The Past, Present, and Future of Lung Cancer Treatments

The Past, Present, and Future of Lung Cancer Treatments

Lung cancer, which accounts for 14% of all new cancers, remains one of the deadliest cancers in the United States, causing nearly 160,000 deaths in 2013.

Over the past few decades, lung cancer treatments have improved, and smoking rates have dropped from 42% in 1965 to 18% in 2012, but lung cancer and other respiratory diseases remain the third highest cause of death in the United States.

Therefore, let's take a closer look at how treatments from companies like Roche , Pfizer , Clovis Oncology , and Inovio Pharmaceuticals could shape the future of lung cancer treatments.

Understanding lung cancer
When we discuss lung cancer, two types are usually mentioned -- non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

NSCLC is far more common, accounting for 85% to 90% of all lung cancer cases, and is split into three main subtypes: adenocarcinomas (40% of NSCLC cases), squamous cell carcinomas (25% to 30%), and large cell carcinomas (10% to 15%).

Squamous cell carcinomas occurs more frequently in smokers, while adenocarcinomas occur more often in non-smokers, although they are not exclusive to either group. Large cell carcinomas can occur in either group, and it can be more aggressive and harder to treat than the other two types.

SCLC, which is far less common than NSCLC, mainly occurs in smokers and is characterized by smaller cancer cells that start spreading from the bronchi in the middle of the chest.

Standard treatments are Roche's territory
Since NSCLC is far more common than SCLC, there are more targeted treatment options for the former than the latter.

The most common first-line treatment for NSCLC is Roche's Avastin, which inhibits the growth of new blood vessels that can help cancer cells spread. Avastin is also approved as a treatment for colorectal cancer, renal, ovarian, and brain cancers.

Since Avastin is approved for such a wide variety of indications, it is also one of Roche's top-selling drugs, generating $3.45 billion in worldwide sales in the first half of fiscal 2013.

The market for second-line treatments for NSCLC is dominated by Roche's Tarceva, another top drug that generated $769 million in sales during the first half of 2013. However, Tarceva is only effective in NSCLC patients whose cancer cells have an overexpression or mutation of tyrosine kinase, an epidermal growth factor receptor (EGFR).

Both Avastin and Tarceva are administered alongside standard chemotherapy treatments such as Eli Lilly's Alimta and generic versions of Sanofi's Taxotere (docetaxel).

The growing market for targeted mutation treatments
Since Roche's footprint in NSCLC treatments is so large, other companies, such as Pfizer and Clovis Oncology, have tried to carve out new niche markets with treatments targeting specific mutations of NSCLC instead.

Pfizer's Xalkori targets a specific mutation of NSCLC cells known as ALK. ALK mutations only occur in NSCLC patients with adenocarcinomas, and account for approximately 5% of all lung cancer cases. Xalkori, which was approved by the FDA in 2011, was shown during clinical trials to shrink tumors by 50% to 60% in ALK-positive patients. It also exhibited a progression-free survival rate of 7.7 months versus three months on chemotherapy alone.

Clovis, on the other hand, is targeting another specific mutation known as T790M, which only occurs in 1% to 4% of all lung cancer cases. T790M is a resistance mutation to EGFR that renders Tarceva ineffective. Clovis' CO1686, which is currently in a phase 1/2 trial, could be the first targeted treatment for T790M mutations if approved. An earlier phase 1 trial showed that CO1686 was effective at shrinking tumors in 3 out of 4 patients.

Although the size of Pfizer and Clovis' prospective markets are smaller than Roche's, analysts predict that Xalkori and CO1686 (if approved) could respectively hit peak sales of $1.3 billion and $1.2 billion.

Will a lung cancer vaccine ever be approved?
Looking farther into the future, we should consider next-generation treatments such as therapeutic cancer vaccines. Therapeutic cancer vaccines, also known as immunotherapy treatments, are drugs that attempt to teach a patient's immune system to recognize cancer cells so they can be naturally destroyed.

One of the brightest hopes for a real NSCLC vaccine was Merck KGaA (not to be confused with the U.S. Merck ) and Oncothyreon's Stimuvax, now known as tecemotide. Unfortunately, the drug failed phase 3 trials in December 2012.

Merck, however, continued pushing ahead with an Asian study in an attempt to salvage the drug. Last September, the company announced that it was doubling down on tecemotide in new trials.

Meanwhile, Inovio Pharmaceuticals' pipeline of synthetic DNA-based vaccines are also worth watching. Inovio uses electroporation, a proprietary delivery system that uses brief electric pulses to boost cellular intake of its vaccines. The addition of synthetic DNA makes the vaccine slightly different from native human proteins and triggers the desired immune system response.

Inovio is primarily focused on cervical dysplasia and cancer vaccines, but it also has vaccines for hepatitis B/C, prostate cancer, influenza, malaria, HIV, breast cancer, and lung cancer in its vast pipeline. Inovio's breast and lung cancer vaccine, INO-1400, is currently in preclinical trials, but it could gain a lot of attention if its other vaccines prove that the company's method of electroporation delivery of synthetic DNA is viable.

The Foolish takeaway
In conclusion, lung cancer treatments have come a long way, but there's still plenty of room for new treatments -- the overall five-year survival rate for all stages of lung cancer is still only 16%.

While it's unlikely that next-generation vaccines will displace chemotherapy, radiation therapy, surgery, and targeted treatments anytime soon, they could one day render those old treatments obsolete.

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