Key points
- Pancreatic cancer is one of the leading causes of cancer death worldwide, and its global burden has more than doubled over the past 25 years [1].
- Smoking, obesity, diabetes and alcohol use are modifiable risk factors [1]; new-onset diabetes after age 50 can be a warning sign [2].
- For all patients with pancreatic cancer, testing for inherited gene mutations (such as BRCA1 and BRCA2) is recommended; the result matters both for treatment and for the family [3, 4].
- In patients who have had surgery, mFOLFIRINOX chemotherapy has significantly increased overall survival [6, 17].
- In metastatic disease, combination chemotherapy such as FOLFIRINOX or gemcitabine + nab-paclitaxel is the main treatment [9, 10]; the oral drug daraxonrasib, the first RAS inhibitor, is a newer option for previously treated disease that roughly doubled overall survival [13]; personalized mRNA vaccines are still at the research stage [15, 16].
What is pancreatic cancer?
The pancreas is an organ behind the stomach with two main jobs: making digestive enzymes and producing hormones such as insulin that regulate blood sugar. The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which starts in the cells lining the ducts of this organ. Pancreatic neuroendocrine tumors are a less common and usually slower-growing type; they are treated differently and are not covered on this page.
Pancreatic cancer is one of the leading causes of cancer death worldwide, and its burden is rising, largely because of population aging [1]. More than 90% of these tumors carry an activating mutation in a RAS gene (mainly KRAS) [13]; this feature has been a research target for years and has now led to the first effective targeted drugs.
Signs and symptoms
In its early stages, pancreatic cancer usually causes no symptoms, or only vague ones; this is why most patients are diagnosed at an advanced stage [5]. Symptoms that should be taken seriously:
- Jaundice (yellowing) of the skin and the whites of the eyes, often with dark urine, pale stools and itching; especially with tumors in the head of the pancreas that press on the bile duct
- Unexplained weight loss and loss of appetite
- Vague pain in the upper abdomen that may spread to the back
- Fatty, foul-smelling stools that float (because of a lack of digestive enzymes)
- Nausea, feeling full quickly, or severe fatigue
- New-onset diabetes or a sudden worsening of blood sugar control
About 1% of people over 50 who develop new-onset diabetes are diagnosed with pancreatic cancer within three years [2]. The combination of new diabetes + unexplained weight loss is especially concerning; models have been developed to identify the highest-risk people in this group, but they still need further validation and are not general screening tools [2].
Warning signs
If you have any of the following, see a doctor without delay:
- Yellowing of the skin or the whites of the eyes, especially with dark urine, pale stools or itching
- Unexplained weight loss, especially with upper abdominal pain that may spread to the back
- New-onset diabetes after age 50, especially with unexplained weight loss [2]
If you are on treatment, let your care team know promptly about fever, pain, nausea, jaundice or leg swelling.
Risk factors and prevention
Risk factors for pancreatic cancer fall into two groups [1]:
- Modifiable: smoking, obesity, diabetes and alcohol use. Quitting smoking and keeping a healthy weight are the most important preventive steps available.
- Non-modifiable: older age, a family history of pancreatic cancer, inherited mutations in cancer-predisposition genes (such as BRCA1, BRCA2, PALB2, ATM and the Lynch syndrome genes) and hereditary pancreatitis.
Chronic pancreatitis and some pancreatic cysts (such as IPMN) are also associated with a higher risk and need specialist follow-up [5].
Early detection and genetic testing
Screening for pancreatic cancer is not currently recommended for the general population. For people at high risk, however, the approach is different:
- According to the American Society of Clinical Oncology (ASCO), anyone who has two first-degree relatives with pancreatic cancer meets the criteria for “familial pancreatic cancer” and is a candidate for genetic counseling and testing; the benefits and limitations of screening (usually with MRI or endoscopic ultrasound) should be discussed with these individuals [3].
- The US National Comprehensive Cancer Network (NCCN) recommends inherited (germline) genetic testing for all patients with pancreatic cancer, regardless of family history [4].
Finding an inherited BRCA1/2 or PALB2 mutation has two benefits: for the patient, it opens up specific treatment options (platinum-based chemotherapy and PARP inhibitor drugs) [4, 12], and for relatives, it offers an opportunity for testing and prevention [3].
Diagnosis and staging
Diagnostic pathway for pancreatic cancer
- 1
- 2
- 3
- 4
Inherited genetic testing and molecular profiling of the tumor
Germline testing is recommended for all patients, and molecular testing of tumor tissue (such as BRCA, KRAS, MSI/dMMR and NTRK) for advanced or metastatic disease [4].
- 5
| Category | Imaging features | Usual approach |
|---|---|---|
| Resectable | No tumor contact with the major arteries (SMA, celiac trunk, common hepatic artery); no venous contact, or venous contact ≤180° without vein wall irregularity | Surgery followed by adjuvant chemotherapy; in high-risk patients, preoperative chemotherapy can be considered [4, 5] |
| Borderline resectable | Limited contact (≤180°) with the SMA or celiac trunk, or reconstructable venous involvement | Preoperative (neoadjuvant) treatment, then reassessment for surgery [4, 5, 8] |
| Locally advanced | Encasement of more than 180° of the SMA or celiac trunk, or unreconstructable venous involvement; no distant metastases | Systemic chemotherapy, sometimes with radiotherapy; surgery in selected cases with a good response [4, 5] |
| Metastatic | Spread to the liver, peritoneum, lungs or other organs | Systemic therapy based on performance status and molecular markers, together with supportive care [4, 5] |
Exact definitions, especially regarding the blood vessels, differ slightly between guidelines, and resectability should be assessed at a specialized pancreas center.
Treatment options
Surgery
Surgery is the only route to a cure. A Whipple procedure (pancreaticoduodenectomy) is performed for tumors in the head of the pancreas, and a distal pancreatectomy for tumors in the tail; these operations are best done at experienced centers [5].
Adjuvant chemotherapy
After surgery, the mFOLFIRINOX regimen for 24 weeks is the standard for patients with good performance status [6, 17]; for patients who cannot tolerate it, gemcitabine with capecitabine is an alternative [7].
Neoadjuvant (preoperative) treatment
Treatment of metastatic disease
Combination chemotherapy with FOLFIRINOX or gemcitabine + nab-paclitaxel is the first-line treatment [9, 10, 19], and the newer NALIRIFOX regimen has also been effective in the first-line setting [11]. In the second line, the regimen not used in the first line is usually given, that is, gemcitabine-based or fluorouracil-based chemotherapy [5, 19]; the targeted drug daraxonrasib is also a new second-line option, particularly for tumors with a RAS G12 mutation [13, 20].
New treatments: RAS inhibitors and mRNA vaccines
Daraxonrasib: the first anti-RAS drug
Daraxonrasib is an oral drug that blocks the active form of the RAS protein [13]. In the large RASolute 302 trial, in patients whose metastatic pancreatic cancer had already been treated, this drug roughly doubled median overall survival compared with chemotherapy, and far fewer patients stopped treatment because of side effects [13]. Its most common side effects are skin rash, diarrhea, nausea, mouth inflammation (stomatitis) and fatigue [14].
The US Food and Drug Administration (FDA) approved this drug in August 2026 for adults with metastatic pancreatic cancer who have received at least one prior treatment or who are not candidates for multidrug chemotherapy (FDA announcement). Its use as first-line treatment, in earlier stages of the disease and in combination with chemotherapy is still under investigation, as are other RAS inhibitors.
Personalized mRNA vaccine (autogene cevumeran)
Autogene cevumeran is a vaccine made individually for each patient, based on the specific mutations in that patient’s own tumor. In a trial of 16 patients after surgery, the vaccine triggered a strong tumor-specific T-cell response in half of the patients [15], and these cells persisted for up to about three years [16].
The data on the autogene cevumeran vaccine come from a small phase 1 study without a comparison group; comparing responders with non-responders cannot prove that the vaccine improves survival [15, 16]. The vaccine is available only within clinical trials. If you are interested in taking part in a clinical trial, talk to your treating doctor.
Supportive and palliative care
Supportive care is an essential part of pancreatic cancer treatment and should start at diagnosis, alongside anticancer treatment [5]. Its most important components are [5]:
- Pain control: pain medicines used step by step and, for pain that does not respond to them, a celiac plexus nerve block or palliative radiotherapy.
- Treating jaundice and blockage: placing a stent in the bile duct or duodenum by endoscopy.
- Nutrition: pancreatic enzyme replacement taken with meals to improve digestion and prevent weight loss, along with nutritional counseling.
- Psychological and social support for the patient and family, and advance care planning.
What should I do after diagnosis?
Frequently asked questions
Is pancreatic cancer hereditary?
Is there a blood test for early detection?
If the tumor cannot be removed with surgery, does that mean there is no treatment?
How long does chemotherapy after surgery last?
The standard mFOLFIRINOX regimen is usually given once every two weeks for 24 weeks (about 6 months) [6]. Your doctor may adjust the doses depending on how well you tolerate it.
Which patients is daraxonrasib an option for?
In August 2026, this drug was approved in the United States for adults with metastatic pancreatic cancer who have already been treated [13]. Combination chemotherapy remains the main treatment for metastatic disease [9, 10]; talk to your oncologist about where this drug fits in your treatment plan, or about taking part in clinical trials.
Recent evidence and advances (for physicians)
For physicians
| Clinical setting | Regimen/drug | Key evidence |
|---|---|---|
| Adjuvant, ECOG 0–1 | mFOLFIRINOX for 24 weeks | PRODIGE 24/CCTG PA.6, 5-year follow-up [17] |
| Adjuvant, unfit for a four-drug regimen | Gemcitabine + capecitabine | ESPAC-4 [7] |
| Borderline/high-risk resectable | Neoadjuvant therapy (FOLFIRINOX or gemcitabine-based chemoradiotherapy) | PREOPANC [8]; PREOPANC-2 [21] |
| Metastatic, first-line, ECOG 0–1 | FOLFIRINOX | PRODIGE 4/ACCORD 11 [9] |
| Metastatic, first-line, alternative | Gemcitabine + nab-paclitaxel | MPACT [10] |
| Metastatic, first-line, newer regimen | NALIRIFOX | NAPOLI-3 [11] |
| gBRCA1/2, no progression after ≥16 weeks of platinum | Maintenance olaparib | POLO [12, 18] |
| Metastatic, second-line | After FOLFIRINOX: gemcitabine + paclitaxel or nab-paclitaxel, or gemcitabine alone; after gemcitabine-containing regimens: a fluorouracil-based regimen | ESMO 2023 guidelines and 2025 update [5, 19] |
| Metastatic, previously treated (newer option) | Daraxonrasib 300 mg daily | RASolute 302 [13]; ESMO 2026 [20] |
Regimen choice depends on performance status, comorbidities and patient preference. The results of each trial are given in the text below.
New-onset diabetes and early detection
The END-PAC model, built on age at diabetes onset, change in weight and change in blood glucose, identified 7 of 9 patients with pancreatic cancer (78%) in the validation cohort, with a specificity of 85% [2]. The model still requires prospective validation and is not a general screening tool.
Adjuvant and neoadjuvant therapy
In the phase 3 PRODIGE 24/CCTG PA.6 trial (493 patients), adjuvant mFOLFIRINOX improved survival compared with gemcitabine; in the final 5-year report (median follow-up 69.7 months), median disease-free survival was 21.4 vs 12.8 months (HR 0.66), median OS 53.5 vs 35.5 months (HR 0.68) and 5-year OS 43.2% vs 31.4% [17]; the cost of this benefit was grade 3 or 4 adverse events in 75.9% vs 52.9% [6]. For patients unfit for a four-drug regimen, in the phase 3 ESPAC-4 trial, gemcitabine + capecitabine increased median OS from 25.5 to 28.0 months compared with gemcitabine alone (HR 0.82) [7]. In the Dutch PREOPANC trial in resectable and borderline resectable disease, gemcitabine-based neoadjuvant chemoradiotherapy, despite a small difference in median survival (15.7 vs 14.3 months), increased 5-year survival from 6.5% to 20.5% (HR 0.73) [8]. In the phase 3 PREOPANC-2 trial (375 patients with resectable or borderline resectable disease), neoadjuvant FOLFIRINOX did not improve OS compared with the same gemcitabine-based chemoradiotherapy (median 21.9 vs 21.3 months; HR 0.88), and both approaches were considered acceptable [21]. In resectable disease, the benefit of neoadjuvant therapy has not been established: in the phase 2 NORPACT-1 trial, four cycles of preoperative FOLFIRINOX did not improve survival compared with upfront surgery (median OS 25.1 vs 38.5 months) [22]. NCCN prefers neoadjuvant therapy for borderline resectable disease and considers it an option in resectable disease with high-risk features (such as markedly elevated CA19-9, a large primary tumor or large lymph nodes, severe weight loss or pain) [4].
Metastatic disease
In the ACCORD 11 trial, FOLFIRINOX increased median OS from 6.8 to 11.1 months compared with gemcitabine (HR 0.57) [9], and gemcitabine + nab-paclitaxel achieved a median OS of 8.5 vs 6.7 months in MPACT (HR 0.72) [10]. In NAPOLI-3 (770 patients), the NALIRIFOX regimen (liposomal irinotecan + oxaliplatin + leucovorin + fluorouracil) was superior to gemcitabine + nab-paclitaxel: median OS 11.1 vs 9.2 months (HR 0.83; CI 0.70–0.99), with similar rates of grade ≥3 adverse events (87% vs 86%) [11]. NALIRIFOX has not been compared head-to-head with FOLFIRINOX [19]. The 2025 update of the ESMO guideline recommends FOLFIRINOX or NALIRIFOX for patients with ECOG performance status 0–1 [I, A] and also considers gemcitabine + nab-paclitaxel an appropriate option [I, B]; in the second line after FOLFIRINOX, gemcitabine + paclitaxel [I, B], or gemcitabine + nab-paclitaxel or gemcitabine alone [III, C], is suggested [19].
gBRCA and olaparib
In the POLO trial, patients with a germline BRCA1/2 mutation whose disease had not progressed during first-line platinum-based chemotherapy had a median PFS of 7.4 vs 3.8 months with maintenance olaparib (HR 0.53); in the final analysis, the OS difference was not statistically significant (median 19.0 vs 19.2 months; HR 0.83), although 3-year survival was estimated at 33.9% vs 17.8% [18]. Of 3315 patients screened, only 154 were randomized, showing that this subgroup is small [12].
Daraxonrasib: trials and place in guidelines
Daraxonrasib (RMC-6236) inhibits the active (GTP-bound) form of the RAS protein, whether mutant or wild-type [13]. In a phase 1–2 trial, among 26 patients with a RAS G12 mutation who received the drug second-line at a dose of 300 mg, the objective response rate was 35% [14]. In the randomized phase 3 RASolute 302 trial of 500 patients with previously treated metastatic pancreatic cancer, daraxonrasib increased median OS from 6.7 to 13.2 months (HR 0.40) and median PFS from 3.6 to 7.2 months (HR 0.49) compared with physician’s choice chemotherapy; this benefit was seen both in patients with a RAS G12 mutation and in the overall study population (including patients without an identified RAS mutation) [13]. Grade 3 or higher adverse events occurred in 61.8% of the daraxonrasib group and 69.6% of the chemotherapy group, and discontinuation due to treatment-related adverse events was 1.2% vs 11.2% [13].
The FDA approval of August 26, 2026 (brand name RASONQUE) specifies a dose of 300 mg orally once daily [28]. The ESMO guideline (rapid update, August 2026) recommends single-agent daraxonrasib after disease progression on chemotherapy in patients with a RAS G12 mutation and ECOG performance status 0 or 1, and considers the evidence insufficient in patients without a RAS mutation or with other RAS mutations [20]; NCCN has also added it as a subsequent-line therapy [4].
mRNA vaccine: study design and follow-up
In the phase 1 trial of autogene cevumeran, after surgery 16 patients first received atezolizumab and the vaccine, and 15 of them then received mFOLFIRINOX; the vaccine induced a strong tumor-specific T-cell response in 8 of 16 patients [15]. At a median follow-up of 3.2 years, median recurrence-free survival had not been reached in vaccine responders, compared with 13.4 months in non-responders [16].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index11 regimens
- Fluorouracil or capecitabine (FOLFIRINOX, mFOLFIRINOX, NALIRIFOX, NAPOLI-1, gemcitabine + capecitabine): testing for DPYD gene variants is recommended before starting (risk of severe toxicity with DPD deficiency) [31, 23].
- Conventional irinotecan (FOLFIRINOX and mFOLFIRINOX): in UGT1A1*28 or *6 homozygotes (or *6/*28), reduce the starting dose by at least one level; treat late diarrhea promptly with loperamide and early cholinergic diarrhea with atropine; antiemetic premedication is recommended [30].
- Liposomal irinotecan (NALIRIFOX and NAPOLI-1): not interchangeable with conventional irinotecan; give a corticosteroid and an antiemetic 30 minutes before each dose; there is no recommended dose for bilirubin above the upper limit of normal [25].
For physicians
Adjuvant (postoperative) and neoadjuvant (preoperative) therapy
Adjuvant mFOLFIRINOX (PRODIGE 24)
Resected pancreatic ductal adenocarcinoma (R0 or R1); age 18 to 79 years; WHO performance status 0–1; postoperative CA19-9 at most 180 U/mL; start 21 to 84 days after surgeryCycle length: Every 14 days
Resected pancreatic ductal adenocarcinoma (R0 or R1); age 18 to 79 years; WHO performance status 0–1; postoperative CA19-9 at most 180 U/mL; start 21 to 84 days after surgery
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 hours | Day 1 |
| Irinotecan | 150 mg/m² | IV over 90 minutes | Day 1 |
| Leucovorin | 400 mg/m² | IV over 2 hours | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² (no bolus) | IV, 46-hour continuous infusion | Starting Day 1 |
Doses from the PRODIGE 24 publication (the irinotecan dose was reduced from 180 to 150 mg/m² after a protocol-specified safety analysis) [6]; infusion durations, the absence of a fluorouracil bolus and the eligibility criteria from the trial registration [29]. Survival evidence: PRODIGE 24, 5-year follow-up [17].
Evidence: PRODIGE 24 (2022), PRODIGE 24 / CCTG PA.6 (2018)
Gemcitabine + capecitabine (ESPAC-4)
Resected pancreatic adenocarcinoma (R0 or R1) in patients unfit for mFOLFIRINOX; in the trial, started within 12 weeks after surgeryCycle length: Every 28 days
Resected pancreatic adenocarcinoma (R0 or R1) in patients unfit for mFOLFIRINOX; in the trial, started within 12 weeks after surgery
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Gemcitabine | 1000 mg/m² | IV over 30 minutes | Days 1, 8 and 15 |
| Capecitabine | 830 mg/m² twice daily (1660 mg/m² per day) | Oral | Days 1–21 |
Doses from ESPAC-4 [7] and the capecitabine FDA label (maximum of 6 cycles) [23].
Capecitabine: reduce the dose by 25% for creatinine clearance 30 to 50 mL/min; no dose has been established below 30 mL/min; do not use in complete DPD deficiency [23].
Evidence: ESPAC-4 (2017)
Neoadjuvant FOLFIRINOX (PREOPANC-2)
Resectable or borderline resectable pancreatic cancer; WHO performance status 0–1Cycle length: Every 14 days
Resectable or borderline resectable pancreatic cancer; WHO performance status 0–1
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 hours | Day 1 |
| Irinotecan | 180 mg/m² | IV over 90 minutes | Day 1 |
| Leucovorin | 400 mg/m² | IV over 2 hours | Day 1 |
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² | IV, 46-hour continuous infusion | Starting Day 1 |
Doses and schedule from PREOPANC-2 [21]; infusion durations per the FDA labels [32, 30]. In resectable disease without high-risk features, the benefit of neoadjuvant therapy has not been established [4, 22].
Evidence: PREOPANC-2 (2025), NORPACT-1 (2024)
Neoadjuvant gemcitabine-based chemoradiotherapy (PREOPANC)
Resectable or borderline resectable pancreatic cancerCycle length: Every 28 days
Resectable or borderline resectable pancreatic cancer
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Preoperative: 3 cycles of 28 days | |||
| Gemcitabine | 1000 mg/m² | IV | Cycles 1 and 3: Days 1 and 8; Cycle 2: Days 1, 8 and 15 |
| Hypofractionated radiotherapy | 36 Gy in 15 fractions | External beam | During cycle 2 only |
| Postoperative: 4 cycles | |||
| Adjuvant gemcitabine | IV | ||
Doses and schedule from PREOPANC-2 (chemoradiotherapy arm) [21]; survival evidence compared with upfront surgery: PREOPANC [8].
Evidence: PREOPANC-2 (2025), PREOPANC (2022)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Metastatic disease: first-line, maintenance and later lines
FOLFIRINOX (ACCORD 11)
First-line metastatic disease; ECOG 0–1Cycle length: Every 14 days
First-line metastatic disease; ECOG 0–1
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 hours | Day 1 |
| Irinotecan | 180 mg/m² | IV over 90 minutes | Day 1 |
| Leucovorin | 400 mg/m² | IV over 2 hours | Day 1 |
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² | IV, 46-hour continuous infusion | Starting Day 1 |
Doses from ACCORD 11 [9]; infusion durations of oxaliplatin and leucovorin (120 minutes) and irinotecan (90 minutes) per the FDA labels [32, 30].
Evidence: PRODIGE 4 / ACCORD 11 (2011)
NALIRIFOX (NAPOLI-3)
First-line metastatic disease; ECOG 0–1; bilirubin within the normal rangeCycle length: Every 28 days
First-line metastatic disease; ECOG 0–1; bilirubin within the normal range
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Liposomal irinotecan | 50 mg/m² | IV over 90 minutes | Days 1 and 15 |
| Oxaliplatin | 60 mg/m² | IV over 120 minutes | Days 1 and 15 |
| Leucovorin | 400 mg/m² | IV over 30 minutes | Days 1 and 15 |
| Fluorouracil | 2400 mg/m² | IV, 46-hour continuous infusion | Days 1 and 15 |
Evidence: NAPOLI 3 (2023)
Gemcitabine + nab-paclitaxel (MPACT)
First-line metastatic disease (in MPACT, Karnofsky ≥70); or second-line after FOLFIRINOXCycle length: Every 28 days
First-line metastatic disease (in MPACT, Karnofsky ≥70); or second-line after FOLFIRINOX
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nab-paclitaxel | 125 mg/m² | IV over 30 to 40 minutes | Days 1, 8 and 15 |
| Gemcitabine (immediately after nab-paclitaxel) | 1000 mg/m² | IV over 30 minutes | Days 1, 8 and 15 |
Doses from the nab-paclitaxel FDA label and MPACT [24, 10].
Do not administer if the neutrophil count is below 1500/µL, and frequent blood counts are required; not recommended in pancreatic cancer with moderate to severe hepatic impairment; peripheral neuropathy may require dose reduction [24].
Evidence: MPACT (2013)
Maintenance olaparib (POLO)
Germline BRCA1/2 mutation and metastatic disease that has not progressed during at least 16 weeks of first-line platinum-based chemotherapyCycle length: Continuous
Germline BRCA1/2 mutation and metastatic disease that has not progressed during at least 16 weeks of first-line platinum-based chemotherapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib (tablets) | 300 mg twice daily | Oral | Continuous |
Dose and indication from the FDA label [26] and POLO [12]. For creatinine clearance 31 to 50 mL/min, 200 mg twice daily [26].
Evidence: POLO (2022), POLO (2019)
Liposomal irinotecan + fluorouracil/leucovorin (NAPOLI-1)
Metastatic disease after progression on gemcitabine-based therapyCycle length: Every 14 days
Metastatic disease after progression on gemcitabine-based therapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Liposomal irinotecan | 70 mg/m² (UGT1A1*28 homozygous: start at 50 mg/m²) | IV over 90 minutes | Day 1 |
| Leucovorin | 400 mg/m² | IV over 30 minutes | Day 1 |
| Fluorouracil | 2400 mg/m² | IV over 46 hours | Day 1 |
Single-agent gemcitabine
Advanced disease in patients with poorer performance status, or second-line after FOLFIRINOX
Advanced disease in patients with poorer performance status, or second-line after FOLFIRINOX
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Gemcitabine | 1000 mg/m² | IV over 30 minutes | Weekly for 7 weeks, then 1 week of rest; then Days 1, 8 and 15 |
Dose from the gemcitabine FDA label [27].
Daraxonrasib (RASolute 302)
Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients unfit for multiagent therapy (FDA label); ESMO: RAS G12 mutation and ECOG 0–1Cycle length: Continuous
Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or patients unfit for multiagent therapy (FDA label); ESMO: RAS G12 mutation and ECOG 0–1 [20]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Daraxonrasib | 300 mg once daily | Oral | Continuous |
Dose from the FDA label [28]; evidence: RASolute 302 [13].
Skin toxicity prevention from the start of treatment: a topical corticosteroid and a moisturizing cream on the face and chest, limiting sun exposure and using sunscreen with SPF 30 or higher, and considering prophylactic oral doxycycline or minocycline. Dose reduction to 200 mg, then to 150 mg; discontinue if 150 mg is not tolerated; grade 3 rash, stomatitis or diarrhea → withhold until grade ≤1, then resume at a lower dose [28].
Evidence: RASolute 302 (2026), RASolute 302 (2026), RASolute-302 (2026)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Scientific evidence
Key studies
15 itemsFive-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial
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
Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial
Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial
Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer
NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial
Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
RNA neoantigen vaccines prime long-lived CD8(+) T cells in pancreatic cancer
FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
Clinical guidelines
4 itemsPancreatic Adenocarcinoma, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
ESMO Clinical Practice Guideline Express Update on the management of metastatic pancreatic cancer
Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Metastatic Pancreatic Cancer: ASCO Guideline Update
References
32 referencesShow all references, 21 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer
- 15
- 16
- 17
- 18Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer
- 19
- 20
- 21
- 22Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial
- 23
- 24
- 25
- 26
- 27Gemcitabine injection, for intravenous use — Prescribing Information
- 28
- 29Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma (PRODIGE 24/CCTG PA.6; NCT01526135)
- 30
- 31Fluorouracil injection, for intravenous use — Prescribing Information
- 32
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.