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Every dated change on the records linked to Pancreatic ductal adenocarcinoma, newest first: approvals and regulatory steps on its medicines, trials that reported, guideline versions, milestones, and when this page itself was checked. Dates come from the records; none is inferred. Orientation, not medical advice.
Metastatic pancreatic adenocarcinoma after at least one prior systemic therapy, or in adults who are not candidates for multiagent systemic therapy
Locally advanced pancreatic cancer with chemotherapy
Primary DFS endpoint not met.
OS 13.
Second-line daraxonrasib 300 mg in 26 patients with RAS G12-mutated pancreatic cancer: objective response 35 percent, median progression-free survival 8.
FUT3-null patients, about 10%, have median CA 19-9 of 2.4 U/mL and the same short survival as patients above 200; a value of 7 or below identifies them without genotyping.
ASCO plenary and NEJM; FDA approval of daraxonrasib on 26 August 2026; Optune Pax approved; zoldonrasib combinations reported; AMPLIFY-7P vaccine misses.
Objective response 30 percent across 158 evaluable NRG1 fusion-positive cancers, 42 percent (15 of 36) in pancreatic cancer; median duration of response 11.
Overall survival longer with elraglusib in a randomised phase 2; confirmation pending.
Overall R0 resection rate 25 percent with chemoradiotherapy against 18 percent with chemotherapy (p 0.
OS 16.
Median overall survival 21.
Tumour treating fields with gemcitabine and nab-paclitaxel: 16.2 against 14.2 months in 571 patients with locally advanced disease.
Neoadjuvant FOLFIRINOX 21.9 versus 21.3 months against gemcitabine chemoradiotherapy. Sethna: responders' recurrence-free survival not reached at 3.2 years.
Liposomal irinotecan in NALIRIFOX first-line metastatic pancreatic cancer
First-line metastatic pancreatic adenocarcinoma in NALIRIFOX (NAPOLI 3)
First-line metastatic pancreatic adenocarcinoma
NRG1-fusion NSCLC and pancreatic adenocarcinoma
No overall survival benefit from adding devimistat to modified FOLFIRINOX.
Median overall survival 16.
Primary overall survival endpoint not met.
Alive at 18 months: 60 percent with neoadjuvant FOLFIRINOX against 73 percent with upfront surgery (p 0.
Placebo-adjusted weight gain 2.
A milestone in how this cancer is treated.
Mismatch repair deficient or MSI-high tumours: NICE TA914 (20 September 2023) covers previously treated endometrial, gastric, small intestine, biliary and colorectal cancer and does not include pancreatic cancer
Upfront pancreatoduodenectomy or distal pancreatectomy followed by six months of adjuvant chemotherapy remains the reference for clearly resectable tumours: NORPACT-1 found 18-month survival 60 percent with neoadjuvant FOLFIRINOX against 73 percent with surgery first, SWOG S1505 found two-year survival of 47 to 48 percent with either perioperative regimen (no better than adjuvant history), and NEONAX missed its 18-month disease-free target in both arms. In favour of treating first: PREOPANC-1's neoadjuvant gemcitabine chemoradiotherapy gave five-year survival 20.5 against 6.5 percent (hazard ratio 0.73) across resectable and borderline patients, and PREOPANC-2 found neoadjuvant FOLFIRINOX and neoadjuvant chemoradiotherapy equivalent (21.9 against 21.3 months). Alliance A021806 (358 patients, perioperative against adjuvant modified FOLFIRINOX, primary completion December 2028) and PREOPANC-3 (378 patients) will settle the question; NICE NG85 restricts neoadjuvant therapy to trials (1.8.1, 1.8.2). (NCCN Category 1 (adjuvant chemotherapy); Category 2A (neoadjuvant for high-risk features))
Neoadjuvant chemotherapy for two to four months, then restaging and surgery: ESPAC-5 (90 patients, UK and Germany) found one-year survival 39 percent with immediate surgery against 78 percent after gemcitabine plus capecitabine, 84 percent after FOLFIRINOX and 60 percent after chemoradiotherapy. Alliance A021501 established modified FOLFIRINOX alone as the reference regimen (18-month survival 66.7 percent, median 29.8 months) after its stereotactic radiotherapy arm closed at interim analysis for fewer R0 resections (10 against 17 of the first 30). PREOPANC-1 and PREOPANC-2 included borderline patients with the same conclusions as above. NICE NG85 still asks for neoadjuvant therapy to be given within a trial (1.8.1). (NCCN Category 2A (neoadjuvant therapy preferred))
Opioid analgesia with endoscopic ultrasound-guided or percutaneous coeliac plexus block for uncontrolled pain, opioid side effects or escalating doses (NG85 1.5.1; Wyse 2011 randomised trial: pain scores lower at three months, no survival effect); no thoracic splanchnicectomy (1.5.2). Enteric-coated pancreatin with every meal for everyone with unresectable disease and around surgery (1.6.1, 1.6.2); no fish oils for weight loss (1.6.3); early enteral rather than parenteral nutrition after pancreatoduodenectomy (1.6.4). Dietetic review and early palliative care from diagnosis. Cachexia drugs are in trials (ponsegromab, seven UK sites). Thromboprophylaxis is decided by risk score under the NICE venous thromboembolism guideline; in CASSINI's pancreatic subgroup rivaroxaban cut clots during treatment (3.7 against 10.1 percent) but not over 180 days.
Self-expanding metal stent by ERCP for jaundice in unresectable disease and, when drainage is needed before surgery, in resectable disease (NG85 1.7.3 to 1.7.5); metal stents stay open 4.45 months longer than plastic with fewer cholangitis episodes and re-interventions (Almadi 2017, 20 trials). Endoscopic ultrasound-guided drainage when ERCP fails or is expected to be difficult (Paik 2018; DRA-MBO 2023). Surgery first rather than preoperative drainage in fit resectable patients (1.7.1). For duodenal obstruction, an enteral stent relieves symptoms within days and gastrojejunostomy lasts longer (SUSTENT); choose bypass for people with a better prognosis (1.7.8) and consider prophylactic gastrojejunostomy when a tumour is found unresectable at operation (1.7.6).
Modified FOLFIRINOX for six months in fit patients (PRODIGE 24: median overall survival 53.5 against 35.5 months with gemcitabine, hazard ratio 0.68, five-year survival 43.2 against 31.4 percent). Gemcitabine plus capecitabine for those not eligible (ESPAC-4: 28.0 against 25.5 months, hazard ratio 0.82; long-term 31.6 against 28.4 months, and 49.9 against 32.2 months after R0 resection); this is the NICE NG85 recommendation for England (1.8.6, off-label). Gemcitabine alone for the frail (CONKO-001: five-year survival 20.7 against 10.4 percent with observation; NG85 1.8.7). S-1 for six months in Japan (JASPAC 01: five-year survival 44.1 against 24.4 percent with gemcitabine, hazard ratio 0.57), not licensed for this use in Europe. Nab-paclitaxel with gemcitabine missed its primary endpoint (APACT) and is not a standard. Start within 12 weeks of surgery once recovered. (NCCN Category 1, preferred (mFOLFIRINOX); Category 1 (gemcitabine plus capecitabine, gemcitabine), ESMO-MCBS A (PRODIGE 24))
Four to six months of modified FOLFIRINOX or gemcitabine plus nab-paclitaxel (NEOLAP: conversion to resection in 36 to 44 percent of randomised patients with either sequence, median survival 18.5 to 20.7 months). Chemoradiotherapy after induction improves local control but not survival: LAP07 (15.2 against 16.5 months; local progression 32 against 46 percent), CONKO-007 (R0 resection 25 against 18 percent overall, not significant; 69 against 50 percent among those operated; survival hazard ratio 0.94). When it is used, capecitabine is the radiosensitiser (SCALOP: median survival 15.2 against 13.4 months with gemcitabine; NG85 1.9.3). Stereotactic radiotherapy and irreversible electroporation are options in centres with experience: CROSSFIRE (68 patients after FOLFIRINOX) found MRI-guided stereotactic radiotherapy and electroporation equivalent (16.1 against 12.5 months, hazard ratio 1.39, stopped for futility), and PANFIRE-2 (50 patients) reported median survival 17 months from diagnosis with major complications in 42 percent. Tumour treating fields added to gemcitabine plus nab-paclitaxel are approved in the United States (PANOVA-3). (NCCN Category 2A (induction chemotherapy; chemoradiation or SBRT in selected patients))
FOLFIRINOX for performance status 0 to 1 (PRODIGE 4/ACCORD 11: median overall survival 11.1 against 6.8 months with gemcitabine, hazard ratio 0.57; febrile neutropenia 5.4 percent) or NALIRIFOX (NAPOLI 3: 11.1 against 9.2 months with nab-paclitaxel and gemcitabine, hazard ratio 0.83 in the Lancet report and 0.84 on the Onivyde label; FDA approval 13 February 2024, EU indication listed; NICE appraisal TA1052 terminated on 2 April 2025 without a company submission). Gemcitabine plus nab-paclitaxel for those less fit or with biliary stents (MPACT: 8.5 against 6.7 months, hazard ratio 0.72; grade 3 or worse neuropathy 17 percent); in England only when other combinations are unsuitable (NICE TA476). Gemcitabine alone for the frail. Four months of FOLFIRINOX then fluorouracil and leucovorin maintenance is an alternative to six months (PANOPTIMOX-PRODIGE 35: six-month progression-free survival 42.9 against 47.1 percent, survival without quality-of-life deterioration 11.4 against 7.2 months). Germline and tumour testing at diagnosis (BRCA, PALB2, mismatch repair, KRAS subtype, NRG1 and NTRK fusions) steers maintenance and later lines. (NCCN Category 1, preferred (FOLFIRINOX, NALIRIFOX, gemcitabine plus nab-paclitaxel), ESMO-MCBS 5 (PRODIGE 4); 3 (MPACT); 3 (NAPOLI 3))
Independently assessed disease-free survival 19.
Vaccine-induced T cells in 8 of 16 patients; median recurrence-free survival not reached in responders against 13.
Median overall survival 11.
Objective response 21 percent (8 of 38; 95 percent confidence interval 10 to 37); median progression-free survival 4.
One-year overall survival 39 percent with immediate surgery against 78 percent with neoadjuvant gemcitabine plus capecitabine, 84 percent with FOLFIRINOX and 60 percent with chemoradiotherapy (p 0.
Weight gain over 5%: 60% vs 9%; appetite improvement 43% vs 13%.
OS HR 0.
18-month disease-free survival 33.
Overall survival improved with nimotuzumab plus gemcitabine in KRAS wild-type disease.
Pancreatic cancer cohort: objective response in 7 of 21 patients (33.
A milestone in how this cancer is treated.
18-month overall survival 66.
5-year OS 20.
PFS HR 0.
1,461 high-risk people enrolled; across CAPS1 to 5 (1,731 people) 57.9 percent of the 19 surveillance-detected cancers were stage I, with five-year survival 73.3 percent and median overall survival 9.8 years against 1.5 years for cancers found outside surveillance.
Adjuvant modified FOLFIRINOX against gemcitabine: median overall survival 53.5 versus 35.5 months, five-year survival 43.2 versus 31.4 percent, hazard ratio 0.68.
Surgical conversion 35.
Six-month progression-free survival 47.
Median overall survival 9.
Two-year overall survival 47 percent with perioperative modified FOLFIRINOX and 48 percent with perioperative gemcitabine plus nab-paclitaxel; neither exceeded the 40 percent historical threshold; median overall survival 23.
Primary overall survival endpoint not met.
Only 1-2% of pancreatic cancers carry G12C, but the door is open.
Reactive and deserted tissue states track immunity and chemoprotection; CA 19-9 rises two years before diagnosis, reaching 60% sensitivity only in the last six months.
Maintenance treatment of germline BRCA1/2-mutated metastatic pancreatic adenocarcinoma that has not progressed after at least 16 weeks of platinum-based first-line chemotherapy; listed in the EMA Lynparza product information read on 24 September 2026 (extension of indication in 2020)
Olaparib 300 mg twice daily for people with a germline BRCA1 or BRCA2 mutation whose metastatic disease has not progressed after at least 16 weeks of platinum chemotherapy (POLO: progression-free survival 7.4 against 3.8 months, hazard ratio 0.53; overall survival 19.0 against 19.2 months, hazard ratio 0.83, not significant; three-year survival 33.9 against 17.8 percent; FDA approval 2019, EU indication listed; NICE appraisal TA750 terminated on 8 December 2021 without a company submission). Continued chemotherapy, or fluorouracil and leucovorin maintenance after FOLFIRINOX (PANOPTIMOX), are the alternatives for everyone else. About 2 to 3 percent of unselected patients carry a germline BRCA1 or BRCA2 variant (Hu 2018, 3,030 patients: BRCA2 1.9 percent, BRCA1 0.6 percent), more in familial disease; 7.5 percent of the 3,315 screened for POLO carried one and 154 were randomised. (NCCN Category 1 (olaparib, germline BRCA), ESMO-MCBS 3 (POLO))
RAS: daraxonrasib works across RAS G12 mutations (91.8 percent of RASolute 302) and is approved regardless of subtype; KRAS G12C (1 to 2 percent of tumours) responds to sotorasib (CodeBreaK 100 pancreatic cohort, 38 patients: response 21 percent, median survival 6.9 months) and adagrasib (KRYSTAL-1: 7 of 21 responses), which NCCN lists but no regulator has approved for pancreatic cancer; KRAS G12D (about 40 percent) has zoldonrasib in phase 3 first line (RASolute 305 with chemotherapy, RASolute 309 with daraxonrasib) after MRTX1133 was stopped. NRG1 fusions (KRAS wild-type tumours): zenocutuzumab (eNRGy: response 42 percent in 36 pancreatic patients; FDA accelerated approval 4 December 2024; not authorised in the EU). Mismatch repair deficiency (about 1 percent): pembrolizumab (KEYNOTE-158 pancreatic cohort: 4 of 22 responses, 18 percent) or dostarlimab under tumour-agnostic US approvals; NICE TA914 does not cover pancreatic cancer. NTRK fusions: larotrectinib (NICE TA630, Cancer Drugs Fund) or entrectinib (TA644 replaced by the terminated TA1118); repotrectinib after resistance. BRAF V600E: dabrafenib plus trametinib. Erlotinib with gemcitabine is licensed for metastatic disease in the US and EU but added under two weeks in its pivotal trial and nothing in later trials, and is not used. (NCCN Category 2A (sotorasib, adagrasib for G12C; zenocutuzumab for NRG1; pembrolizumab or dostarlimab for dMMR; larotrectinib or entrectinib for NTRK))
Daraxonrasib after one prior line (RASolute 302: median overall survival 13.2 against 6.7 months with chemotherapy, hazard ratio 0.40; progression-free 7.2 against 3.6 months; FDA approval 26 August 2026 for metastatic pancreatic adenocarcinoma after one systemic therapy or for people not fit for multi-agent chemotherapy; no EU or UK decision). Otherwise switch backbone: after gemcitabine, liposomal irinotecan with fluorouracil and leucovorin (NAPOLI-1: 6.1 against 4.2 months, hazard ratio 0.67; FDA 2015, EU 2016, not recommended by NICE TA440) or OFF (CONKO-003: 5.9 against 3.3 months, hazard ratio 0.66), noting that PANCREOX found modified FOLFOX6 worse than fluorouracil alone; after FOLFIRINOX, gemcitabine plus nab-paclitaxel. NG85 recommends oxaliplatin-based or gemcitabine-based second line (1.9.7, 1.9.8). Pegilodecakin (SEQUOIA) and eryaspase (TRYbeCA-1) failed here. (NCCN Category 1 (daraxonrasib; liposomal irinotecan with fluorouracil after gemcitabine); Category 2A (OFF, FOLFOX), ESMO-MCBS 2 (NAPOLI-1))
Most people with pancreatic cancer lose appetite and weight (Cancer Research UK), and the loss has two parts: undigested food, which enzymes fix, and the cancer's own effect on appetite and muscle (cachexia), which needs a dietitian early. Cancer Research UK says most pancreatic teams include a dietitian, and its advice is small frequent meals, high-calorie and high-protein snacks and full-fat versions, prescribed supplement drinks sipped through the day (with enzymes, and checked against diabetes), and eating what you feel like rather than what you think you should. Pancreatic Cancer UK says there is no special diet and no foods to avoid, and not to cut fat but to take more PERT with it. Medicines for appetite: Macmillan says steroids or an appetite stimulant may help for a time; the ASCO cachexia guideline recommends dietary counselling and says no drug is established. NICE NG85 says do not offer fish oils to manage weight loss in unresectable disease, and after a Whipple operation to offer early feeding by mouth or tube rather than into a vein when the gut works. With a duodenal stent: soft, moist, lower-fibre foods, little and often, chewed well, upright after eating. Weight and muscle are also what decide whether chemotherapy can be given on time and in full, so ask for the referral in the first weeks, not when the weight has gone.
Median overall survival 11.
Biliary cohort ORR 5.
Median overall survival 17 months from diagnosis (95 percent confidence interval 15 to 19) and 10 months from electroporation in locally advanced disease; local recurrence 46 percent; major complications in 21 events across 29 of 50 participants.
Goal: high-grade dysplasia and T1N0M0 cancer; EUS and MRI/MRCP yearly; ATM carriers with an affected relative now eligible.
Core and biallelic repair-gene mutations predict first-line platinum benefit (hazard ratio 0.44); single-cell sequencing adds antigen-presenting fibroblasts to the myofibroblastic and inflammatory states.
Preoperative chemoradiotherapy: 16.0 versus 14.3 months, R0 71 versus 40 percent. Pegvorhyaluronidase: 11.2 versus 11.5 months. Germline and tumour testing for every treatment-eligible patient.
Olaparib maintenance in germline BRCA-mutated metastatic pancreatic cancer
Maintenance treatment of deleterious or suspected deleterious germline BRCA-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of first-line platinum-based chemotherapy (POLO), with an FDA-approved companion diagnostic
Median overall survival 3.
PFS HR 0.
Classical tumours respond to chemotherapy three times as often as basal-like; 3,594 profiled tumours give KRAS 88% and MSI or TMB-high 0.5%; a CLIA KRAS ctDNA assay predicts recurrence 84 days before imaging.
First biomarker-directed approval.
Adenosquamous, colloid and undifferentiated carcinomas and the IPMN- and MCN-associated carcinomas listed as variants of ductal adenocarcinoma; solid pseudopapillary neoplasm and acinar cell carcinoma stand apart.
About one in five pancreatic cancers can be removed at diagnosis (the OnCo record; Pancreatic Cancer UK says only a small number of people can have surgery), and the word the multidisciplinary team gives you decides the order. Resectable (no contact with the main arteries, no more than abutment of the veins, no spread): NICE NG85 says surgery first, and only consider chemotherapy before surgery within a clinical trial; the operation is usually a Whipple procedure for the head of the pancreas or a distal pancreatectomy for the body and tail, followed by six months of chemotherapy. Borderline resectable (the tumour touches a main vein or artery, so an operation straight away would probably leave cancer behind): chemotherapy first for two to four months, usually modified FOLFIRINOX, then restaging, with surgery about 6 to 8 weeks after chemotherapy if the disease has not spread; NICE NG85 also places this within a trial, and Cancer Research UK says your doctor may offer one because the best treatment is uncertain. In the Dutch PREOPANC trial, chemoradiotherapy before surgery improved five-year survival over surgery first (20.5% against 6.5%), most clearly for borderline disease; the record's open problems note the question is unresolved for resectable disease after PREOPANC-2, NORPACT-1 and Alliance A021806. Fitness matters as much as anatomy: only people well enough for a major operation are offered one, prehabilitation (exercise, nutrition, stopping smoking) is offered in some hospitals, and if jaundice needs relieving first a metal stent is placed. A second opinion from a specialist pancreatic centre is reasonable when the scan is read differently by different teams.
Pancreatic protocol CT of chest, abdomen and pelvis before any biliary drainage; FDG PET-CT for localised disease before treatment; EUS with tissue sampling when a diagnosis or node staging is needed; MRI for suspected liver metastases and laparoscopy with laparoscopic ultrasound before an attempted resection when small-volume spread is suspected; CA 19-9 at baseline; germline testing for every patient; decision by a specialist pancreatic multidisciplinary team.
Enteric-coated pancreatin for everyone with unresectable disease and consideration before and after resection; early enteral rather than parenteral nutrition after pancreatoduodenectomy; no fish oils for weight loss in unresectable disease; dietitian assessment for the weight loss, malabsorption and cachexia that affect most patients.
OS 54.
Median OS 54 months after resection.
Hu, 3,030 patients. Canto, 354 high-risk individuals over 16 years: 9 of 10 surveillance-detected cancers resectable. Sharma's ENDPAC score for new-onset diabetes.
Pancreatic protocol CT before biliary drainage, PET-CT for localised disease, enzyme replacement for unresectable disease, surveillance criteria for inherited risk.
NRG1 fusions found in every KRAS wild-type tumour of a young-adult series (Heining), later put at about 1% of all pancreatic cancers (Philip 2022); only 3 of 33 Johns Hopkins germline carriers had a family history (Shindo). The 5.5% carrier rate of Hu 2018 is on the evidence entry for the same year.
Median disease-free survival 11.
Median overall survival 28.
Survivors have both many high-quality neoantigens and abundant CD8 T cells, and lose those clones at metastasis; TCGA fixes the driver list and shows KRAS wild-type tumours carry other RAS-pathway drivers.
T1 to T3 by size (2 and 4 cm), N1 and N2 by one to three and four or more nodes; validated in 2,318 resections from three US centres and 8,960 SEER cases.
Metastatic pancreatic adenocarcinoma after gemcitabine, with fluorouracil and leucovorin
No overall survival benefit.
Five-year overall survival 44.
Median overall survival 15.
Median overall survival 6.
456 tumours, 32 genes, 10 pathways, squamous subtype worst. Liposomal irinotecan with fluorouracil: 6.1 versus 4.2 months after gemcitabine.
Notta's whole genomes show chromothripsis and polyploidy, not stepwise mutation, in two-thirds of tumours, knocking out several drivers at once; Bailey's four expression subtypes from the same year are on the evidence entry.
Liposomal irinotecan with 5-FU/LV in metastatic pancreatic cancer after gemcitabine
Metastatic pancreatic adenocarcinoma after gemcitabine-based therapy, with fluorouracil and leucovorin (NAPOLI-1)
CE mark (GBM); pancreatic and NSCLC CE marks 2024-26
PanIN, IPMN and MCN move to a two-tier grading; 0.5 to 1 cm separates a large PanIN from an incipient IPMN.
Waddell's 100 genomes tie unstable genomes to BRCA-type defects and platinum response; Moffitt separates tumour from stroma and finds two tumour and two stromal subtypes; Witkiewicz's 109 microdissected exomes give the purified driver frequencies.
First-line metastatic pancreatic adenocarcinoma (nab-paclitaxel label)
First-line metastatic pancreatic adenocarcinoma with gemcitabine (MPACT)
Median disease-free survival 13.
Median overall survival 8.
Nine-month progression-free survival 62.
A milestone in how this cancer is treated.
Metastatic PDAC (PRODIGE 4 / ACCORD 11; component drugs generic)
Median overall survival 11.
PRODIGE 4 / ACCORD 11 establishes combination chemotherapy for fit patients.
GNAS R201 in 66% of IPMNs and carried into the invasive cancer; Collisson's classical, quasi-mesenchymal and exocrine-like classes.
Median overall survival 23.
A decade from the initiating mutation to the founder clone and five more years to metastatic ability: the quantitative case for early detection.
Metastatic breast cancer; later pancreatic (2013) and non-small-cell lung cancer (2015)
Twenty-four cancers carried an average of 63 alterations hitting twelve pathways in 67 to 100% of tumours.
Metastatic pancreatic cancer with gemcitabine (Tarceva product information: factors associated with prolonged survival should be taken into account when prescribing; 100 mg daily); marketing authorisation for the product 19 September 2005
368 patients; 13.4 versus 6.9 months.
Pancreatic cancer with gemcitabine
Chari's Minnesota cohort of 2,122; observed-to-expected ratio 7.94.
Five-year survival 21 percent with adjuvant chemotherapy against 8 percent without (p 0.
289 patients; five-year survival 21 versus 8 percent with chemotherapy, 10 versus 20 percent with chemoradiotherapy.
Pancreatic cancer: NICE TA25 (8 May 2001), since replaced by the NG85 guideline, which recommends gemcitabine alone for people not well enough for combination chemotherapy (1.9.6) and as adjuvant treatment for those who cannot tolerate gemcitabine plus capecitabine (1.8.7)
Eight pathologists had used more than 70 terms for 35 duct lesions; the working group adopted pancreatic intraepithelial neoplasia grades 1 to 3, and precursor research became comparable.