New Tools to the 4 Pillars of Cancer Treatment: Biomarker Testing and Chronic Cancers

Early cancer treatment, such as it was, was strictly surgical removal. During the mid-20th century, two more modalities came on, radiation and chemotherapy. Until recently, they were considered to be the three pillars of cancer treatment. Recent years have added a fourth pillar to surgery, radiation and chemotherapy—immuno-oncology.

An article in The Conversation noted, “This century’s approaches to developing new forms of chemotherapy are radically different from a generation ago. Our new understanding has identified specific weaknesses that can be targeted by ‘designer’ therapies, and treatments can increasingly be personalized to the cancer of any one individual.”

Although likely not quite “pillars,” there are two other trends (at least) in cancer treatment. One is related to personalized medicine and is the notion that all cancers are increasingly being seen as rare cancers. The other is the treatment of some types of cancers as chronic diseases.

All Cancers Are Rare Cancers

In Europe, rare cancers are classified as having a prevalence of fewer than five cases out of a population of 10,000. The International Rare Cancers Initiative (IRCI) defines rare cancers as having an incidence of three or fewer newly diagnosed people out of a population of 100,000 per year. Others define it as six or less than 100,000. And the U.S. National Cancer Institute (NCI), for example, notes that “using either definition or cut-off, virtually all pediatric cancer types would be considered ‘rare cancers.’”

But the point actually is that due to improvements in genomic and genetic testing, physicians and drug companies are increasingly able to target the best drugs for smaller and smaller subpopulations of cancer patients. For example, in April 2018, the U.S. Food and Drug Administration (FDA) approved AstraZeneca’s Tagrisso (osimertinib) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) in tumors with epidermal growth factor receptor (EGFR) mutations.

That’s only one example of approvals that say something along the lines of “Drug A is approved for third-line treatment of Cancer B that has positive C results and negative D results in patients who have been unresponsive to platinum-based chemotherapy and other immunotherapies.”

Another example is in 2018, Bristol-Myers Squibb announced data from its CheckMate -227 Phase III clinical trial of Opdivo (nivolumab) and Yervoy (ipilimumab) in first-line advanced non-small cell lung cancer (NSCLC) patients with high tumor mutational burden, which means the patients had 10 or more specific mutations.

Increasingly, tumors are being extensively tested for specific biomarkers that help target the most effective drugs and treatment modalities. In a related story, on Feb. 28, Guardant Health announced positive results from its NILE study comparing its liquid biopsy test, Guardant360, which uses a blood test compared to standard-of-care biopsy in first-line advanced NSCLC. The test identified guideline recommended-biomarkers in 77 patients, while traditional tissue testing identified them in 60. The test also identified the biomarkers associated with biomarkers for FDA-approved drugs, such as EGFR, ALK, BRAF, and ROS1.

Cancer as a Chronic Disease

Although less common, there are cases of cancer where certain drugs—also specific to certain genes and biomarkers—do not “cure” cancer, per se, but diminish the tumors to the point where they are controlled. The Wall Street Journal recently discussed this in an article titled, “New Cancer Drugs Aim to Offer Alternatives to Chemo.”

One example is Michelle Lowry, who was diagnosed at the age of two with a tumor caused by what is known as an NTRK fusion, where the NTRK gene fuses with another gene. They are observed in about 1 percent of solid tumors and can occur in almost any body tissue.

Michelle was enrolled in a clinical trial involving larotrectinib, which is marketed by Bayer and Loxo Oncology under the trade name Vitrakvi. Within only days of receiving Vitrakvi, the tumors shrank. Now Michelle is, as the WSJ writes, “a happy 3-year-old who loves Disney princesses and belting out Vampirina songs, doing puzzles, and helping her parents cook.”

On the one hand, the drug is just another example of treating a cancer based on specific genetic biomarkers. Although it appears to have “cured,” Michelle, in some cases these drugs shrink the tumors to where they’re manageable, but do not kill them entirely.

Leo Mascarenhas, deputy director of the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles, who is also one of Michelle’s doctors, told the WSJ, “While we may not be able to cure cancer, we may be able to control it much like we do with high blood pressure or diabetes.”

Vitrakvi’s side effects are mild to moderate compared to chemotherapy. Vitrakvi is given orally twice a day. Side effects can include dizziness, anemia, fatigue and abnormal liver function test results. The list price of the drug ranges from $11,000 to $32,800 per month, based on dosage.

The WSJ writes, “Some experts caution that treatments like larotrectinib won’t become the mainstay of cancer treatments. Dr. (David) Hyman (head of larotrectinib’s clinical trials and chief of early drug development at Memorial Sloan Kettering Cancer Center) says the location of cancer will still play an important factor in drug therapy. ‘The type of cancer a patient has will continue to be really important in a lot of settings.’”

Another example is Keith Taggart, 61, in Oklahoma City. His salivary gland tumors spread to his lungs, liver and kidneys. He thought he had three to four weeks to live. He’d already had numerous surgeries, as well as radiation and chemotherapy. He enrolled in a clinical trial for larotrectinib.

“Many of the tumors I could feel with my hands were gone within about four days,” he told the WSJ. “My first scans four weeks later found that most of the tumors were gone and the ones that were there had reduced by 65 percent.”

Two years later he’s still alive and still taking the drug. “I still have some tumors but they are so small that it’s not even necessary to have surgery,” he told the WSJ. “It’s completely manageable.”

The American Cancer Institute notes that “cancer isn’t always a one-time event. Cancer can be closely watched and treated, but sometimes it never completely goes away. It can be a chronic (ongoing) illness, much like diabetes or heart disease.”

Although patients are much more likely to want the disease to be completely eradicated, having the cancer be managed and stay alive is a second-best alternative, and just another tool in oncologists’ toolbox.