Poor Disease Prognosis Due to Lack of Effective Treatment Options

Wednesday 23 April 2014, Amsterdam

The current Pancreatic Cancer (PC) therapeutics market is very limited, with only four drugs approved for the treatment of the disease. These are the generics gemcitabine and fluorouracil (5-FU) and the patented drugs Tarceva, by Genentech and Roche, and Abraxane, by Celgene. Abraxane was approved by the US Food and Drug Administration (FDA) in September 2013 and by the European Medicines Agency (EMA) in January 2014 (FDA, 2013).  

Since 1997, the standard of care in the treatment of advanced PC (approximately 80% of patients are diagnosed with advanced disease) has been gemcitabine therapy, either as a monotherapy or in combination. In combination, gemcitabine is often prescribed with off-label drugs that cause minor improvements in progression-free survival, and trends towards (although not statistically significant) OS - for example, Xeloda and Eloxatin. Either in combination or as a monotherapy, average Overall Survival (OS) with gemcitabine-based therapy is six months, while the five-year survival rate is less than 5%. The recently approved Abraxane has been shown, when in combination with gemcitabine, to increase OS to 8.5 months (Von Hoff et al, 2011). The FOLFIRINOX regimen, which uses a combination of folinic acid, 5-FU, irinotecan and oxaliplatin, has been shown to increase OS in advanced PC patients to 11 months, but only in those with a good performance status.

Even with Abraxane’s and the FOLFIRINOX regimen’s recent improvements in survival demonstrated with Abraxane and FOLFIRINOX, prognosis and survival chances are still substantially worse in PC than for other leading causes of cancer-related deaths, such as breast and lung cancer. There are noticeable gaps in treatment development, namely a lack of diagnostic tools and a lack of patient subset analysis and targeted therapies. As such, the marketed products are expected to remain dominated by gemcitabine and the off-label use of other chemotoxic agents, throughout the 2014–2020 forecast period.  


Forecast Drug Approvals to Result in Limited Market Growth and Minimal Change in Disease Prognosis

The drugs expected to be approved in the forecast period are expected to have little impact on the PC market, with a continued need for more targeted therapies. Potential targeted therapies that have previously been analyzed in clinical trials include vascular endothelial growth factor receptors and epidermal growth factor receptors, but with limited success. Numerous novel targets are being analyzed in the current developmental pipeline, many of which have not been investigated in a clinical setting before. These include insulin-like growth factor receptors, members of the Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) signaling pathway (KRAS is mutated in 90% of PCs) and signals leading to the development of a dense surrounding stroma, which is characteristic of pancreatic tumors. Such a high variation in molecular targets, the majority of which are in the Preclinical of the Phase I stage of development, and an attrition rate of 77% support the suggestion that there will be an influx of targeted therapies beyond the forecast period.