Is a Revolution in Cancer Treatment Within Reach?

 

“Carol MacKenzie had just finished playing a round of golf when she noticed some swelling and pain in her neck. It was 2014, and 18 years had passed since Ms. MacKenzie finished treatment for breast cancer. But it had returned. This time the cancer was growing inside several lymph nodes around her neck, plunging her back into treatment long after she thought that was all behind her.

Doctors do not know exactly why or how breast cancer can go dormant in a patient’s body for so long, not advancing for years, until it suddenly begins to grow. But that’s what had happened. Without treatment, Ms. MacKenzie’s cancer would most likely have made its way to her vital organs and killed her.

But in the nine years since Ms. MacKenzie’s cancer reappeared, her physician, Dr. Nancy Lin, a medical oncologist at Dana-Farber Cancer Institute in Boston who specializes in treating and studying advanced breast cancer, has prescribed her a series of eight drug regimens, including three as part of clinical trials. Ms. MacKenzie, 71, of Massachusetts, switches from one medication to another when it becomes clear that a treatment doesn’t work or has stopped working because her cancer has figured out how to resist its effects. Some of these regimens have lasted only a few months, while others have kept Ms. MacKenzie’s cancer under control for longer. Of an oral type of chemotherapy she tried as her fifth line of treatment, she said: “I was excited. I got 12 months out of that one.”

Like a hiker who comes upon a wide creek and gingerly steps from one partially submerged stone to the next, Ms. MacKenzie has moved from one regimen to another, each drug or drug combination keeping her cancer in check long enough to get to the next one — until finally, in 2020, she started taking a medicine that for more than two glorious years has stopped her cancer from growing and given her a quality of life that’s very close to normal.

“Of all the things I’ve been on, it’s the easiest,” Ms. MacKenzie said. These days, she is more focused on her grandchildren’s hockey and football games than the fact that she has a supposedly fatal disease. In January, she and her husband celebrated their 50th wedding anniversary.

If you know someone with late-stage cancer, this kind of treatment regimen might be familiar to you. The approach is increasingly becoming a standard of care for patients facing diagnoses that were once death sentences.

Thanks to a combination of forces, cancer drug development is now happening fast enough that for patients like Ms. MacKenzie, it is outpacing the growth of cancer cells inside their bodies. For these patients, cancer is more like a chronic disease than a one-time catastrophic event.

Every time a new cancer treatment approach emerges, oncologists and over-excited journalists have a habit of declaring that a cure for cancer is imminent. What’s happening now is different. Rather than a single breakthrough therapy or discovery, a variety of scientific advances are exerting downward pressure on cancer mortality in new ways and at the same time. As a result, the landscape for many cancer patients has changed tremendously in just the past five years. The Cancer Moonshot, a multi-billion-dollar initiative championed by President Biden, aims to cut the cancer death rate by 50 percent in the next quarter century. The goal is lofty, but recent progress against cancer means it’s now less far-fetched than it might have once seemed.

“The pace of progress is most certainly accelerating,” said Dr. Jedd Wolchok, an oncologist and director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “There are so many things converging.”

In some cases, patients like Ms. MacKenzie with cancer that has spread inside their bodies — called metastatic disease — are able to stay alive much longer than previously predicted. Some are cured altogether by new drugs, a reversal of fortune that patients and doctors dared not contemplate just a few years ago. In a growing number of cases, patients with metastatic cancer are not cured but have access to so many treatment options that they are able to leap from one to the next, changing course whenever their cancer becomes resistant to a drug, always staying ahead of their disease.

This is a new paradigm. Until recently, the prevailing wisdom in oncology was that many early-stage cancer patients could be cured, but metastatic disease was almost always incurable. This thinking drove cancer research, treatment and care for decades. Oncologists often threw the kitchen sink at early-stage cancer patients, performing invasive surgeries and administering heavy doses of chemotherapy — which can make patients sick to their stomachs, prone to infection and bald, but can also have long-term side effects including infertility, heart damage, numbness in hands and feet, brain fog and fatigue. The belief was that the only chance to save the lives of such patients was to eliminate the possibility of their cancer’s spreading. Since metastatic disease was usually considered incurable, research focused on early-stage disease. For unfortunate patients who developed advanced cancer, care typically consisted of additional rounds of chemotherapy and palliative approaches. Now there is new hope for many of these patients.

It would be foolish to argue that we have the entire category of cancer in our cross hairs. Cures or long-term survival for certain types of the disease — like pancreatic cancer and glioblastoma, the form of brain cancer that killed Senator John McCain — are still stubbornly out of reach. For people with these and some other forms of cancer, the mortality rate has barely budged in the past 30 years. Researchers are working to change this through more laboratory work and research. More than 800 pancreatic cancer clinical trials are now recruiting patients across the country. And diseases like breast cancer — for which there are many new treatments and more every year — are still lethal for tens of thousands of people per year.

Outpacing cancer is currently within reach only for certain cancers and patients, but the lessons learned on these fronts are gradually being applied elsewhere. This is raising the possibility that at some point in the not too distant future, diagnoses of any kind of Stage IV cancer will dictate patients’ treatment, but not their fate. Or at least that’s the promise for those with access to the most cutting-edge science.

Right now, two relatively new classes of cancer drugs are displacing traditional chemotherapy for many types of cancer and giving metastatic patients, in particular, more time. Many of these advances employ a person’s own immune system to eliminate cancer cells, rather than using chemotherapy or radiation to do the extinguishing. These are modern immunotherapy drugs and antibody-drug conjugates, or ADCs.

The idea that the immune system could be harnessed to fight cancer is over a century old, but it took generations of painstaking laboratory research and experimentation to do so effectively. While one major, Nobel Prize-winning milestone came in the 1990s when scientists James Allison and Tasuku Honjo became the first to uncover the proper mechanisms, it took almost two decades before scientists and doctors translated the findings into drugs that could be prescribed to patients.

The job of the human immune system is to fight off harmful invaders, and it has checkpoints that stop it from attacking healthy cells. Cancer cells can disguise themselves as healthy cells and evade an attack by the immune system. “Checkpoint inhibitors,” a kind of immunotherapy, help the immune system to recognize cancer cells for what they are. The first blockbuster immunotherapy cancer drug, for melanoma, was approved by the Food and Drug Administration in 2011 and was followed by more new immunotherapy cancer drugs and combinations designed to treat many types of cancer. The drugs have extended the life expectancy for some metastatic cancer patients from months to years.

Former President Jimmy Carter, who turned 98 in October, announced in 2015 that he had metastatic melanoma that had spread to his brain. A decade ago, a patient like Mr. Carter would expect to die in less than a year, but he was treated with an immunotherapy drug called Keytruda, approved in 2014. It is one of the most successful immunotherapy treatments on the market and is useful for more than a dozen types of cancer. Mr. Carter entered hospice care earlier this year, eight years after his diagnosis of Stage IV disease.

In June 2022, researchers at Memorial Sloan Kettering Cancer Center and the department of pathology at Yale University School of Medicine unveiled the results of a rectal cancer study that used immunotherapy and put every participating patient into full remission, a staggering outcome. While the study was small and the patients need to be followed over time, the results — which experts have called “unheard-of” — are already giving researchers and pharmaceutical companies new ideas about how to leverage the approach for other patients.

ADCs, the other newer class of cancer drugs, work by combining antibodies that can find cancer cells with very strong chemotherapy drugs. An ADC is like a smart bomb that knows how to home in on a target without causing very much collateral damage. Patients can often stay on ADCs for a long time, even years or decades, unlike regular chemotherapy, which can often only be given for a short period because it’s too harsh on the body.

At least nine ADCs have been approved by the F.D.A. in the past five years, including one granted approval early last year after researchers published a trial showing that the drug could increase survival by nearly 50 percent for a large percentage of patients with metastatic breast cancer. When the study’s principal investigator presented the findings at a large cancer conference in June 2022, the doctors and scientists in attendance gave her a standing ovation. The new breast cancer medicine is a game-changer, and not a one-off. Rather, it’s a natural result of a new scientific understanding that is altering the futures of patients with many types of cancer.

The F.D.A. has long faced criticism for its slow pace of reviewing drugs for approval, but it’s moving faster than ever to get new drugs into the market. Between 2017 and 2021, it approved about three times as many new cancer drugs and cancer drug uses as it did between 2007 and 2011.

Carol MacKenzie is currently taking Trodelvy. In 2020 it was granted accelerated approval, which allows regulators to provide patients access to medicines based on fairly scant clinical data; it received regular approval a year later. She knows that Trodelvy may eventually stop working for her and hopes that by then there will be a variety of other drugs and drug combinations available or being tested in clinical trials that will accept her for enrollment.

“Each time that you have something new you wonder how many more things are there to try,” she said. It turns out the path to a cure may not necessarily require one miraculous new drug, but rather a constant flow of novel options to try. And in more and more cases, in this new age of cancer drugs and science, these options abound. But not for everyone.

The overall cancer death rate in the United States decreased by a third between 1991 and 2019, largely because fewer people smoke and develop lung cancer. As cancer screening, prevention and treatments for all types of cancer have improved, this decrease has continued and even accelerated. The national cancer mortality rate is falling by about 2 percent every year.

But despite these achievements, some 600,000 Americans still die every year from the disease, and glaring disparities in outcomes for different groups are stifling faster progress. The reality is that untold numbers of Americans are dying every year not because they have untreatable cancer, but because they cannot get the treatments that could save them. The Covid-19 pandemic helped expose the differences in health outcomes by race and drew renewed attention to the need to close those gaps.

For some of the most common types of cancer, the disparity in outcomes for whites and nonwhites is astonishing. Black women are less likely to be diagnosed with breast cancer than white women but are about 40 percent more likely to die of the disease. Black men are more than twice as likely to die of prostate cancer as their white peers. Some of these differences may relate to biology, as some groups are at higher risks for certain cancers, but a large percentage of cancer deaths among people of color are because of factors like lack of access to high-quality care, higher rates of chronic illness due to a variety of factors and structural racism built into the U.S. health care system.

It’s not just race. Wide disparities also exist between high- and low-income patients, those with health insurance and those without, people treated at academic medical centers where specialists are immersed in the latest research and people cared for by overworked doctors at community hospitals who may treat all types of cancer and are not as immersed in the latest science for each type. Ms. MacKenzie is white and being treated at Dana-Farber, one of the country’s best hospitals for breast cancer.”