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.
Is a Revolution in Cancer Treatment Within Reach?
by Kate Pickert
https://www.nytimes.com/2023/06/16/opinion/cancer-treatment-disparities.html
**
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 a series of eight drug regimens for her, 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 overexcited 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 multibillion-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 the scientists James Allison and Tasuku Honjo became the first to uncover the proper mechanisms, almost two decades passed 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, 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 result from 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.
“I can say to one of my patients who is well educated, relatively well off, ‘Listen, you’re going to do way better than the average,’” said Dr. Eric Winer, director of the Yale Cancer Center and a recent president of the American Society of Clinical Oncology, or ASCO, the world’s premier organization for cancer doctors and researchers. “The disturbing part of that is there are all these people who shouldn’t have to do worse than the average.”
Significantly narrowing disparity gaps would lower the country’s cancer death rate substantially without any new drugs or scientific breakthroughs. This is why the Cancer Moonshot, with its ambitious goal to cut cancer deaths by half, includes funding specifically to study and reduce racial disparities.
“We have to look at the differences in cancer biology by different races, but so much of this is access to care, having more advanced disease, not being on clinical trials, not having access to clinical trials, not having access to primary care physicians,” said Dr. Lori Pierce, a breast cancer radiation oncologist at the University of Michigan.
In 2020, Dr. Pierce became the first Black woman to serve as president of ASCO. During her one-year term and in the time since, she has focused on equity, particularly in clinical trials for new cancer drugs, where Black and Latino Americans are severely underrepresented. Although Black people make up nearly 14 percent of the American population, they account for just 3 percent to 6 percent of patients in cancer trials.
Underrepresentation in clinical trials matters. Without a representative sample of the population, it’s difficult to figure out whether new cancer drugs are equally effective (or ineffective) for patients of different races. And in this new age of cancer drug development, where metastatic cancer patients are moving from one treatment to the next, clinical trials are often the only way to get the latest medicines. Enrolling in trials may be, for some, the difference between life and death.
A long-held assumption in cancer care is that Black patients in particular are wary of enrolling in clinical trials, falsely believing that to do so means submitting to dangerous experimentation against their will. While there is some distrust — born of vile historical cases like the Tuskegee study — implicit bias exacerbates the problem: Health care workers often do not even offer Black patients the opportunity to consider participating in clinical trials.
Data presented at last year’s ASCO conference indicated that more than 80 percent of Black metastatic breast cancer patients are “somewhat or very likely” to consider participating in trials, but just half are aware that trials for their disease exist. Only about a third say they received all the information they wanted to make a decision regarding clinical trials. A meta-analysis published in the Journal of the National Cancer Institute in 2021 found that when offered the chance to enroll in clinical trials, Black patients participate at the same rate as white patients.
“Yes, there’s greater distrust among African Americans,” Dr. Pierce said. “Yes, there’s greater distrust among minorities, but if you communicate with them, they will go on trials at the same rate as people who are white. So the onus is on us as providers to create the environment and infrastructure so that we can present clinical trials to people of color.”
In January 2022, a federal law went into effect that could be a step forward. The law newly requires Medicaid, the public insurance program for low-income Americans, to cover routine medical expenses for clinical trial enrollees. Called the Clinical Treatment Act, the law could significantly increase nonwhite participation. (About 60 percent of Medicaid enrollees are nonwhite.)
Democratic and Republican lawmakers in the House and Senate introduced a bill in 2021 to further even out representation in clinical studies. Called the DIVERSE Trials Act, it would have provided incentives to diversify trials and circumvent a federal ban on compensating people for participating in trials so that people who may not be able to afford the transportation and child care required to travel to study sites can be reimbursed. One element of the bill, which encourages enrollment in clinical trials outside of major medical centers, became law in December. This should widen access to studies. The bill’s original sponsors said they planned to reintroduce the other provisions in the current congressional term.
Although new laws and advocacy can make the cancer care system fairer — and mortality differences by race are slowly narrowing — the explosion in sophisticated new cancer drugs is at the same time pushing things in the other direction.
“If you have no effective treatments for cancer, it doesn’t matter if you are a millionaire in the best health, because there’s no treatment,” said Dr. Lin, Carol MacKenzie’s doctor. “The more complicated it is to take care of somebody with cancer, the more inequities will appear. If you have treatments that depend on specialized testing and teams that are up to date on the most recent developments, there’s a lot more potential for inequity in outcome.”
When I wrapped up my own treatment for breast cancer in 2015, I was thrilled that the ordeal, which included surgery, chemotherapy, drug treatment and radiation therapy, was ending. But I was also terrified that my disease might return and turn fatal. “What if it comes back?” I asked my oncologist. Methodically, she listed all the drugs proved to work against the metastatic version of my type of breast cancer. She explained what drug she would administer first and what she would turn to if that medicine didn’t work. In the eight years since, even more medicines have come on the market. If my cancer returns, which is unlikely at this point, I will benefit from a wide array of drugs — many of which were approved in the past five years.
I am extremely fortunate, not just because of the drugs that exist for my type of disease, but also because I had the means to receive my cancer treatment at the University of California, Los Angeles, a large academic medical center. My oncologist is a top researcher who leads clinical trials and is well versed in existing and continuing science relating to my disease. I am also white and have high-quality health insurance. Many cancer patients in America are not so lucky.
Substantially reducing the scourge of cancer deaths in America depends on our ability to combine new cutting-edge science and drugs with a system that allows all patients to benefit from them equally. Focusing on one approach at the expense of the other will leave us stuck making steady but frustratingly incremental progress in the fight against cancer. We can do better.
To the Editor:
Kudos to Kate Pickert for her hopeful article, “Are We Learning to Outrun Cancer?” (Opinion guest essay, June 18). The answer is yes. I’m proof. Fourteen months ago, I was diagnosed with Stage IV metastatic colon cancer. Today, a year later, I am in full remission. Immunotherapy saved my life.
I’m 75, female and fortunate to live near the University of Michigan Rogel Cancer Center in Ann Arbor. In April 2022, an M.R.I. revealed a malignant “microsatellite unstable tumor” in my transverse colon. The tumor had spread to my lymph nodes, liver, peritoneum and lungs. I was told I probably had 2.5 years to live. I’d begin chemotherapy immediately.
Terrified, I switched oncologists. My new oncologist explained that my tumor qualified me for immunotherapy, not chemotherapy. Every three weeks, I was given IV infusions of Pembrolizumab, or “Pembro” (also known as Keytruda, the drug Ms. Pickert said reversed former President Jimmy Carter’s cancer). Eleven months later, after M.R.I.s and surgery, I was in full remission.
I never lost my hair, got nauseated, got burns on my skin, lost my sense of touch or poisoned other organs. My side effects were fatigue and slight brain fog.
Thank you for bringing these treatments to light, along with challenges in accessing them. This piece is essential to ignite new hope for survival.
Katherine Forsythe
Dexter, Mich.
To the Editor:
New treatments for cancer patients are giving the U.S. something we haven’t seen before: lung cancer survivors.
With many discoveries being made in lung cancer research, precision medicine has allowed us to drive treatment forward. A critical first step in precision medicine is biomarker testing, a method that identifies specific genetic “drivers” that cause cancer to grow and spread in different ways.
Take a teacher in Tennessee named Stephen Huff, who was diagnosed at 29 years old with stage IV lung cancer. Through biomarker testing, he was able to receive a targeted therapy for his specific mutation. Six years later, he’s continuing to live his life with his wife, child — and stage IV lung cancer.
A decade ago, treatment options were limited to surgery, chemotherapy and one targeted therapy, with a short-term life expectancy. Now, with the emergence of more than 50 therapeutic options, living longer and better after a lung cancer diagnosis is a reality for many patients.
We need to continue investing in research to revolutionize treatments to create a world where no one dies from cancer.
Upal Basu Roy
Bethesda, Md.
The writer is the vice president of research at LUNGevity Foundation, a lung cancer research nonprofit.
To the Editor:
As the bereaved parent of a child lost to cancer, I read Kate Pickert’s essay with great interest on Father’s Day. Ms. Pickert’s excellent essay closes by saying “we can do better” in ensuring that all patients benefit from breakthrough treatments.
The article, however, does not discuss the pediatric patient population. Cancer is the leading cause of death by disease among kids. Those fortunate enough to survive face a lifetime of physical and emotional challenges from the toxic treatments they endured.
Unfortunately, our nation’s commitment to pediatric oncology research does not match this devastating reality. Children are not little adults, and the drivers of their malignancies are entirely different than those of adults, so effective therapy demands a different approach. If there is a patient population desperate for less toxic, more effective treatments, it is our kids.
Too often, children are left behind because of the rarity of pediatric cancer. This needs to change. The revolution in next-generation therapies should prioritize children. They deserve nothing less.
Gavin Lindberg
Germantown, Md.
The writer is the president and co-founder of the EVAN Foundation, which supports research in neuroblastoma and pediatric cancer.
To the Editor:
While Kate Pickert points out many disparities in care and outcomes, she doesn’t mention a big factor tied to many revolutionary treatments: biomarkers.
Black women like me, for example, are more than 50 percent less likely to receive genetic and genomic tests to identify biomarkers for breast cancer that make us eligible for precision oncology clinical trials and lifesaving targeted drugs, such as antibody drug conjugates, which target specific tumor cells.
Precision oncology requires knowing the mutations driving a person’s breast cancer. Biomarkers are the key to unlocking cancer risks and treatment.
However, many nonwhite women, like me, aren’t being tested, so when a clinical trial is looking for women with a specific genetic mutation, we won’t know we are eligible because we don’t know that we have that mutation. When the latest lifesaving drug comes on the market, we won’t know if the drug is right for us because our biomarkers aren’t known.
As a unicorn — a Black woman with metastatic breast cancer, former health care executive, clinical trial participant and beneficiary of biomarker testing — I know we need to make biomarker testing more accessible to change the trajectory for all women of color.
Laura Crandon
Clarksville, Md.
The writer is the founder and president of Touch4Life, a breast-health equity nonprofit.
To the Editor:
Kate Pickert’s essay highlights recent progress in drug development for metastatic cancer. But it doesn’t mention one of the most promising treatments for metastatic cancer: curative intent radiation therapy to all areas of known metastatic disease.
With the development of advanced radiation technologies capable of sparing normal tissues, many oncologists have started using involved site radiation for select patients with limited distant metastases. By safely administering radiation to all areas of known disease, usually in combination with systemic therapies, such as chemotherapy and hormonal therapy, previously incurable patients can now achieve deep or even complete remissions.
In my (Johnny’s) experience of treating 130 patients with limited metastatic disease from 2014 to 2021, 30 patients are not only alive, but also without evidence of disease. Radiation controlled the targeted tumors in more than 90 percent of patients with minimal toxicity.
Combining metastasis-directed radiation therapy with the diverse portfolio of promising cancer therapies highlighted in the essay may provide the optimal path toward achieving a revolution in cancer treatment instead of focusing on drug therapy alone.
Johnny Kao
Caleb Kao
Jericho, N.Y.
Johnny Kao is the chairman of radiation oncology and director of the Cancer Institute at Good Samaritan University Hospital. Caleb Kao helped analyze the data in this letter.