the pancreatic cancer is more and more frequent. This is the second digestive cancer after that of the colon. Over the past twenty years, we have seen a significant increase in its incidence. Currently, there are around 14,000 new cases per year. It is estimated to become the second leading cause of cancer death by 2030. The precise reasons for this worrying increase are not known. Several hypotheses are put forward. Pancreatic cancer could be favored by industrial foods and pesticides. Tobacco, obesity, old diabetes, chronic inflammation of the pancreas are known risk factors. Genetic parameters can also be involved. “5 to 10% of pancreatic cancers are related to family or genetic forms, underlines Dr Cindy Neuzillet, digestive oncologist at Institut Curie (Saint-Cloud). The most common genetic defect is aBRCA 1 or 2 gene alteration, involved in the repair of DNA breaks. It is found in certain familial forms of breast and ovarian cancer.
A new therapeutic approach to delay the progression of the disease
Pancreatic cancer is one of the cancers with a poor prognosis. Due to the late and generally non-specific clinical expression of the disease (fatigue, weight loss, etc.), the diagnosis is often made at an advanced stage. In 50% of cases it is diagnosed at a metastatic stage, in 30% of cases at a locally advanced stage and only 15-20% of patients are diagnosed at a stage where the tumor is resectable and can benefit from surgery. But even in the latter case, recurrences are frequent, which is why in operated patients, so-called adjuvant chemotherapy is necessary.
At the metastatic stage, the use of a new chemotherapy protocol, the Folfirinox, a combination of three molecules (oxaliplatin, folinic acid, irinotecan, 5-fluorouracil) instead of gemcitabine, which was the standard treatment, improved survival. “But not all patients can benefit from it because you have to be in good general condition,” says Dr Neuzillet.
The people with mutations in the BRCA1 and BRCA2 genes, could now benefit from a new specific therapeutic approach. This is theolaparib (Lynparza®), a treatment belonging to the family of PARP inhibitors. These drugs work by exploiting a weak ability of cancer cells carrying BRCA mutations to repair DNA damage.
THE’Phase III POLO study presented to ASCO showed that olaparib was effective in delay disease progression. After 2 years, 22.1% of patients receiving olaparib had no disease progression compared to 9.6% of those treated with placebo. It has been given to patients whose disease had previously been controlled with platinum-based chemotherapy (most often Folfirinox) for at least four months. “This is the first time that a new targeted therapeutic route has had effects on pancreatic cancer, immunotherapy, a source of hope in other tumors, has, for example, not given results.
“The results of this therapy are encouraging, believes Dr. Neuzillet, especially as some patients respond longer to treatment, with a response time of up to two years, which has never been seen before. “
As a result of this study, doctors will decide when it will be useful to screen for constitutional mutations in the BRCA gene. Knowing that the latter are infrequent, representing only 5 to 7% of patients.
Source: “Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial” (Abstract N ° LBA4).