There is no making light of the fact that cancer is a terrible disease, claiming more lives in the U.S. each year save for heart disease. What's even scarier is that cancer prevalence is rising in the U.S., whereas a number of other leading causes of death are shrinking because of improved awareness and better pharmacologic solutions.

If there are positives to come out of this, it's that improved awareness of cancer risk factors has helped some people alter their lifestyle habits in an effort to lower their risk of getting cancer in the first place. In addition, we've learned that some cancers are actually quite beatable with early detection. In other words, a cancer diagnosis isn't necessarily a death sentence as many people once feared it was.

Source: Bill Branson, Wikimedia Commons.

However, not all cancers are created equally -- and perhaps none is more rightfully feared than a pancreatic cancer diagnosis. When examining the 12 most-diagnosed cancers last year, pancreatic cancer ranked 12th in diagnosing prevalence, with 45,220 cases estimated to be reported in 2013, but it ranked extremely high in total male and female cancer deaths, according to the American Cancer Society. In fact, overall five-year pancreatic cancer survival rates have improved from just a paltry 2% in 1975-1977 to 6% in 2002-2008 -- and as I noted in May, this had more to do with risk factor awareness than major pharmacologic improvements.

Five states with the highest prevalence of pancreatic cancer
Today, I want to look at what five states are exhibiting the highest prevalence of pancreatic cancer cases, as well as examine some of the revolutionary treatments that are working their way through the pipeline to treat this difficult type of cancer.

Here are the five states that, according to the Centers for Disease Control and Prevention, are currently boasting the highest incident rate of pancreatic cancer: 

State

Age-Adjusted Incidence Rate

Hawaii

13.8

New York

13.6

Maine

13.5

Connecticut

13.2

Pennsylvania

13.2

Source: Centers for Disease Control and Prevention, rates per 100,000 people for men and women, based on 2010 data.

To add some context to these figures, the national average incidence rate of pancreatic cancer is just shy of 12 cases per 100,000 men and women, with the nation's lowest reading coming from Wyoming at 6.6 cases per 100,000 people.

What's particularly disappointing about pancreatic cancer is that surgical resection -- which is often difficult given that the cancer is often discovered in an advanced stage -- is rarely successful in curing pancreatic cancer. Relapses of the cancer and metastases are unfortunately quite common. As you can see below, median overall survival based on diagnoses is generally poor.


Source: American Cancer Society; data from Bilmoria.

Perhaps one of the most obvious reasons that Hawaii, New York, Connecticut, and Maine lead this list is that they're somewhat common retirement locations. Getting older is one of, if not the, biggest risk associated with pancreatic cancer risk. A number of hypotheses exist as to why this occurs, but generally speaking it's believed that a number of toxins accumulate as we age and may be involved in spurring cancer development when we get older.

As should come as no surprise, smoking is another contributing factor to pancreatic cancer. In this case, though, smoking doesn't appear to be the primary factor leading to an increase in these Northeastern U.S. states (with the exception being Hawaii). Not one of these states ranks among the top 10 in terms of percentage of smokers. 

Perhaps a better explanation, and one we explored last week, would be trace elements of carcinogens being found in the soil and water supply in the Northeast or Appalachian region, including arsenic, cadmium, and nickel. The reason I bring this up is that there's once again (with the exception of HawaiI) a west of the Mississippi River bias in the concentration of pancreatic cancer cases. Excluding Hawaii, and adding Louisiana into the equation, 11 of the top 12 states in terms of pancreatic cancer rates are located in the Eastern half of the country.


Source: Centers for Disease Control and Prevention; incidence rates per 100,000 people.

How we're currently treating pancreatic cancer
I certainly don't want to make it seem like biopharmaceutical companies have sat on their hands when it comes to treating pancreatic cancer over the past four decades, but treatment improvements have been few and far between.

The two primary therapies given to treat advanced pancreatic cancer are Pfizer's (PFE 0.34%) Sutent and Novartis' Afinitor. Sutent practically doubled the progression-free survival of the placebo it was tested against at 10.2 months versus 5.4 months, however no complete responses were observed in its clinical studies. For Afinitor, progression-free survival checked in at a very comparable 11 months compared to just 4.6 months for the placebo.

Another therapy occasionally given to patients is combination drug folfirinox which has been shown to be effective on a number of difficult-to-treat cancers, but is also very toxic, meaning few patients last very long on the therapy.

Finally, Celgene's (CELG) Abraxane was recently approved to treat advanced pancreatic cancer in combination with Eli Lilly's Gemzar. Although the risk of death was reduced by 28% by the addition of Abraxane, and PFS improved 1.8 months, only 9% of patients were still alive just two years following initial dosing.

This isn't to say that other biopharmaceutical companies haven't tried to develop new pancreatic cancer therapies. Clovis Oncology retired its mid-stage therapy CO-101 in late 2012 after the drug failed to provide a statistical benefit over Gemzar which is another prescribed therapy. Also, just this past December, Onconova Therapeutics saw its share price tank after its leading drug prospect, rigosertib, when given in conjunction with Gemzar, failed to improve median overall survival. It's not as if these companies aren't trying, but pancreatic cancer is a difficult disease to treat.

New ways of treating pancreatic cancer
While far from a sure thing, there are three unique ways that researchers are now attempting to fight pancreatic cancer that are working their way through clinical trials.

The first, as we've looked at recently, are cancer immunotherapies which work by retraining the body's immune system to recognize and attack currently suppressed cancer cells. One company leading this charge is NewLink Genetics (NLNK).

NewLink's experimental therapy, algenpantucel-L, works by encouraging modified cancer cell lines to express alpha-gal, which is a carbohydrate that the human body has a natural immunity to. The body's immune system begins to recognize this carbohydrate and to attacks cells (in this case cancer cells) that express alpha-gal. Currently, NewLink is enrolling patients for its phase 3 studies in pancreatic cancer which, in phase 2 studies, showed an impressive 62% disease-free survival rate in its resected pancreatic cancer study after one year -- a notable improvement considering the high relapse rate.

Another unique way of attacking pancreatic cancer is by focusing on cancer stem cells rather than on cancerous cell growth. These stem cells are often immune to chemotherapy treatment and they could be the origin for relapses and metastases, so their eradication could make a big difference in resectable cases of pancreatic cancer.

The company working this angle is OncoMed Pharmaceuticals (OMED), which in December signed a mammoth collaborative deal with Celgene. Currently in the early phases of treatment, OMP-59R5 is being tested as an anti-cancer agent in advanced pancreatic cancer as well as non-small cell lung cancer. In addition to blocking cancer cell differentiation, OMP-59R5 is believed to also suppress blood vessel growth, which is crucial to solid tumor development.

Last, but certainly not least, we have Threshold Pharmaceuticals (NASDAQ: THLD) which is attempting to treat pancreatic cancer, and a number of other cancer types, via tumor hypoxia. The idea behind Threshold's therapies is that solid tumor growth tends to be willy-nilly, for lack of a better phase, and that out-of-control growth rate can lead to areas of the tumor that outpace blood vessel growth. These low-oxygen, or hypoxic, regions of the tumor are perfect targets for Threshold's lead drug, TH-302, since hypoxic cells are a rarity among healthy cells.

Currently, Threshold has an ongoing phase 3 trial known as MAESTRO, which is planning to enroll up to 660 pancreatic cancer patients. In phase 2 studies TH-302 delivered a 41% reduction of risk for disease progression and represented a 2.4 month median PFS improvement over the control arm.

Clearly there's still a long way to go with regard to improving treatment options, but we appear to be headed in the right direction.