Fighting Cancer: Colorectal Cancer's Most Promising Treatments

As I noted four weeks ago, cancer statistics are both staggering and disappointing. Although cancer deaths per 100,000 people have been on the downswing since 1991 thanks to access to more effective medications and better awareness about the negative health effects of smoking, there is still a lot of research and progress yet to achieve. My focus in this 12-week series is to bring to light both the need for continued research in these fields, as well as highlight ways you can profit from the biggest current and upcoming players in each area.

Over the past three weeks we’ve looked at the three cancer types most expected to be diagnosed this year:

Today, we’ll turn our attention to the projected fourth-most diagnosed cancer type: the combination of colon and rectal cancer.

The skinny on colorectal cancer
Colorectal cancer is expected to be the fourth most commonly diagnosed cancer, but it's the second leading cause of death behind lung and bronchus cancer. Of the forecasted 580,350 deaths this year associated with cancer, 8.8% are likely to be caused by colorectal cancer -- a higher death incidence than both prostate cancer and breast cancer, according to the American Cancer Society (link opens PDF).

As we've seen with previous cancer types, better treatment and early screening options, and a higher level of awareness to cancer-causing agents, has definitely helped five-year survival rates for both colon and rectal cancer. The five-year survival rate for colon cancer was just 51% in 1975-1977 and just 48% for rectal cancer in the same period. By 2002-2008, those survival rates had improved to 65% for colon cancer and 68% for rectal cancer. Still, there's a lot of room for improvement with late-stage colon and rectal cancer producing a meager 12% five-year survival rate, and only 39% of all colorectal cancer being diagnosed in the localized stage.

It's also worth noting that those over age 50 -- whom the Centers for Disease Control and Prevention has focused its efforts to encourage early screening – have seen an annual decline of 4.1% in cancer incidence between 2005 and 2009 while those under the age of 50, who the CDC hasn't targeted, have seen a 1.1% increase in colorectal cancer incidence rates over the same period. This is an indication that screening rates for colon cancer, while improving, are still nowhere near where they should be for any age class.


Source: Centers for Disease Control and Prevention. Percentage of adults aged 50-75 who reported being up-to-date with colorectal test screening by state in 2010.

Treatment options for colorectal cancer often include a combination of surgery -- which can be curative if caught early enough -- and chemotherapy agents, as well as radiation and targeted therapies, if necessary. Unfortunately, with few early-stage symptoms, many people remain at risk -- especially those who are obese; are physically inactive; those who have diets comprised of lots of red meat; those who are regular smokers; and potentially those with type 2 diabetes. 

Where investment dollars are headed
Given that there exists a lot of room for improvement in both the late stage of colorectal cancer treatment and early-stage detection, investment dollars are clearly streaming into colorectal cancer research. Here's a look at some of the biggest current players in the field targeting advanced colorectal cancer.

  • Avastin: As I described last week, Avastin is Roche's (NASDAQOTH: RHHBY  ) wonder drug and is approved to treat a myriad of advanced stage cancers such as renal cancer, non-small-cell lung cancer, glioblastomas, and, of course, metastatic colorectal cancer. Avastin is one of the most successful colon cancer treatments in that it's approved by the Food and Drug Administration for both first-line and second-line treatments. Avastin gained first-line treatment approval in Febuary 2004 with trials showing an overall survival improvement in patients of about five months. In June 2006, it gained second-line treatment approval in combination with Folfox4 (the combination of 5-fluorouracil, leucovorin, and oxaliplatin), which resulted in a median overall survival improvement of 2.2 months. In January of this year, Avastin received another approval for Avastin in combination with flouropyrimidine-based chemotherapy after trials showed a median overall survival of 11.2 months as compared to 9.8 months in the control arm and a 1.7 month improvement in progression-free survival, or PFS. 
  • Zaltrap: Developed in collaboration between Regeneron Pharmaceuticals (NASDAQ: REGN  ) and Sanofi, Zaltrap works by the same mechanism as Avastin by blocking blood vessel growth leading to the tumor site in an attempt to starve it. Zaltrap was approved in August in combination with Folfiri (a combination of fluorouracil, leucovorin, and irinotecan) for the treatment of metastatic colorectal cancer. It has also since been approved in Europe. Median overall survival for the Zaltrap patient group was 13.5 months, and PFS was 6.9 months compared to 12.06 months in median OS and 4.7 months in PFS for the patient subset not taking Zaltrap.
  • Erbitux: Owned by Eli Lilly via its Imclone purchase, Erbitux was approved in July in combination with Folfiri as a first-line treatment for K-ras mutation-negative, EGFR-expressing metastatic colorectal cancer. Unlike Avastin or Zaltrap, Erbitux works by reducing hormones that promote colorectal cancer growth. In trials, median overall survival improved by just 1.1 months to 19.6 months as compared to 18.5 months in the control arm, while PFS improved to 8.9 months from 8.1 months. In addition to Erbitux's approval, Qiagen's Therascreen K-ras RCQ PCR kit was approved by the FDA to help identify these K-ras mutation-negative patients. Erbitux is approved to treat metastatic head and neck cancer as well. 
  • Vectibix: Developed by Amgen, Vectibix is approved to treat patients who've exhibited disease progression while taking or following fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy regimens in patients with EGFR-expressing metastatic colorectal cancer. In trials, Vectibix was compared against a control arm of just "best supportive care," or BSC, so it's a very late-stage treatment option. PFS for Vectibix was 96 days in trials versus the 60 days noted in the BSC control arm.
  • da Vinci surgical system: Intuitive Surgical's (NASDAQ: ISRG  ) robotic surgical system known as da Vinci is changing the face of colon and rectal surgery by introducing precise movements navigated by physicians. The end result of robotic surgeries has been smaller incisions, faster recovery times, and a similar adverse event profile to traditional laparoscopic surgeries.

Just as we've seen in all preceding common cancer types, FDA approvals are far from a guarantee. ArQule, for instance, saw its colorectal cancer drug tivantinib fail to stop cancer growth or improve median overall survival in late-stage trials in January. A personal holding in my own portfolio, Aeterna Zentaris and Keryx Biopharmaceuticals shared a similar fate a year ago when their late-stage trial for advanced colon cancer was stopped after it appeared perifosine wouldn't meet its primary endpoint of improving overall survival.

What's coming down the pipeline
Now that you have a better idea of what the current treatment scene looks like for colorectal cancer, let’s have a look at two of the revolutionary treatments coming down the pipeline that have a shot at drastically improving patient quality of life and survival rates.

  • Stivarga: This is a little bit of a stretch because Onyx Pharmaceuticals (UNKNOWN: ONXX.DL  ) and Bayer's Stivarga was approved last September, but we haven’t seen anywhere near what benefit this oral metastatic colorectal cancer drug could provide yet. Stivarga works by inhibiting numerous membrane-bound and intracellular kinases that are involved in normal cellular functions. All told, median overall survival was 6.4 months for Stivarga compared to just five months for the control arm, and PFS improved to two months versus 1.7 months for the placebo. As an added bonus, Stivarga is also approved by the FDA to treat advanced gastrointestinal stromal tumors.
  • Cologuard: As I mentioned previously, early colorectal screening is just as important, if not more important, to diagnose, stage, and treat this type of cancer. That's why Exact Sciences' (NASDAQ: EXAS  ) at-home diagnostic test could become a simple and effective way for everyday Americans to self-diagnose. For this diagnostic test, patients would collect a stool sample and send it into Exact Sciences for analysis. Under normal circumstances, millions of colon-wall cells are shed daily, each with their own unique, but normal, DNA. Similarly, polyps and tumors shed cells that express mutated DNA strains which are recognized by the diagnostic test, cuing doctors and patients into a more invasive examination.  

Your best investment
As you can see, there's still plenty of improvement yet to be seen in colorectal cancer care. However, there are also a lot of very good choices from an investing perspective.

For those of you with a penchant for a bit more risk, I'd suggest either looking into Onyx Pharmaceuticals whose Stivarga has the potential to become a $1.3 billion drug if it gains multiple indications according to analysts, or Exact Sciences whose revolutionary stool sample test could become a non-invasive staple of the early-detection screening process.

For those with an affinity for much less risk who still want to take advantage of the huge colorectal cancer market, your best bet is once again Roche with its blockbuster, Avastin. Avastin sales grew by 6% to $6.12 billion in 2012, and numerous treatment indications will keep sales of this drug high for many years to come. It also doesn't hurt that Roche is paying out an annual 2.9% yield.

Stay tuned next week when we tackle the current and upcoming therapies for the treatment of melanoma in this series on cancer.

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Help us keep this a respectfully Foolish area! This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above. Help us keep it clean and safe. If you believe a comment is abusive or otherwise violates our Fool's Rules, please report it via the Report this Comment Report this Comment icon found on every comment.

  • Report this Comment On March 28, 2013, at 7:21 AM, retiredpharma wrote:

    Sean,

    Nice job!

    Finally a FOOL who does some DD and not just another Blogger...I am long EXAS the second time around...I netted about $12K the last go around and now I am REBUILDING a new position as it has dipped recently sub $10 area.

    EXAS and Cologuard will become the new Dx std to replace FIT/FOBT and accompany Colonsocopy which are INCAPABLE of finding PRECANCERS/Polyps and the DeeP-C trial(waiting on Topline now) will substantiate the IP and provide FDA approval soon thereafter!

    We will eradicate CRC much the same way we have eradicated Cervical Cancer through the Pap Smear...this test mimics the practicality of the Pap in Cervical Cancer as its CUMMULATIVELY done Q 3 years and your DETECTION odds increase non invasively!

    Perfect for the Medicare crowd like me!

    retiredpharma

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