublet therapy with gemcitabine plus capecitabine.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 [94]Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082-8. https://ascopubs.org/doi/10.1200/JCO.19.00946 http://www.ncbi.nlm.nih.gov/pubmed/31180816?tool=bestpractice.com
Other recommended regimens include: gemcitabine monotherapy; fluorouracil plus folinic acid; and capecitabine monotherapy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 [94]Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082-8. https://ascopubs.org/doi/10.1200/JCO.19.00946 http://www.ncbi.nlm.nih.gov/pubmed/31180816?tool=bestpractice.com
Adjuvant doublet regimen of gemcitabine plus capecitabine is also recommended by the UK National Institute for Health and Care Excellence (NICE), in the absence of concerns for toxicity or tolerance.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85 One multi-centre, open-label randomised trial of 732 patients with resected pancreatic ductal adenocarcinoma found that adjuvant therapy with capecitabine plus gemcitabine significantly improved survival compared with gemcitabine monotherapy (28.0 vs. 25.5 months).[96]Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11;389(10073):1011-24. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32409-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/28129987?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
mFOLFIRINOX
oxaliplatin
and
fluorouracil
and
irinotecan
and
folinic acid
OR
gemcitabine
and
capecitabine
OR
gemcitabine
OR
fluorouracil
and
folinic acid
OR
capecitabine
adjuvant chemoradiotherapy
Additional treatment recommended for SOME patients in selected patient group
Adjuvant chemoradiotherapy remains controversial in incompletely resected cancers. Data from the ESPAC-1 trial and one meta-analysis suggest that chemoradiotherapy seems to prolong survival only in incompletely excised (R1 or R2 resection) cancers.[97]Stocken DD, Büchler MW, Dervenis C, et al. Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005 Apr 25;92(8):1372-81. https://www.nature.com/articles/6602513 http://www.ncbi.nlm.nih.gov/pubmed/15812554?tool=bestpractice.com [98]Butturini G, Stocken DD, Wente MN, et al; Pancreatic Cancer Meta-Analysis Group. Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg. 2008 Jan;143(1):75-83. http://jamanetwork.com/journals/jamasurgery/fullarticle/401321 http://www.ncbi.nlm.nih.gov/pubmed/18209156?tool=bestpractice.com When choice of treatment is chemoradiotherapy, fluorouracil-based chemoradiotherapy with additional systemic gemcitabine is recommended.[99]Picozzi VJ, Pisters PW, Vickers SM, et al. Strength of the evidence: adjuvant therapy for resected pancreatic cancer. J Gastrointest Surg. 2008 Apr;12(4):657-61. http://www.ncbi.nlm.nih.gov/pubmed/18157582?tool=bestpractice.com [100]Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. http://jamanetwork.com/journals/jama/fullarticle/181567 http://www.ncbi.nlm.nih.gov/pubmed/18319412?tool=bestpractice.com [101]Regine WF, Winter KA, Abrams R, et al. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548408 http://www.ncbi.nlm.nih.gov/pubmed/21499862?tool=bestpractice.com
Adjuvant chemotherapy or chemoradiotherapy should only be considered in patients who have adequately recovered from surgery.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication]. https://www.nice.org.uk/guidance/ng85 Treatment should ideally be initiated within 4 to 8 weeks of surgery. However, data relating to the timing of adjuvant chemotherapy suggest that post-operative treatment delays of up to 12 weeks do not adversely affect outcomes, provided 6 cycles of adjuvant chemotherapy are completed.[102]Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014 Feb 20;32(6):504-12. http://ascopubs.org/doi/full/10.1200/jco.2013.50.7657 http://www.ncbi.nlm.nih.gov/pubmed/24419109?tool=bestpractice.com
The role of adjuvant chemotherapy in patients who received neoadjuvant chemotherapy is under investigation.
See local specialist protocol for dosing guidelines.
Primary options
fluorouracil
and
folinic acid
and
gemcitabine
locally advanced unresectable (stage 3)
endoscopic stent insertion or palliative surgery
Locally advanced unresectable disease includes tumours involving nearby structures to an extent that renders them unresectable despite the absence of evidence of metastatic disease. Metastasis to a regional lymph node beyond the field of resection is considered unresectable.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Endoscopic palliation is preferred over surgical approaches.
Patients with biliary obstruction should be offered palliative treatment with endoscopic metal stent insertion into the bile duct.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 Percutaneous biliary drainage (with subsequent internalisation of the drain) or open-biliary enteric bypass may be considered in selected patients with a longer life expectancy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Palliative gastrojejunostomy may be appropriate for patients with gastric outlet or duodenal obstruction and good performance status. If a patient has poor performance status, enteral stenting or venting percutaneous endoscopic gastrostomy should be considered. Biliary drainage should be assured before enteral stent placement.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 If a patient is not a surgical candidate, endoscopic ultrasound-guided gastrojejunostomy should be considered.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
chemotherapy or chemoradiotherapy or stereotactic body radiotherapy or immunotherapy
Treatment recommended for ALL patients in selected patient group
After relief of biliary obstruction and, if required, gastric obstruction, systemic treatment with combination chemotherapy or chemoradiotherapy is given to control the tumour.
Patients with good performance status appear to benefit from the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel), or the NALIRIFOX regimen (liposomal irinotecan, fluorouracil, folinic acid, oxaliplatin).[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].
https://www.nccn.org/guidelines/category_1
[105]Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703.
https://www.nejm.org/doi/10.1056/NEJMoa1304369
http://www.ncbi.nlm.nih.gov/pubmed/24131140?tool=bestpractice.com
[106]Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.
http://www.nejm.org/doi/full/10.1056/NEJMoa1011923#t=article
http://www.ncbi.nlm.nih.gov/pubmed/21561347?tool=bestpractice.com
[107]Kunzmann V, Siveke JT, Algül H, et al. Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Feb;6(2):128-38.
http://www.ncbi.nlm.nih.gov/pubmed/33338442?tool=bestpractice.com
[108]Wainberg ZA, Bekaii-Saab T, Boland PM, et al. First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: a phase I/II study. Eur J Cancer. 2021 Jul;151:14-24.
https://www.ejcancer.com/article/S0959-8049(21)00195-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/33957442?tool=bestpractice.com
[ ]
How does gemcitabine compare with non‐gemcitabine‐containing regimens for people with advanced pancreatic cancer?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2215/fullShow me the answer Although the NALIRIFOX regimen is advantageous over gemcitabine plus nab-paclitaxel, no distinct advantage over the FOLFIRINOX regimen has been noted.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].
https://www.nccn.org/guidelines/category_1
For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified FOLFIRINOX, or gemcitabine plus cisplatin is recommended.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Alternative regimens include: gemcitabine monotherapy; capecitabine monotherapy; gemcitabine plus erlotinib; gemcitabine plus capecitabine; capecitabine plus oxaliplatin (CapeOx); fluorouracil plus folinic acid plus oxaliplatin (OFF); fluorouracil monotherapy; gemcitabine plus nab-paclitaxel plus cisplatin; or gemcitabine plus docetaxel plus capecitabine (GTX).[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
The addition of erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor) remains controversial. Initial studies suggested a very modest survival benefit (2 weeks), but no significant difference in overall survival was observed when patients with locally advanced pancreatic cancer were randomised to gemcitabine or gemcitabine plus erlotinib.[109]Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. http://ascopubs.org/doi/full/10.1200/JCO.2006.07.9525 http://www.ncbi.nlm.nih.gov/pubmed/17452677?tool=bestpractice.com [110]Heinemann V, Vehling-Kaiser U, Waldschmidt D, et al. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104). Gut. 2013 May;62(5):751-9. http://www.ncbi.nlm.nih.gov/pubmed/22773551?tool=bestpractice.com [111]Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. http://www.ncbi.nlm.nih.gov/pubmed/27139057?tool=bestpractice.com
Patients with intermediate performance status may be treated with capecitabine, gemcitabine, or gemcitabine plus nab-paclitaxel.
Monotherapy with gemcitabine is recommended for the first-line treatment for patients with poor performance status or an unfavourable comorbidity profile. Other first-line treatment options include capecitabine or fluorouracil.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Chemoradiotherapy or a short course of stereotactic body radiotherapy (SBRT) can be offered to patients with good or intermediate performance status with local progression (without distant metastases) during or after chemotherapy, or to those who responded to chemotherapy as consolidation therapy to further improve local control.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 Studies investigating the role of chemoradiotherapy or SBRT in the management of locally advanced pancreatic cancer are ongoing.
Other first-line regimens recommended by the National Comprehensive Cancer Network that can be used under certain circumstances for patients with good or intermediate performance status include: dabrafenib plus trametinib for patients with BRAF V600E mutation; entrectinib, larotrectinib, or repotrectinib for patients with tumours that have a neurotrophic tyrosine receptor kinase gene fusion; pembrolizumab for patients who have tested positive for mismatch repair deficiency or microsatellite instability; and selpercatinib for patients who have tumours with RET gene fusion.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocol for dosing guidelines.
Primary options
FOLFIRINOX
oxaliplatin
and
fluorouracil
and
irinotecan
and
folinic acid
OR
NALIRIFOX
irinotecan liposomal
and
fluorouracil
and
folinic acid
and
oxaliplatin
OR
gemcitabine
and
paclitaxel albumin-bound
OR
gemcitabine
OR
capecitabine
OR
gemcitabine
-- AND --
cisplatin
or
capecitabine
or
erlotinib
OR
fluorouracil
OR
OFF
fluorouracil
and
folinic acid
and
oxaliplatin
OR
CapeOx
capecitabine
and
oxaliplatin
OR
gemcitabine
and
paclitaxel albumin-bound
and
cisplatin
OR
GTX
gemcitabine
and
docetaxel
and
capecitabine
Secondary options
dabrafenib
and
trametinib
OR
entrectinib
OR
larotrectinib
OR
repotrectinib
OR
pembrolizumab
OR
selpercatinib
pain management + pancreatic enzyme replacement ± olanzapine
Treatment recommended for ALL patients in selected patient group
Pancreatic pain (abdominal and back pain) can be a troublesome symptom to control.
Pain control should be commenced along 'the analgesic ladder', but opioids are often required to control the pain.
Local pain-management protocols should be consulted for suggested analgesics. Dosing has to be titrated according to individual requirements and symptom relief versus adverse effect balances.
Additional options include using appropriate long-acting opioid analgesics, percutaneous (or endoscopic ultrasound-guided) coeliac block, endoscopic ultrasound-guided coeliac plexus neurolysis (fluoroscopic- or CT-guided if unavailable), or splanchnicectomy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].
https://www.nccn.org/guidelines/category_1
[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
[119]Puli SR, Reddy JB, Bechtold ML, et al. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain: a meta-analysis and systematic review. Dig Dis Sci. 2009 Nov;54(11):2330-7.
http://www.ncbi.nlm.nih.gov/pubmed/19137428?tool=bestpractice.com
[120]Kaufman M, Singh G, Das S, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol. 2010 Feb;44(2):127-34.
http://www.ncbi.nlm.nih.gov/pubmed/19826273?tool=bestpractice.com
[121]Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007519.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007519.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/21412903?tool=bestpractice.com
[122]Amr YM, Makharita MY. Comparative study between 2 protocols for management of severe pain in patients with unresectable pancreatic cancer: one-year follow-up. Clin J Pain. 2013 Sep;29(9):807-13.
http://www.ncbi.nlm.nih.gov/pubmed/23917696?tool=bestpractice.com
[123]Okita M, Otani K, Gibo N, et al. Systematic review and meta-analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer. Pain Pract. 2022 Sep;22(7):652-61.
http://www.ncbi.nlm.nih.gov/pubmed/35748531?tool=bestpractice.com
[ ]
How does celiac plexus block affect compare with other analgesics in adults with pancreatic cancer pain?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.92/fullShow me the answer However, NICE in the UK recommends against using splanchnicectomy in people with pancreatic cancer.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
[Evidence C]0db01237-cf04-4cf3-8491-60aeb8af6867guidelineCWhat are the effects of interventional techniques in the management of pain from pancreatic cancer?[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
The American Society for Gastrointestinal Endoscopy (ASGE) suggests coeliac plexus neurolysis as an adjunct to analgesics in patients with unresectable pancreatic cancer and abdominal pain.[124]ASGE Standards of Practice Committee, Machicado JD, Sheth SG, et al. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis and management of solid pancreatic masses: summary and recommendations. Gastrointest Endosc. 2024 Nov;100(5):786-96.
http://www.ncbi.nlm.nih.gov/pubmed/39387777?tool=bestpractice.com
Pancreatic enzyme supplements should be used to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52. https://academic.oup.com/pmj/article/84/995/478/7026385 http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com [125]National Institute for Health and Care Excellence. Pancreatic cancer. Quality statement 4: pancreatic enzyme replacement therapy. Dec 2018 [internet publication]. https://www.nice.org.uk/guidance/qs177/chapter/Quality-statement-4-Pancreatic-enzyme-replacement-therapy
Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Primary options
pancreatin: dose depends on brand; consult specialist for guidance on dose
OR
olanzapine: 2.5 mg orally once daily
metastatic (stage 4)
endoscopic stent insertion or palliative surgery
Endoscopic palliation is preferred over surgical approaches.
Patients with biliary obstruction should be offered palliative treatment with endoscopic metal stent insertion into the bile duct.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 Percutaneous biliary drainage (with subsequent internalisation of the drain) or open-biliary enteric bypass may be considered in selected patients with a longer life expectancy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Palliative gastrojejunostomy may be appropriate for patients with gastric outlet or duodenal obstruction and good performance status. If a patient has poor performance status, enteral stenting or venting percutaneous endoscopic gastrostomy should be considered. Biliary drainage should be assured before enteral stent placement.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 If a patient is not a surgical candidate, endoscopic ultrasound-guided gastrojejunostomy should be considered.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
chemotherapy or immunotherapy
Treatment recommended for ALL patients in selected patient group
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), capecitabine, or erlotinib (an oral HER1/EGFR tyrosine kinase inhibitor) may be added to gemcitabine, with proactive dose and schedule adjustments to minimise adverse effects.[43]Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol. 2020 Aug 5:JCO2001364. https://ascopubs.org/doi/10.1200/JCO.20.01364?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/32755482?tool=bestpractice.com
The preferred regimen for patients with good performance status is FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) or modified-dose FOLFIRINOX, or gemcitabine plus nab-paclitaxel.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].
https://www.nccn.org/guidelines/category_1
[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
[113]Conroy T, Ducreux M, ESMO Guidelines Committee. ESMO Clinical Practice Guideline Express Update on the management of metastatic pancreatic cancer. ESMO Open. 2025 Apr;10(4):104528.
https://www.esmoopen.com/article/S2059-7029(25)00397-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/40287191?tool=bestpractice.com
[ ]
How does gemcitabine compare with non‐gemcitabine‐containing regimens for people with advanced pancreatic cancer?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2215/fullShow me the answer In phase 3 trials, both regimens improved survival compared with gemcitabine alone.[105]Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703.
https://www.nejm.org/doi/10.1056/NEJMoa1304369
http://www.ncbi.nlm.nih.gov/pubmed/24131140?tool=bestpractice.com
[106]Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.
http://www.nejm.org/doi/full/10.1056/NEJMoa1011923#t=article
http://www.ncbi.nlm.nih.gov/pubmed/21561347?tool=bestpractice.com
FOLFIRINOX is recommended as a first-line treatment by the UK National Institute for Health and Care Excellence (NICE) for people who are still active or only slightly restricted from physical activity (Eastern Cooperative Oncology Group performance status of 0-1).[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
NICE recommends gemcitabine plus nab-paclitaxel for untreated metastatic adenocarcinoma of the pancreas in adults, restricted to use where other combination treatments are unsuitable and gemcitabine monotherapy would otherwise be given.[114]National Institute for Health and Care Excellence. Paclitaxel as albumin-bound nanoparticles with gemcitabine for untreated metastatic pancreatic cancer. Sep 2017 [internet publication].
https://www.nice.org.uk/guidance/ta476
The NALIRIFOX regimen (liposomal irinotecan, fluorouracil, folinic acid, oxaliplatin) is another tolerable option for patients with metastatic disease with good performance status.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 [113]Conroy T, Ducreux M, ESMO Guidelines Committee. ESMO Clinical Practice Guideline Express Update on the management of metastatic pancreatic cancer. ESMO Open. 2025 Apr;10(4):104528. https://www.esmoopen.com/article/S2059-7029(25)00397-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/40287191?tool=bestpractice.com [108]Wainberg ZA, Bekaii-Saab T, Boland PM, et al. First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: a phase I/II study. Eur J Cancer. 2021 Jul;151:14-24. https://www.ejcancer.com/article/S0959-8049(21)00195-7/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33957442?tool=bestpractice.com One randomised open-label phase 3 study (NAPOLI-3) has reported statistically significant improvement in overall survival and progression-free survival with NALIRIFOX compared with gemcitabine plus nab-paclitaxel in patients with metastatic pancreatic cancer.[115]ClinicalTrials.gov. A study to assess the effectiveness and safety of irinotecan liposome injection, 5-fluorouracil/leucovorin plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared to nab-paclitaxel+gemcitabine treatment (NAPOLI 3). Aug 2023 [internet publication]. https://clinicaltrials.gov/study/NCT04083235 [116]Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-81. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01366-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/37708904?tool=bestpractice.com Although the NALIRIFOX regimen is advantageous over gemcitabine plus nab-paclitaxel, no distinct advantage over the FOLFIRINOX regimen has been noted.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
For known BRCA1/2 or PALB2 mutations, FOLFIRINOX, modified FOLFIRINOX, or gemcitabine plus cisplatin is recommended.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Other recommended options for patients with metastatic disease with good performance status include: gemcitabine monotherapy; gemcitabine plus erlotinib; gemcitabine plus capecitabine; gemcitabine plus nab-paclitaxel plus cisplatin; capecitabine plus oxaliplatin (CapeOx); fluorouracil plus folinic acid plus oxaliplatin (OFF); or gemcitabine plus docetaxel plus capecitabine (GTX).[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Patients with intermediate performance status may be treated with: gemcitabine plus nab-paclitaxel; capecitabine monotherapy; gemcitabine monotherapy; fluorouracil plus folinic acid plus oxaliplatin (FOLFOX); fluorouracil plus folinic acid plus irinotecan (FOLFIRI); or capecitabine plus oxaliplatin (CapeOx).[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
The preferred option for patients with metastatic cancer having a poor performance status is palliative and best supportive care, as chemotherapy often provides limited benefit.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1 Treatment options that may be considered include gemcitabine, capecitabine, or fluorouracil monotherapy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Other first-line regimens recommended by the National Comprehensive Cancer Network that can be used under certain circumstances for patients with good or intermediate performance status include: dabrafenib plus trametinib for patients with BRAF V600E mutation; entrectinib, larotrectinib, or repotrectinib for patients with tumours that have a neurotrophic tyrosine receptor kinase gene fusion; pembrolizumab for patients who have tested positive for mismatch repair deficiency or microsatellite instability; and selpercatinib for patients who have tumours with RET gene fusion. Except for selpercatinib, all other options can be considered in patients with poor performance status.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
See local specialist protocol for dosing guidelines.
Primary options
gemcitabine
and
paclitaxel albumin-bound
OR
FOLFIRINOX
oxaliplatin
and
fluorouracil
and
irinotecan
and
folinic acid
OR
NALIRIFOX
irinotecan liposomal
and
fluorouracil
and
folinic acid
and
oxaliplatin
OR
gemcitabine
OR
gemcitabine
-- AND --
cisplatin
or
capecitabine
or
erlotinib
OR
gemcitabine
and
paclitaxel albumin-bound
and
cisplatin
OR
GTX
gemcitabine
and
docetaxel
and
capecitabine
OR
CapeOx
capecitabine
and
oxaliplatin
OR
capecitabine
OR
OFF or FOLFOX
oxaliplatin
and
fluorouracil
and
folinic acid
OR
FOLFIRI
fluorouracil
and
folinic acid
and
irinotecan
OR
fluorouracil
Secondary options
dabrafenib
and
trametinib
OR
entrectinib
OR
larotrectinib
OR
repotrectinib
OR
pembrolizumab
OR
selpercatinib
pain management + pancreatic enzyme replacement ± olanzapine
Treatment recommended for ALL patients in selected patient group
Pancreatic pain (abdominal and back pain) can be a troublesome symptom to control.
Pain control should be commenced along 'the analgesic ladder', but opioids are often required to control the pain.
Local pain-management protocols should be consulted for suggested analgesics. Dosing has to be titrated according to individual requirements and symptom relief versus adverse effect balances.
Additional options include using appropriate long-acting opioid analgesics, percutaneous (or endoscopic ultrasound-guided) coeliac block, endoscopic ultrasound-guided coeliac plexus neurolysis (fluoroscopic- or CT-guided if unavailable), or splanchnicectomy.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication].
https://www.nccn.org/guidelines/category_1
[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
[119]Puli SR, Reddy JB, Bechtold ML, et al. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer pain: a meta-analysis and systematic review. Dig Dis Sci. 2009 Nov;54(11):2330-7.
http://www.ncbi.nlm.nih.gov/pubmed/19137428?tool=bestpractice.com
[120]Kaufman M, Singh G, Das S, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer. J Clin Gastroenterol. 2010 Feb;44(2):127-34.
http://www.ncbi.nlm.nih.gov/pubmed/19826273?tool=bestpractice.com
[121]Arcidiacono PG, Calori G, Carrara S, et al. Celiac plexus block for pancreatic cancer pain in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007519.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007519.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/21412903?tool=bestpractice.com
[122]Amr YM, Makharita MY. Comparative study between 2 protocols for management of severe pain in patients with unresectable pancreatic cancer: one-year follow-up. Clin J Pain. 2013 Sep;29(9):807-13.
http://www.ncbi.nlm.nih.gov/pubmed/23917696?tool=bestpractice.com
[123]Okita M, Otani K, Gibo N, et al. Systematic review and meta-analysis of celiac plexus neurolysis for abdominal pain associated with unresectable pancreatic cancer. Pain Pract. 2022 Sep;22(7):652-61.
http://www.ncbi.nlm.nih.gov/pubmed/35748531?tool=bestpractice.com
[ ]
How does celiac plexus block affect compare with other analgesics in adults with pancreatic cancer pain?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.92/fullShow me the answer However, NICE in the UK recommends against using splanchnicectomy in people with pancreatic cancer.[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
[Evidence C]0db01237-cf04-4cf3-8491-60aeb8af6867guidelineCWhat are the effects of interventional techniques in the management of pain from pancreatic cancer?[42]National Institute for Health and Care Excellence. Pancreatic cancer in adults: diagnosis and management. Feb 2018 [internet publication].
https://www.nice.org.uk/guidance/ng85
The American Society for Gastrointestinal Endoscopy (ASGE) suggests coeliac plexus neurolysis as an adjunct to analgesics in patients with unresectable pancreatic cancer and abdominal pain.[124]ASGE Standards of Practice Committee, Machicado JD, Sheth SG, et al. American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the diagnosis and management of solid pancreatic masses: summary and recommendations. Gastrointest Endosc. 2024 Nov;100(5):786-96.
http://www.ncbi.nlm.nih.gov/pubmed/39387777?tool=bestpractice.com
Palliative radiotherapy may be administered to relieve symptoms of obstruction, bleeding, or pain refractory to analgesia.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Pancreatic enzyme supplements should be used to maintain weight and increase quality of life, together with attention to dietary intake and additional nutritional supplements.[17]Ghaneh P, Costello E, Neoptolemos JP. Biology and management of pancreatic cancer. Gut. 2007 Aug;56(8):1134-52. https://academic.oup.com/pmj/article/84/995/478/7026385 http://www.ncbi.nlm.nih.gov/pubmed/17625148?tool=bestpractice.com [125]National Institute for Health and Care Excellence. Pancreatic cancer. Quality statement 4: pancreatic enzyme replacement therapy. Dec 2018 [internet publication]. https://www.nice.org.uk/guidance/qs177/chapter/Quality-statement-4-Pancreatic-enzyme-replacement-therapy
Patients should be offered nutritional evaluation by a registered dietitian, if available.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Patients with cancer-related anorexia may benefit from daily low-dose olanzapine.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
Primary options
pancreatin: dose depends on brand; consult specialist for guidance on dose
OR
olanzapine: 2.5 mg orally once daily
olaparib
Additional treatment recommended for SOME patients in selected patient group
Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, is approved in the US as a maintenance treatment for use in adults with metastatic pancreatic adenocarcinoma and confirmed or suspected deleterious BRCA1 or BRCA2 germline mutations who have not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. One phase 3 trial showed that in patients whose disease had not progressed during first-line platinum-based chemotherapy, maintenance olaparib significantly increased progression-free survival compared with placebo (7.4 months compared to 3.8 months), in patients with a germline BRCA1 or BRCA2 mutation.[117]Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-27. https://www.doi.org/10.1056/NEJMoa1903387 http://www.ncbi.nlm.nih.gov/pubmed/31157963?tool=bestpractice.com No significant benefit with respect to overall survival has been observed.[118]Kindler HL, Hammel P, Reni M, et al. Overall survival results from the POLO trial: a phase III study of active maintenance olaparib versus placebo for germline BRCA-mutated metastatic pancreatic cancer. J Clin Oncol. 2022 Dec 1;40(34):3929-39. http://www.ncbi.nlm.nih.gov/pubmed/35834777?tool=bestpractice.com There was no difference in overall mortality between the olaparib and placebo groups at an interim data analysis. Adverse events were more common in the olaparib group than the placebo group and included fatigue, nausea, anaemia, abdominal pain, diarrhoea, decreased appetite, constipation, vomiting, back pain, and arthralgia.[117]Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-27. https://www.doi.org/10.1056/NEJMoa1903387 http://www.ncbi.nlm.nih.gov/pubmed/31157963?tool=bestpractice.com
Platinum-sensitive patients with a germline BRCA1 or BRCA2 mutation may continue treatment with chemotherapy or proceed to maintenance therapy with olaparib. The patient and clinician should make a shared decision, considering response to chemotherapy, toxicities, patient preference, clinical evidence, and cost.[43]Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol. 2020 Aug 5:JCO2001364. https://ascopubs.org/doi/10.1200/JCO.20.01364?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/32755482?tool=bestpractice.com
See local specialist protocol for dosing guidelines.
Primary options
olaparib
metastasis-directed therapy
Additional treatment recommended for SOME patients in selected patient group
Under rare circumstances, metastasis-directed therapy may be considered at a high-volume centre for patients with indolent/oligometastatic disease.[1]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma [internet publication]. https://www.nccn.org/guidelines/category_1
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