There is perhaps no scarier word in the English language than "cancer." More than 15.5 million Americans who were alive as of Jan. 1, 2016, have had cancer at some point in their lives, according to the American Cancer Society, and it's expected to lead to 600,920 deaths in 2017. Cancer is currently the second most common cause of death in the U.S., behind only heart disease, but if a rising trend in cancer diagnoses continues, it'll soon become the leading cause of death in the United States.

However, we've also witnessed some incredible pharmaceutical innovations over the past four decades that have led to notably positive impacts on five-year cancer survival rates. For example, prostate cancer in men and breast cancer for women had five-year survival rates of 68% and 75%, respectively, between 1975 and 1977. By 2006-2012, these five-year survival rates were up to 99% and 91%, respectively. Strong improvements have also been seen in kidney and renal cancers, Hodgkin's lymphoma, and colorectal cancers, to name a few.

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Then again, there's still much work to be done. In more than 30 years, five-year pancreatic cancer survival rates are up to just 9% from 3%, liver cancer has jumped to only 18% from 3%, and lung cancer has improved by seven percentage points to 19%. While the numbers are trending in the right direction, they're simply nowhere near good enough.

Introducing the new foundation of cancer-fighting medicines

That's where cancer immunotherapies come in. Cancer immunotherapies represent a potentially new foundation of medicine to fight advanced types of cancer, often in cases where a patients' tumors express the PD-L1 protein. Cancer immunotherapies have a dual task. Firstly, they're designed to disrupt cancer's ability to go undetected by the immune system. Secondly, once cancer cells are identified as a foreign substance, immunotherapies help supercharge your immune system to kill cancer cells. Though cancer immunotherapies can be administered as a monotherapy, they've been shown to be exceptionally effective when administered in combination with existing chemotherapies.

Today, about a half-dozen cancer immunotherapies have received the green light from the Food and Drug Administration (FDA), with most approvals coming within the past year or so. However, it's the earliest immunotherapy approvals that are on track to deliver more than $1 billion in sales this year. Here are the three most successful immunotherapies as of now, based on sales.

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Opdivo

Bristol-Myers Squibb's (NYSE:BMY) Opdivo is currently on track to generate the highest sales among immunotherapies in 2017. Through the first half of 2017, Bristol-Myers reported $2.32 billion in worldwide sales, representing 50% growth from the first six months of 2016. 

Opdivo has been approved in a number of advanced cancer indications, including metastatic melanoma, second-line renal cell carcinoma, second-line non-small-cell lung cancer (NSCLC), head and neck cancer, and advanced urothelial carcinoma, to name a few of its indications. Just this past week, the company announced exciting new first-line data involving the combination of Opdivo and Yervoy in first-line renal cell carcinoma that led to a 37% reduction in risk of death compared with the current first-line standard of care, Sutent. 

However, it's important to note that not every clinical trial has led to success. In fact, Opdivo was once pegged for perhaps $10 billion or more in peak annual sales, but not necessarily any longer. Last year, the CheckMate-026 study in advanced first-line NSCLC patients failed miserably, opening the door for competitors to steal the spotlight in first-line NSCLC, a very lucrative indication. Despite the setback, though, Opdivo remains a foundational therapy for advanced cancer patients.

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Keytruda

If Opdivo is the cream of the crop among immunotherapies, then Merck's (NYSE:MRK) Keytruda is an exceptionally close second. Through the first half of 2017, Keytruda's worldwide sales have grown to $1.47 billion, which is more than what it generated in full-year sales in all of 2016. 

Keytruda is currently approved to treat advanced melanoma, second-line advanced NSCLC, advanced head and neck squamous cell carcinoma, advanced urothelial carcinoma, and first-line advanced NSCLC. You see, Opdivo's pain was Keytruda's gain in first-line advanced NSCLC when it easily hit its primary endpoint in patients whose tumors had at least 50% PD-L1 expression.

Merck's Keytruda also became the first drug ever (we're talking more than 110 years of FDA history) to be approved by the FDA to treat solid tumors with a specific genetic mutation. Label expansions are often given only when compared with a placebo or current standard of care, and essentially always for a specific cancer site. But Keytruda wound up producing an overall response rate of 77% in patients with advanced forms of pancreatic, prostate, uterus, or bone cancers with a specific mutation. By comparison, response rates in the 10% to 25% range are far more common for advanced cancer patients with these diseases.

Like Opdivo, Keytruda is being studied in seemingly dozens of early-, mid-, and late-stage trials, so its total sales figures are likely to head significantly higher over time.

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Yervoy

If we were to overlook the approval of cancer vaccine Provenge in 2010, the very first non-vaccine checkpoint inhibitor to make it to market was Bristol-Myers Squibb's Yervoy. Through the first half of 2017, Yervoy has generated $652 million in sales, representing a 29% improvement from what it produced through the first half of 2016.

Since being approved for late-stage melanoma in 2011, Yervoy has also received the FDA green light as a treatment to reduce the risk of a melanoma reoccurrence post-surgery, as well as in pediatric patients 12 and older with unresectable or metastatic melanoma.  Yervoy's best shot at future growth lies with its combination studies involving Opdivo. As noted, the Opdivo-Yervoy combination study in first-line renal cell carcinoma studies dazzled recently, leading to what very well could be a label expansion opportunity in 2018.

Of course, Yervoy has been far from perfect, and as a monotherapy it's taken a clear backseat to Opdivo. For instance, in 2013, Bristol-Myers announced that a study involving Yervoy in patients with metastatic castration-resistant prostate cancer failed to reach its primary endpoint of a statistically significant improvement in overall survival. At this point, Yervoy's hopes are pretty much tied to the hip of Opdivo via combination studies.

Sean Williams has no position in any of the stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy.