Issue No. 59: Cancer Death Rate Registers a Record Decline; Reminder That Drugs Have Massive Benefits as Well as Costs

With all the debate over drug costs, it’s important to remember that pharmaceuticals also have massive benefits. Lives are extended or saved, pain and disability are reduced, suffering patients become more happy and productive, and burdens are lifted from their families.

Consider cancer, which, after heart disease, is the number-two cause of mortality in the United States. Two in every five Americans will get cancer in their lifetimes, with 1.8 million new cases expected in 2020. One in nine men will get prostate cancer; one in eight women will get breast cancer; one in 16 Americans will get lung cancer. Overall, cancer kills about 600,000 Americans a year; it’s the cause of 21% of all deaths.

But over the past quarter-century, the cancer death rate (that is, mortality per 100,000 Americans) has fallen an incredible 29%. Among black males, the demographic group with the highest death rate, the decline has been close to 50%. The American Cancer Society (ACS) estimates that 2.9 million fewer deaths have occurred than if the peak rates of the late 1980s and early 1990s had persisted.

Most dramatically, the death rate from cancer registered the largest one-year drop ever recorded, 2.2%, between 2016 and 2017, according to an ACS report released on Jan. 8.

There are several reasons for the decline: the reduction in tobacco use, earlier detection through better imaging techniques, improved surgical procedures, and new medicines and vaccines. A study by Seth Seabury and colleagues, published in the Forum for Health Economics and Policy in 2016, estimated that 73% of the success in fighting cancer is attributable to drugs.

The Promise of Immunotherapy

One of the most dramatic advances recently has been the use of drug-based immunotherapy, which enlists patients’ own immune system to kill tumors. As of December, the Food & Drug Administration had approved immunotherapy to treat about 20 different kinds of cancer, including bladder, kidney, lung cancer, leukemia, and non-Hodgkin’s lymphoma.

Immunotherapy is not a panacea. Currently, only a minority of patients respond positively to individual immunotherapy drugs, and immunotherapy has not proven significantly effective for three of the most common types of cancer: breast, prostate, and colon. More research and innovation are needed.

Still, recent declines in mortality because of immunotherapy are particularly striking for metastatic melanoma, or skin cancer that had spread to other organs, according to a new ACS paper. Death rates fell from an average reduction of 1% a year between 2006 and 2010 for men and women aged 50 to 64 years to 7% between 2013 and 2017. In other words, mortality rates in metastatic melanoma fell by a total of one-fourth in just four years.

A breakthrough occurred when James Allison, who, since the late 1970s, had been exploring the theory that the immune system can be manipulated to recognize cancer and mobilize cells to fight it, developed the drug ipilimumab, patented in 2011 by Bristol-Myers Squibb under the brand name Yervoy. (In 2018, Allison, affiliated with the MD Anderson Cancer Center, won the Nobel Prize.)

Former President Jimmy Carter, at age 90, was diagnosed in August 2015 with Stage IV melanoma that had spread to his brain. He said he had only a “few weeks left,” but he was successfully treated with radiation and a new immunotherapy drug developed by Merck called pembrolizumab, or Keytruda, which had been approved by the FDA less than a year earlier. Carter, four and a half years later, is still alive, and Keytruda has been approved for many other cancers as well, including lung, renal cell, esophageal, and cervical.

William G. Cance, chief medical officer for ACS, cited the “accelerated drops” in melanoma mortality thanks to immunotherapy as “a profound reminder of how rapidly this area of research is expanding, and now leading to real hope for cancer patients.”

The Case of TKIs for CML

Immunotherapy is not alone as an effective drug treatment for cancer. In May 2001, the FDA approved imatinib, a tyrosine kinase inhibitor (TKI), marketed by Novartis as Gleevec. The drug fights chronic myelogenous leukemia (CML), a cancer in which too many white blood cells are being produced in bone marrow. Tyrosine kinases are enzymes that promote cell growth, and a TKI like imatinib can inhibit their activity. Several generic manufacturers started producing imatinib after Gleevec went off-patent in 2016, and Novartis has since developed another TKI called nilotinib.

In addition to generics, there are five different branded TKIs, including Pfizer’s Bosulif and Takeda’s Iclusig, to fight CML. While it is not yet proven that any of these drugs can cure the disease, CML is being tamed; some 80% of patients are surviving at least 10 years, compared with 20% before imatinib reached the market.

Medicines to battle CML are not inexpensive, but their benefits far outweigh their costs. According to a 2012 study by Wesley Yin and colleagues in the American Journal of Managed Care, “Cost analyses indicate that the TKI drug class in CML therapy has created more than $143 billion in social value. Approximately 90% of this value is retained by patients and society, while approximately 10% is recouped by drug companies.”

The Yin study appeared four years before the imatinib generics and the same year that the FDA approved Bosulif and Iclusig. Today, the value retained by patients and society is undoubtedly far higher.

Economic Value of Progress in Fighting Cancer

In an earlier study, Frank Lichtenberg of Columbia University took a broader view. Lichtenberg wrote:

Based on the average cancer drug expenditure per cancer patient from diagnosis until death over the past decade, my analysis shows that the cost of [an] added year of life—plus any further benefits to people’s quality of living—was about $6,500. Given that surveys have estimated that most Americans would be willing to pay between $100,000 to $300,000 to extend their lives by one year —$6,500 represents a true bargain….

It’s worth remembering that…expensive drugs remain outliers in the grand scheme of cancer therapies. What’s more, drug prices usually decline steeply after patents expire and the drugs become available as generics, yet the ability of companies to charge high prices for a brief window provides incentive for the pharmaceutical industry to keep the wheels of innovation turning. This system may do a pretty good job of balancing society’s need for innovation as well as access.
 
In a separate 2004 National Bureau of Economic Research paper, Lichtenberg wrote that “since the lifetime risk of being diagnosed with cancer is about 40%, the estimates imply that new cancer drugs accounted for 10.7% of the overall increase in U.S. life expectancy at birth.”

In 2010, Darius Lakdawalla of the University of Southern California, along with five colleagues, including Tomas Philipson, who was then an economics professor at the University of Chicago and now heads the President’s Council of Economic Advisers, wrote a detailed study in the Journal of Health Economics of the economic effects of the war on cancer, declared in 1971 by President Nixon.

Lakdawalla and his colleagues determined that by 2000, the increased life expectancy was much greater, and like Lichtenberg and Yin, the vast majority of increased value flowed to patients and society:

Between 1988 and 2000, life expectancy for cancer patients increased by roughly four years, and the average willingness-to-pay for these survival gains was roughly $322,000. Improvements in cancer survival during this period created 23 million additional life-years and roughly $1.9 trillion of additional social value, implying that the average life-year was worth approximately $82,000 to its recipient.

Health care providers and pharmaceutical companies appropriated 5–19% of this total, with the rest accruing to patients. The share of value flowing to patients has been rising over time. In terms of economic rates of return, R&D investments against cancer have been a success, particularly from the patient’s point of view.

The researchers calculated that “drug companies, hospitals, doctors, and health professionals” earned at most $393 billion in profits over this time period,” compared with the net surplus to patients of nearly $2 trillion. This study is not new, but it is thorough and widely cited, and its conclusion holds up today.

In Three Years, 36 New Cancer Drugs

In the next edition of this newsletter, we will provide a complete rundown on new drugs approved in 2019, but for now, let’s continue to focus on cancer. It is worth quoting at length the section on cancer drugs in the annual report of the FDA’s Center for Drug Evaluation and Research (CDER), issued earlier this month:

2019 was another strong year for making new cancer and blood therapies available to patients in need. We approved new advances for certain patients with prostate cancer, bladder cancer, breast cancer, and lung cancer. We also approved two new bone marrow cancer therapies.

Additionally, CDER approved another new cancer therapy that can be used to treat any kind of tumor that has a specific genetic marker, as opposed to where in the body the tumor originated --- only the third cancer therapy approved by the FDA to target treatment based on a specific characteristic of a tumor instead of its site of origin.

Also to help advance cancer therapies, CDER approved a new drug to treat certain adult patients with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, a type of blood cancer. CDER also approved a new therapy for patients with mantle cell lymphoma, also a form of blood cancer that causes blood clots that can cut off oxygen and blood supply to the major organs and cause strokes and heart attacks that may lead to brain damage and death…. We also approved a new therapy for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, similar blood cancers that occur in different parts of the body.

In all, the FDA has approved 36 novel cancer drugs in the last three years. In addition, drugs that were first approved for one particular indication, like the immunotherapy Keytruda, have been approved for many more.

Developing these drugs is expensive and time-consuming. A study published in 2015 in the journal Cell concluded that ipilimumab, the treatment for metastatic melanoma “resulted from research conducted by 7,000 scientists at 5,700 institutions” over a period of a century. Remember that the average cost of bringing a single drug, of any sort, to market is about $3 billion, as this Scientific American article explains.

In addition to medicines that directly treat cancer, vaccines can prevent it from ever developing. For example, the human papillomavirus (HPV) has been linked, according to ACS, “to cervical, anal, throat, vulvar, and penile cancers. In fact, most cervical cancers are caused by infection with HPV.” A vaccine can stop the virus from developing. Similarly, a vaccine combats the hepatitis B virus, which puts people at higher risk of liver cancer. And eight new, competitive drug treatments developed in the past six years can completely eliminate the hepatitis C virus, which also can lead to liver cancer.

‘Where You Want to Get Cancer’

Since 1975, the proportion of people diagnosed with specific cancers who have survived at least five years has risen by 54% for lung cancer, 36% for colon, 50% for prostate, and 21% for breast.

For breast cancer, five-year survival rates vary widely, based on the stage at which detection occurs. The rate is 99% for localized disease, 85% for regional disease, and 27% for distant-stage disease, according to a 2017 ACS report. Overall for breast cancer, the rate is 90%; for prostate cancer, 98%; for melanoma, 92%.

The National Cancer Institute now lists 71 drugs to treat breast cancer, and new treatments are being developed all the time. For example, last month, the FDA granted “Breakthrough Therapy Designation” to the “addition of tucatinib to trastuzumab (Herceptin) and capecitabine for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer,” including cancer that has spread to the brain.

Progress against all cancers will depend on advances in detection and on new medicines, and the source of most of those medicines will undoubtedly be the United States. According to PhRMA, the trade association, some “1,100 medicines and vaccines for cancer…are in clinical trials or awaiting review by the U.S. Food and Drug Administration.”

As a Wall Street Journal editorial headline put it earlier this month, the U.S. is “where you want to get cancer.” The piece cited a study in The Lancet last year that found that someone diagnosed with pancreatic cancer between 2010 and 2014 had nearly twice the likelihood of surviving five years in the U.S. than in the U.K. The five-year survival rate for brain cancer was 36.5% in the U.S., 27.2% in France, and 26.3% in the U.K. For stomach cancer: 33.1% in the U.S., 26.7% in France, and 20.7% in the U.K.

An earlier study that looked at survival results for five common cancers in seven rich countries, as related by the U.S. Centers for Disease Control, found the U.S. performing best by far. That study looked at proportion of patients with different kinds of cancers surviving at least five years. The United States was number-one out of the seven countries for three of the five cancers (breast, colon, and prostate), second in lung cancer, and sixth in childhood leukemia. No other country came close to that record. 

A PhRMA analysis last year, using data from the research firm IQVIA, as well as the FDA, the European Medicines Agency, and Japan’s Pharmaceuticals and Medical Devices Agency, compared how broadly and quickly new cancer medicines became available in 15 rich countries, many of which set prices artificially low.

The U.S. was, far and away, and the leader. Some 96% of the new drugs were available in the U.S.; Germany and the U.K. tied for second with 71%, with Canada at 57% and Japan at 50%; the median was just 62%. The average delay in the public’s access to the new cancer medicines was a mere three months in the U.S., again by far the best. French patients could not gain access to the average new drug for 19 months; Italy, 20 months; the U.K., 11 months. The median among the nations was 16 months.

A survey in 2018  identified 65 new cancer drugs launched between 2011 and 2017 and found that “nearly all were available in the United States (62 medicines or 95 percent) compared to 75 percent in the United Kingdom and 51 percent in Japan.”

The country that develops drugs first gives the fastest and the most comprehensive access to those drugs. And it is an advantage that is becoming glaringly obvious as the development of cancer drugs accelerates. That system, as it pertains to pharmaceuticals, is currently under severe attack, and opponents might want to remind themselves that research has shown clearly that the benefits of cancer drugs far outweigh their costs.