Precision Medicine - Biomarkers & Diagnostics

The First Diagnostic to Predict the Patient response in Pancreatic Cancer treatment

GemciTest® is an innovative and non-invasive In Vitro Diagnostic that predicts patient response to first-line gemcitabine therapy in pancreatic cancer. The benefits of this RUO predictive molecular test are to help choose the most adapted treatment, improve the patient’s quality of life during treatment and control healthcare costs.

Medical problems: Pancreatic Cancer

Pancreatic cancer is a “silent” disease that does not cause any symptom in its early stages. The majority of patients have metastases and/or are inoperable at diagnosis and, for them, chemotherapy remains the only therapeutic option (~80% of patients).
This cancer has a poor prognosis: 95% to 98% of patients with pancreatic cancer will succumb to the disease in the short or medium term (5-year survival rate = 5%).

Pancreatic cancer is one of the deadliest cancers in the Western world and is expected to soon become the second or third leading cause of cancer death, surpassing breast and colorectal cancer. If we compare pancreatic cancer with breast cancer (same stages 3 and 4), the 5-year survival rate in breast cancer is close to 72%. This rate has been achieved in part through the use of biomarkers or molecular tests to stratify patients and prescribe more targeted treatment.

This medical approach of “stratification” of patients thanks to biomarkers or molecular tests makes it possible to improve the drug management of patients, to prescribe to people the most adapted treatment, therefore the most effective (evaluation of toxicity, resistance, etc.), and also to reduce healthcare costs.

Gemcitabine is a generic molecule used in the treatment of patients with locally advanced or metastatic pancreatic cancer.
Other treatments, combination therapies of gemcitabine plus erlotinib and gemcitabine plus nab-paclitaxel, received approvals based on a very modest increase in survival compared to gemcitabine alone; i.e., median Survival (OS) gains of 0.3 and 1.8 months respectively with absolute survival gains at 1 year corresponding to 6% and 13%.
Folfirinox (a combination of four chemotherapies) is the first major advance in the management of pancreatic cancer since overall survival and survival times without recurrence have almost doubled (Conroy T et al. N Engl J Med 2011). However, the population studied in recent clinical studies is limited to patients in “good general condition” (SP 0 or 1)1 with satisfactory liver function2, thus excluding a large number of patients with metastatic pancreatic cancer. In addition, toxicities secondary to folfirinox treatment are important3. Thus, the safety and toxicity profile of folfirinox treatment is considered less positive than gemcitabine.

1. In non-resectable pancreatic cancer, the choice of chemotherapy treatment is made thanks to the scales of autonomy (PS : performance status), which make it possible to evaluate the general state of the patient. The most commonly used are the Karnofsky scale and the Zubrod scale (or ECOG: Eastern Cooperative Oncology Group). The choice of treatment is completed by the data acquired during diagnosis (see §”Description of uses and modes of use”).
2. bilirubin levels less than 1.5 times normal
3. The grade 3-4 neutropenia rate is 45.7% vs 21% in the gemcitabine group (p<0.001) with 5.4% febrile neutropenia versus 1.2%. Moreover, the occurrence of grade 3-4 diarrhoea (12.7% vs 1.8%) and grade 3 peripheral neuropathies (9% vs 0%) is much more frequent (Conroy T et al.).

Medical interest of the Gemcitest®

Without stratifying patients using biomarkers or molecular tests, the median survival rate of patients diagnosed with pancreatic cancer and treated with gemcitabine is 6.5 months, with a 1-year survival rate of less than 20%.

From a population of patients diagnosed with pancreatic cancer (grade 3-4, non-operable, metastatic or not), GemciTest® (RUO Diagnostic) identifies the subgroup of patients responding to gemcitabine (according to criteria of progression-free survival PFS and OS overall survival).

The GemciTest® (predictive molecular test of therapeutic response) can identify the following sub-populations of patients:
– patients not responding to gemcitabine: they represent 63% of patients with a median survival rate of 5 months and a survival rate at 1 year of less than 12%,
– Gemcitabine responders: they represent 37% of patients with a median survival rate of 15 months and a survival rate at 1 year greater than 65%.

The benefits associated with the use of this RUO Diagnostic in pancreatic cancer are:
– Identify patients whose PFS and OS levels go well beyond current treatments (greater than 15 months with a survival rate at 1 year of more than 65%),
– Avoid prescribing gemcitabine-responsive patients another treatment more toxic, harmful or inefficient,
– Therefore, to improve the quality of life of patients (general well-being, including stress level, sexual function and self-perceived health status), their families and caregivers during treatment, gemcitabine being the least “aggressive” treatment.

The GemciTest® concerns 80% of patients diagnosed with pancreatic cancer and its results will be obtained within 2-3 working days. This In Vitro Diagnosis is an example of the benefits of molecular tests that predict patient response to treatment. It is also an example of the benefits of Precision Medicine in the treatment of pancreatic cancer.
The GemciTest® thus makes it possible to facilitate precision taking by guiding the choice of therapy towards the least aggressive treatment and to improve the patient’s quality of life during treatment.

Analytical performance of the Gemcitest®

The analytical performance of GemciTest® (effectiveness of In Vitro Diagnosis, repeatability, inter and intra-sample variability, etc.) and its clinical performance have been confirmed (following the recommendations of the health authorities).

Briefly, the following graphs (Kaplan-Meyer type) and table show the main characteristics of the GemciTest® and its performance.

Cost savings generated by the Gemcitest®

Today, health actors are facing to several major problems: the reduction of overall expenditure on health systems, the growing need to improve the effectiveness of therapies, while respecting or improving the quality of life of the patient during treatment (reduction in the time taken to treat and inequalities in this treatment between territories).

Molecular tests predictive of patient response to one of the therapies are one of the most effective solutions to meet these needs by helping physicians choose the most effective and appropriate treatment for the patient.

The quality of life of the patient and the cost of the overall treatment (not just the molecule) in pancreatic cancer were evaluated in the US by a scientific team (Goldstein DA et al, Med Oncol 2016). This study described the monthly costs and overall treatment costs for gemcitabine, folfirinox and the combination gemcitabine plus nab-paclitaxel (named Abraxane® below). In addition to drug costs, the study includes administration costs and toxicity costs (including growth factor support, blood transfusion and hospitalizations for toxicities). Adverse event administration and management costs are based on Medicare reimbursement rates (a federally administered health insurance system for people over 60) for hospital and physician services. The study indicates that the choice of chemotherapy for pancreatic cancer should be based on the tolerance and efficacy of individualized treatment, depending on the patient’s condition.

The monthly costs for Gemcitabine, Folfirinox and Abraxane® are €1,200, €6,300 and €10,645 respectively. Therefore, the overall cost of treatment for the same treatment based on a median PFS is 4 392 € / patient for gemcitabine, 40.324 € / patient for folfirinox and 58.554 € / patient for Abraxane®.
Compared to first-line treatment with Abraxane® or Folfirinox without patient stratification, the use of GemciTest® in the decision-making process results in a 35% reduction in overall healthcare costs, while optimizing the overall well-being of the patient.
Using GemciTest in combination with Gemcitabine would save €24,613 per patient for a first-line treatment with Abraxane® and €15,827 per patient for a first-line treatment with Folfirinox.
Folfirinox and Abraxane are also associated with significant toxicities and side effects for patients, reducing their quality of life.

GemciTest® justifies its unique and innovative potential to:
i) facilitate decision-making by guiding the clinician towards the choice of optimal therapy,
ii) improve the patient’s quality of life during treatment,
iii) reduce and control overall health costs in pancreatic cancer.