Pancreatic Cancer Landmark Atlas

What did the researchers want to learn?

After pancreatic cancer surgery, does gemcitabine chemotherapy prolong the time before the disease comes back compared with observation alone?

What did this study change?

It became one of the key pieces of evidence supporting the role of drug treatment after pancreatic cancer surgery.

Benefit for patients

Relevant to patients with resected pancreatic adenocarcinoma.

What did the research find?

Postoperative gemcitabine clearly prolonged the time before the disease came back (median 13.4 months and 6.7 months). In the long-term analysis, a survival benefit was also reported (median 22.8 months and 20.2 months).

Who does this apply to?

More effective combination treatments are available today; the results cannot be applied one-to-one to today's standard regimens.

What did the researchers want to learn?

After pancreatic cancer surgery, is two-drug chemotherapy (gemcitabine + capecitabine) better than gemcitabine alone?

What did this study change?

It showed the benefit of postoperative combination treatment.

Benefit for patients

Relevant to patients with resected pancreatic cancer.

What did the research find?

In the first publication, median overall survival (OS) was 28.0 vs 25.5 months; at long-term follow-up 31.6 vs 28.4 months (different time points). GemCap (gemcitabine plus capecitabine) was not compared directly with mFOLFIRINOX.

Who does this apply to?

ESPAC-4 did not directly compare GemCap with modified FOLFIRINOX. Current choice is made according to the patient's condition and later studies.

What did the researchers want to learn?

In pancreatic cancer removed by surgery, does the four-drug regimen mFOLFIRINOX prolong survival compared with gemcitabine?

What did this study change?

In selected patients in good condition, adjuvant mFOLFIRINOX became a preferred option in many guidelines.

Benefit for patients

Relevant to surgically treated pancreatic cancer patients with suitable general condition.

What did the research find?

In the first publication, median overall survival (OS) was 54.4 vs 35.0 months; at long-term follow-up it was 53.5 vs 35.5 months (different time points). Disease-free survival (DFS) and OS both improved; the regimen is intensive and may not be suitable for every patient.

Who does this apply to?

Applies to patients with adequate general condition after surgery who meet the eligibility criteria. It is not generalized to metastatic / inoperable disease or to neoadjuvant borderline-resectable questions.

What did the researchers want to learn?

Is giving gemcitabine together with nab-paclitaxel after surgery better than gemcitabine alone?

What did this study change?

It showed that a negative primary endpoint and later analyses need to be interpreted separately; it cannot be said to have changed the routine standard.

Benefit for patients

Relevant to patients with resected pancreatic cancer.

What did the research find?

The primary disease-free survival (DFS) endpoint, based on independent assessment, was not met (19.4 vs 18.8 months). Later overall survival (OS) findings do not erase this primary result.

Who does this apply to?

When the primary endpoint is not met, the standard should not be set on the basis of secondary analyses. It cannot be compared directly with PRODIGE-24.

What did the researchers want to learn?

In operable or borderline operable pancreatic cancer, is gemcitabine-based chemoradiotherapy before surgery better than going straight to surgery?

What did this study change?

It supported the importance of preoperative treatment strategies.

Benefit for patients

Relevant to patients with borderline resectable pancreatic cancer.

What did the research find?

In the long term, an overall survival (OS) benefit in the overall population (hazard ratio [HR] 0.73; 5-year 20.5% vs 6.5%). In the borderline subgroup HR 0.67 (p=0.045); in the resectable subgroup HR 0.79 (p=0.23, not significant) — read separately.

Who does this apply to?

The PREOPANC protocol is not the same as all of today's neoadjuvant approaches; resectable is not the same as borderline.

What did the researchers want to learn?

In operable or borderline operable pancreatic cancer, is total FOLFIRINOX before surgery better than gemcitabine-based chemoradiotherapy?

What did this study change?

It showed that more intensive treatment on its own does not guarantee a better result.

Benefit for patients

Relevant to patients planned for neoadjuvant pancreatic cancer treatment.

What did the research find?

The primary overall survival (OS) superiority could not be shown (21.9 vs 21.3 months; hazard ratio [HR] 0.88; p=0.32; modified intention-to-treat [mITT] n=369). This does not mean that neoadjuvant treatment is unnecessary or that the two are equivalent in every situation.

Who does this apply to?

It has not been proven that FOLFIRINOX is equivalent to chemoradiotherapy in all situations or that neoadjuvant treatment is unnecessary. Strategies change together.

What did the researchers want to learn?

In pancreatic head cancer that can be operated on, is short-course FOLFIRINOX before surgery better than going straight to surgery?

What did this study change?

It emphasized that directly operable and borderline operable disease should not be managed in the same way.

Benefit for patients

Relevant to patients with resectable pancreatic cancer.

What did the research find?

The study did not show a survival advantage for preoperative treatment; in some analyses results favored upfront surgery (median 25.1 months and 38.5 months; proportion of patients alive at 18 months 60% and 73%).

Who does this apply to?

Treatment completion rates and the treatment sequence are important in interpreting the results. It is an early-phase (phase II) study; it does not set a definitive standard.

What did the researchers want to learn?

In borderline operable pancreatic cancer, how do different short-course treatments before surgery perform compared with upfront surgery?

What did this study change?

It is one of the pieces of evidence supporting the approach of drug treatment first in borderline operable disease.

Benefit for patients

Relevant to patients with borderline resectable pancreatic cancer.

What did the research find?

One-year survival findings favoring preoperative treatment strategies were reported. No definite superiority of one regimen among the treatment arms can be stated.

Who does this apply to?

Because of the small number of patients and the different treatment arms, it cannot be claimed that a particular regimen is superior.

What did the researchers want to learn?

Does adding short-course intensive radiotherapy to preoperative mFOLFIRINOX chemotherapy improve outcomes?

What did this study change?

It showed that adding radiotherapy in borderline operable disease does not automatically give a better result.

Benefit for patients

Relevant to patients with borderline resectable pancreatic cancer.

What did the research find?

The arm with radiotherapy added did not meet the prespecified efficacy criterion; the chemotherapy arm showed more favorable results.

Who does this apply to?

The early-phase (phase II) design, the early closure of the arm and patient selection must be taken into account; it does not set a definitive standard.

What did the researchers want to learn?

If the disease has not progressed after first chemotherapy, does chemoradiotherapy prolong survival compared with continuing chemotherapy?

What did this study change?

It showed that control of the tumor in the same area and survival are not the same outcome.

Benefit for patients

Relevant to patients with locally advanced pancreatic cancer.

What did the research find?

No significant advantage in survival could be shown (median about 15.2 months and around 16.5 months, no significant difference); that is, the main goal of the study was not met. Some benefits were reported in terms of control of the tumor in the same area.

Who does this apply to?

Regimens different from today's systemic treatments were used. It does not cover the same patient group as the preoperative studies conducted in operable disease.

What did the researchers want to learn?

In metastatic pancreatic cancer with an inherited BRCA gene alteration that has not progressed on platinum-containing chemotherapy, is olaparib maintenance treatment beneficial?

What did this study change?

It increased the importance of germline BRCA testing in treatment selection.

Benefit for patients

Relevant to platinum-responsive, gBRCA-mutated metastatic pancreatic cancer patients.

What did the research find?

The time before the disease progressed was prolonged (median 7.4 months and 3.8 months; hazard ratio 0.53). A survival advantage, however, could not be shown.

Who does this apply to?

Valid for a very selected genetic and clinical patient group; it cannot be compared with NAPOLI-3 because it has a different purpose.

What did the researchers want to learn?

In previously untreated metastatic pancreatic cancer, is NALIRIFOX chemotherapy better than gemcitabine plus nab-paclitaxel?

What did this study change?

It supported a new first-line combination option in metastatic pancreatic cancer.

Benefit for patients

Relevant to patients with metastatic pancreatic adenocarcinoma.

What did the research find?

Median overall survival (OS) 11.1 vs 9.2 months (hazard ratio [HR] 0.83); median progression-free survival (PFS) 7.4 vs 5.6 months. It is a metastatic first-line population; NALIRIFOX is not the same as mFOLFIRINOX.

Who does this apply to?

Belongs to the metastatic population; it is not generalized to adjuvant / neoadjuvant settings. NALIRIFOX is not the same regimen as modified FOLFIRINOX. It is not the same question as POLO.

What did the researchers want to learn?

In previously treated metastatic pancreatic cancer, does oral daraxonrasib improve survival and the time before the disease progresses compared with chemotherapy chosen by the doctor?

What did this study change?

It showed that RAS-targeted therapy can prolong survival in previously treated metastatic pancreatic cancer; approval was obtained in the United States for some groups.

Benefit for patients

Relevant to patients with certain RAS-mutated pancreatic cancers.

What did the research find?

Survival and progression-free time improved significantly both in the group with a RAS G12 mutation and in all patients. In all patients, median survival was 13.2 months and 6.7 months (hazard ratio 0.40), progression-free time was 7.2 months and 3.6 months (hazard ratio 0.49), and the tumor response rate was 31.6% and 11.2%.

Who does this apply to?

It is an open-label study (patient and doctor know the treatment); it was not conducted in operable disease and long-term follow-up is needed. It does not mean a cure or a replacement for surgery; licensing and access in Turkey must be checked separately.

What did the researchers want to learn?

In metastatic pancreatic cancer with loss of the MTAP gene and a RAS mutation, does the combination of vopimetostat and daraxonrasib have an effect on the tumor?

What did this study change?

It shows the potential of a dual-targeted approach in MTAP-deleted pancreatic cancer; it is not evidence of superiority over standard treatment or chemotherapy. Larger studies are planned.

Benefit for patients

Relevant to selected molecular-subgroup research patients.

What did the research find?

In 22 evaluable patients, a tumor response rate of 82% (18/22; all partial responses) and a disease control rate of 100% were reported. Median progression-free survival has not yet been reached. The 29 treated patients and the 22 evaluable patients should not be confused.

Who does this apply to?

Because of the small number of patients, the lack of a control group and the short follow-up, the results are early; no survival advantage has been shown. An 82% response does not mean an 82% cure, and it should not yet be presented as standard treatment.