Axios AM Deep Dive: Cancer breakthroughs

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A flood of cancer drugs has entered the market over the last decade, and some have been game changers for treating the disease. 

However, most are yielding only incremental advances: They're important to patients, but may be ballooning the already enormous cost of cancer care.

Why it matters: Some experts argue that the financial incentives to develop drugs mimicking those already on the market are detrimental to patients because they divert resources from truly transformative discoveries.

What's happening: Immunotherapies — which harness a person's own immune system to fight cancer cells — have attracted the most attention. 

CAR-T therapies, which modify a person's immune cells to attack cancer cells, have been successful in treating some blood cancers and melanoma. Researchers are now trying to adapt them for treating breast, lung and other "solid tumor" cancers.

Checkpoint inhibitor drugs — like Keytruda and Yervoy — block specific proteins on the immune system's T cells so they can attack cancer cells. Several have been approved by the FDA to treat breast, cervical, colon and other cancers. 

Keytruda, for example, has significantly improved the survival rates of patients with non-small cell lung cancer, though it still hovers at just 23% over five years in patients who haven't previously received other treatments and is even lower in those who have.

Reality check: The treatments are expensive. They only work in some people — and it isn't clear why.

Combining different checkpoint inhibitor drugs or administering them alongside CAR-T and other therapies has yielded incremental advances.

By the numbers: The number of cancer drugs approved by the FDA rose from eight in 2009 to 57 in 2020, according to a study published in JAMA Network Open in December. 

But of the 332 approvals over those 12 years, only 16% were based on new drug approaches.

The rest were additional approvals of an existing drug or first approvals of a "me-too" drug that enters an existing class of treatment.

The big picture: The U.S. spends hundreds of billions of dollars on cancer care each year, a portion of which is paid out of pocket by patients themselves.

But experts question how much the last decade of advances have actually moved the needle.

The 92 new cancer drugs approved for the first time between 2000 and 2016 extended overall survival by a median of only 2.4 months — or 73 days, according to a 2020 study in JAMA Network Open.

“Patients need choices and the marketplace needs competition, but unfortunately so much of drug development is redundant without a meaningful improvement in outcomes or lower costs for patients," said former FDA deputy commissioner and NIH oncologist Anand Shah.

The other side: Pharmaceutical Research and Manufacturers of America, the drug industry trade group, said the studies “are biased and seem intended to diminish the massive progress that has been made in the last three decades to bring cancer deaths down and the incalculable value of the hope and extended life these treatments bring to people with cancer and their families."

Between the lines: Some of these approvals allowed new types of drugs to be used for different tumors, which is clearly meaningful to patients. And me-too drugs can also have value, like if they have milder side effects in a particular patient or are more convenient to administer.

But overall, even as the total number of drug approvals spiked each year, the portion of those drugs that were truly novel declined, according to the JAMA study.

Since blockbuster drugs are known to work on a particular target, companies "keep tweaking that pathway and coming up with variations on a theme, and that does come at the exclusion of other potentially novel targets," says Russell Pachynski, a professor of oncology at Washington University in St. Louis who specializes in prostate cancer.

Plus, me-too drugs don't drive down drug prices.

"When you’re getting to a 5th and 6th cancer drug in a class, you’re not addressing that unmet medical need, but you’re also not getting price competition. Multiple drugs in a class of cancer medications don’t lead to reduced prices," said Aaron Kesselheim, a professor of medicine at Harvard Medical School.

The other side: Although these new precision therapies are expensive and have had narrow success, the hope is they'll eventually offer a better approach than the current system of going through a list of treatment options to find one that works. 

"If it is effective, [CAR-T] is a one dose therapy — once and done," says Yvonne Chen, a scientist at UCLA who designs CAR-T cells. Factoring in the total cost of medical care, "it is far more economically efficient compared to having three, four, five lines of therapies that eventually fail or fail from that start."

What to watch: The pipeline of cancer drugs in development is enormous. Although many of them are variations on — and new combinations of — existing treatments, others could deliver the next big advances. 

Researchers are developing next-gen CAR-T therapies to try to target solid tumor cancers and reduce side effects. They're also working on off-the-shelf versions of the treatments that would potentially be less expensive.

Antibodies are being engineered to deliver a payload of drugs to tumor cells. Another class — called bispecific antibodies — binds both tumor and immune cells, bringing them in contact so the immune cells can do their job. 

Vaccines that use mRNA technology similar to that in some COVID-19 vaccines and neoantigens are also being studied to treat cancer.

1. The search for next-generation cancer treatments

Some are game changers, but many are yielding incremental advances at best.

Deep Dive - Cancer

A flood of cancer drugs has entered the market over the last decade, and some have been game changers for treating the disease. <ul><li>However, most are yielding only incremental advances: They&#x27;re important to patients, but may be ballooning the already enormous cost of cancer care.</li></ul>

The U.S. faces a range of health care flashpoints — unaffordable drugs, opioids, vaping — as we debate whether to adopt universal care. For now, the Affordable Care Act is the law of the land, but Republicans want to issue it a final death blow.

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A look at the scientific breakthroughs changing the world, explorations in space and in worlds beyond our own and the threats posed to us by our own planet, both out of our control and of our own making.

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Data: Journal of the National Cancer Institute; Chart: Jared Whalen/Axios

Death rates for many individual cancer types, such as melanoma, have seen historic drops in the last decade. 

At the same time, a few cancers like pancreatic cancer have remained stubbornly unchanged. Others like colorectal cancer have even seen worrisome increases.

The big picture: Between 2000 and 2021, cancer death rates in the U.S. dropped 27%, from 196.5 to 144.1 deaths per 100,000 people.

Much of that progress occurred since the human genome was sequenced, allowing major changes in how we understand cancer, screen for it, and ultimately treat it with personalized therapies, experts say.

Where the advent of immunotherapies expanded treatments, there's been particular success with some lung and blood cancers and melanoma, said Karen Knudsen, CEO of the American Cancer Society.

There's also been a reframing of the goals in cancer treatment from curing the disease at any cost to preserving a patient's quality of life.

"The goal is to turn cancer into a chronic disease rather than a fatal one," Bryan McIver, the Moffitt Cancer Center's deputy physician-in-chief, told Axios.

Yes, but: There's still a lot of work to do. Cancer was the second leading cause of death after heart disease in 2020, killing 602,350 people. (COVID-19 was the third leading cause of death, according to the CDC.)

Here's what the experts told Axios about progress on a few major types of cancer:  

Lung cancer: It's still the number one cause of cancer deaths, accounting for roughly 136,000, or about 23%, of cancer deaths in the U.S. in 2020, per CDC data.

Yes, but: There's real progress. Certain types of lung cancer are highly receptive to immunotherapy and can be managed with an oral pill, McIver said.

Effective prevention strategies, like getting people to stop smoking and screening for those at higher risk, are gaining traction — although too slowly, Knudsen told Axios.

"For lung cancer, early detection can make quite a difference," Knudsen said — but she noted that the screening uptake for lung cancer is low. "It's a screaming call to action."

Colorectal cancer: This is the second most common cause of cancer deaths in the U.S., making up roughly 52,000, or 9%, of cancer deaths in 2020.

But while incidence is becoming less common for those over 50, there's been an increase in early-onset colorectal cancer, leading the U.S. Preventative Services Task Force to lower the recommended age of first screening from 50 years old to 45 last year. 

These people under 50 "are more likely to be diagnosed with advanced disease, which is concerning because we don't fully understand the reason why," Knudsen said. Researchers are examining whether factors such as diet, bacteria in the gut and inflammation might be factors.

"We need to better understand what it is that is different about the very youngest patients," Kimmie Ng, director of the Dana-Farber's Young-Onset Colorectal Cancer Center, told Axios in October.

Breast and prostate cancer: Female breast cancer and prostate cancer in men are the fourth and fifth leading causes of cancer death in the U.S. (Both come after pancreatic cancer, which had "disappointingly" few advances, according to McIver.)

One of the biggest steps forward in breast cancer was the recognition that there are at least five different subtypes with different genetic drivers, which therefore need different and more targeted treatments.

"The parallel cancer with which we haven’t had the same success is prostate cancer," Knudsen said. Different subtypes haven't been discovered in the same way, and while it has a high chance for being cured when caught at an early stage, screening remains low. 

It's particularly troublesome because certain ethnic groups, such as African American men, who are at higher risk for prostate cancer are less likely to catch it early. "We've still got to work on making access to screening more widely available," McIver said. 

Melanoma and cervical cancer: There were an estimated 6,900 deaths in the U.S. from melanoma in 2020. But with melanoma death rates declining an average of 7% per year for adults younger than 50 between 2013 and 2017, it's become a poster child for progress. 

"In the past, if you had Stage 4 malignant melanoma, your survival was measured in months and all the chemotherapy we could throw at you wouldn't extend that life," McIver said.

With forms of immunotherapy, patients have gone into "complete remission" for years, McIver said. "It's truly transformational stuff." 

Knudsen also attributes the drop in deaths to a steady reduction in incidence since 2005, attributing this to preventative steps like sunscreen use.

Another potential success story: The effectiveness of the HPV vaccine as a "cancer vaccine," Knudsen said. "If we hit the expected potential uptake in HPV vaccination, we will all but eliminate cervical cancer and about 50% of head and neck cancers," she said.

The bottom line: "The pattern of cancers have continued to evolve over time and some of it is about the environment we live in and the habits that we have," McIver said.

 There's still a lot to be optimistic about, but there's a lot of work to be done, he said.

2. The fast-changing survivability of cancer

Historic drops for some cancers, like melanoma, while others are unchanged or getting worse.

Death rates for many individual cancer types, such as melanoma, have seen historic drops in the last decade. <ul><li>At the same time, a few cancers like pancreatic cancer have remained stubbornly unchanged. Others like colorectal cancer have even <a class="gtmContentClick" data-vars-link-text="seen worrisome increases" data-vars-click-url="https://www.axios.com/alarming-trend-in-colon-cancer-cases-under-35-73dc64df-73ae-4fde-8050-5356aeab1582.html" data-vars-item="in_content_link" href="https://www.axios.com/alarming-trend-in-colon-cancer-cases-under-35-73dc64df-73ae-4fde-8050-5356aeab1582.html" target="_self">seen worrisome increases</a>.</li></ul>

The pandemic disrupted cancer treatments for millions of Americans, but it led health care providers to speed up efforts to shift care from hospitals and clinics to patients' homes.

Why it matters: Cancer patients at higher risk for infections and other complications could benefit from therapy and testing at home — and the care delivered in less intensive settings could also be cheaper. 

The big picture: The pandemic delayed cancer screening, treatments and rehabilitation while causing supply shortages and diverting medical staff. Many patients fearing COVID-19 stayed away from clinics as their cancers worsened.

There were an estimated 9.4 million missed cancer screening tests in 2020, per JAMA Oncology. The National Cancer Institute estimates there could be 10,000 more deaths from breast and colorectal cancers because of missed screenings.

Faced with staffing shortages and an influx of COVID patients, medical systems began shifting minor cancer procedures — like diagnostics or installing chemotherapy ports — out of hospitals so they could reserve wards for the more complex cases. 

Doctors turned to telemedicine and remote home monitoring to reduce travel and the risk of infection for patients like those with blood cancers or bone marrow transplants.

"What you’re seeing even in big cancer centers is movement to getting chemotherapy at home. A lot of things need to be figured out, but it’s already happening," said Arif Kamal, a Duke University professor of medicine and chief patient officer for the American Cancer Society.

Where it stands: The shift could continue after the pandemic ends. While cases are down and in-person screenings are picking up again, staffing shortages continue to cause delays at some infusion centers and can slow down getting second opinions and lab workups, clinicians say. 

Health workers quit in large numbers during the pandemic while many nurses moved to better-paying travel-nurse roles. That's left fewer experienced health care workers, especially in outlying areas.

"We're still addressing issues where departments are short staffed and the ability to accommodate patients along optimal timelines is challenging," said Dax Kurbegov, vice president and physicianin chief of clinical programs at Sarah Cannon, the Cancer Institute of HCA Nashville.

The bottom line: The post-pandemic landscape may be built around providing more care outside big medical centers and expanded outreach by advocacy groups and physicians to get patients screened on time.

3. How COVID reshaped cancer care

It was disruptive, but it sped up the shift to care in patients' homes.

Illustration of an IV bag surrounded by abstract shapes and abstract covid cells.

Coronavirus

The pandemic disrupted cancer treatments for millions of Americans, but it led health care providers to speed up efforts to shift care from hospitals and clinics to patients&#x27; homes.Why it matters: Cancer patients at higher risk for infections and other complications could benefit from therapy and testing at home — and the care delivered in less intensive settings could also be cheaper.

Algorithms are increasingly being put to work alongside radiologists and pathologists to help detect and diagnose cancers.

Why it matters: AI developers say these tools can help relieve a stressed health care system and improve critical medical decision-making, but experts caution about the risk of overdiagnosis that could drive up health spending and bring the possibility of unnecessary, risky biopsies.

Some also warn it's too soon to say whether the tools are effective.

Where it stands: Since the FDA began regulating algorithms as medical devices a few years ago, there's been a surge in computer models developed to help detect and diagnose cancer and to assist in prioritizing the workflow of radiologists. 

Last year, the FDA cleared an AI tool that sorts prostate biopsy images based on the odds of suspected areas being cancerous tissue for a pathologist to review — a first for cancer pathology.

Paige, the company that developed the tool, says the AI decreased errors in prostate biopsies by 70% in a study that is under review for publication. 

PathAI, Nucleai and other companies are also developing AI-based pathology tools. And the FDA has given clearance to other algorithms that assist radiologists in analyzing mammography and colonoscopy images as well as CT scans.

The next frontier for AI in cancer pathology is to use biological markers "to predict a clinical outcome that we don't easily predict today," says David Klimstra, the chief medical officer and co-founder of Paige. 

That could include predicting the risk of recurrence or the likelihood that a cancer will respond to a particular drug.

Keep in mind: FDA clearance is a lower bar than FDA approval when it comes to medical devices, including AI.

Yes, but: There is a risk of false positives and unnecessary treatment.

And if AI identifies something as suspicious, it can raise a red flag to a patient, which can cause anxiety, and potentially spur a risky biopsy that is unnecessary, says Jae Ho Sohn, an assistant professor of radiology at the University of California, San Francisco.

"But if AI is used well, it reduces false positives and false alarms."

Others argue that though AI tools may work well in testing, their effectiveness in larger, diverse populations is still not known. As algorithms are being integrated into cancer care, they are undergoing post-market surveillance. 

What they're saying: Recent surveys suggest people are comfortable with AI being involved in making clinical decisions but only if human clinicians have input.

What to watch: The next five years will be a transition period to a time when "every radiologist will use some sort of AI," Sohn says.

4. Meet the new AI cancer detectives

Algorithms are helping radiologists and pathologists detect and diagnose cancers.

Illustration of a motherboard with a heart monitor surrounded by shapes.

Algorithms are increasingly being put to work alongside radiologists and pathologists to help detect and diagnose cancers.Why it matters: AI developers say these tools can help <a class="gtmContentClick" data-vars-link-text="relieve a stressed" data-vars-click-url="https://news.harvard.edu/gazette/story/2020/11/risks-and-benefits-of-an-ai-revolution-in-medicine/" data-vars-content-id="155b578b-5f9e-437d-a09c-411a9b9d28a4" data-vars-headline="Meet the new AI cancer detectives" data-vars-event-category="story" data-vars-sub-category="story" data-vars-item="in_content_link" href="https://news.harvard.edu/gazette/story/2020/11/risks-and-benefits-of-an-ai-revolution-in-medicine/" target="_blank">relieve a stressed</a> health care system and improve critical medical decision-making, but experts caution about the risk of overdiagnosis that could drive up health spending and bring the possibility of unnecessary, risky biopsies.

Data: Fu, et al., 2022, “Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer"; Chart: Kavya Beheraj/Axios 

Health disparities among cancer patients — a known ongoing issue in America — were exacerbated by the COVID pandemic.

The latest: A study out earlier this week of 3,506 cancer patients shows "significantly higher COVID-19 severity" among African American than white cancer patients, bolstering similar findings from an earlier 2020 study of 73.4 million electronic health records.

Black cancer patients also experienced delays in radiotherapy sessions and in access to novel anti-COVID therapies like remdesivir — instead often receiving hydroxychloroquine, later found to be ineffective. 

"Unfortunately, if these same racial inequities in access to medical care hold for cancer screening, in the near future, we are likely to see worsening disparities in rates of advanced stage cancers at diagnosis," the co-authors wrote.

Between the lines: Many factors play a role in why people of different racial and ethnic backgrounds face disparities in the diagnosis and treatment of cancers. They can be affected by differences in income, access to health care, diet, environment, and genetics.

Among the biggest disparities: higher numbers of aggressive prostate cancer in African American men, liver cancer in Latinos, certain breast cancers in African American women, and certain esophageal cancers in white Americans and African Americans.

Genetics may play a large role, but that's not the only driver of the differences.

For example, hepatitis C, which can lead to liver cancer, was rising in multiple populations. Once an effective treatment was released, liver cancers dropped for those populations who could afford it, Marcia Cruz-Correa, physician-scientist at the University of Puerto Rico Comprehensive Cancer Center, tells Axios.

But "once we started to realize there was a disproportional access for one group of people versus the other, then health policy came into place" as Medicare, Medicaid and other insurance systems started to cover the expensive hepatitis C drug.

That helped alleviate the disparity in the Hispanic community, said Cruz-Correa, who also is a member of the American Association for Cancer Research board of directors.

"A large problem is that on average less than 5% of clinical trial participants are from a diverse population," Cruz-Correa says. 

For diseases that have a higher prevalence in certain populations, there should be an FDA policy to require participant representation of at least that level of proportion in the trial participants, Cruz-Correa says. 

"It's not an accident that those same populations who are underrepresented in these studies are also from many of the groups with the worst outcomes," says William Oh, an oncologist and chief medical science officer at Sema4, a health intelligence company.

Sema4 aims to enroll 5,000 advanced-stage cancer patients from diverse populations in comprehensive genetic and genomic testing.

What's next: Besides improving representation in trials, students of color need to be enticed to health care, and diverse populations should be targeted in the collection of Big Data that informs therapeutic and other research, says Karriem Watson, chief engagement officer of NIH's All of Us research program.

The All of Us research program is collecting health data from 1 million participants, primarily from underrepresented backgrounds, because "representation matters when you think about genomics and precision medicine," Watson says.

The power of massive databases and trials to unlock precision medicine

Cancer death rates drop but Black Americans still face highest risk

Pandemic may drive up cancer cases and exacerbate disparities

5. The pandemic made cancer disparities worse

"[W]e are likely to see worsening disparities in rates of advanced stage cancers at diagnosis."

Health disparities among cancer patients — a known <a class="gtmContentClick" data-vars-link-text="ongoing issue in America" data-vars-click-url="https://cancerprogressreport.aacr.org/wp-content/uploads/sites/2/2021/10/AACR_CPR_2021.pdf" data-vars-item="in_content_link" href="https://cancerprogressreport.aacr.org/wp-content/uploads/sites/2/2021/10/AACR_CPR_2021.pdf" target="_blank">ongoing issue in America</a> — were exacerbated by the COVID pandemic.The latest: A <a class="gtmContentClick" data-vars-link-text="study" data-vars-click-url="http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2022.4304" data-vars-item="in_content_link" href="http://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2022.4304" target="_blank">study</a> out earlier this week of 3,506 cancer patients shows &quot;significantly higher COVID-19 severity&quot; among African American than white cancer patients, bolstering similar findings from an earlier <a class="gtmContentClick" data-vars-link-text="2020 study" data-vars-click-url="https://jamanetwork.com/journals/jamaoncology/fullarticle/2773500" data-vars-item="in_content_link" href="https://jamanetwork.com/journals/jamaoncology/fullarticle/2773500" target="_blank">2020 study</a> of 73.4 million electronic health records.

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All-Access Weekly Digest

Particularly common among cancer patients, "financial toxicity" is a term that's used to describe the financial strain of paying for expensive medical care. Financial planners may be the solution.

Why it matters: Patients that received financial guidance or financial assistance have a higher survival rate, according to a 2020 research study — meaning relieving crushing financial burdens may have also improved their medical outcomes.

Even when they have health insurance, cancer patients still face out-of-pocket costs — like copayments and deductibles — that can add to the emotional stress of fighting cancer, especially if they don't have a financial safety net.

The study was presented by Thomas G. Knight of the Levine Cancer Institute to the 2020 American Society of Hematologists through a grant from the Foundation for Financial Planning's Pro Bono for Cancer Campaign. 

What they did: The pilot study consisted of 105 high-risk patients who were diagnosed with blood cancers and screened positive for financial toxicity, Knight tells Axios. 

Over six months, 59 patients received the three-step intervention. 

The first step was with a nurse addressing care, by identifying any gaps and potential grants to cover costs. The second was with a pharmacist reviewing the costs of medications and considering alternative treatments or medications. The final intervention was with a community pro-bono financial planner.

The remaining 46 patients were supposed to get the intervention, but the study was stopped early due to the start of the COVID pandemic.

What they found: The intervention group had better overall survival rates than those in the standard group. 

After six months, overall survival was 81.4% for the intervention group, compared to 73.9% in the standard care group.

At the 12-month mark, overall survival was 73% for the intervention group, and 46.4% for the standard care group.

What's next: The pilot study showed how centralized financial support can help improve cancer care. The key is that the financial planners have to be members of the community themselves.

"We have to balance centralized financial navigation, while looping in folks with specialized local knowledge," Knight says.

6. The health benefits of easing cancer costs

One study suggests cancer patients who got help with "financial toxicity" had higher survival rates.

Illustration of abstract shapes and dollar bills.

Particularly common among cancer patients, <a class="gtmContentClick" data-vars-link-text="&quot;financial toxicity&quot;" data-vars-click-url="https://www.cancer.gov/about-cancer/managing-care/track-care-costs/financial-toxicity-pdq#:~:text=pay%20your%20bills.-,Financial%20toxicity%20describes%20problems%20a%20cancer%20patient%20has%20related%20to,financial%20problems%20for%20a%20patient." data-vars-content-id="767870b2-a162-45bf-9596-9484689b67e4" data-vars-headline="The health benefits of easing cancer costs" data-vars-event-category="story" data-vars-sub-category="story" data-vars-item="in_content_link" href="https://www.cancer.gov/about-cancer/managing-care/track-care-costs/financial-toxicity-pdq#:~:text=pay%20your%20bills.-,Financial%20toxicity%20describes%20problems%20a%20cancer%20patient%20has%20related%20to,financial%20problems%20for%20a%20patient." target="_blank">&quot;financial toxicity&quot;</a> is a term that&#x27;s used to describe the financial strain of paying for expensive medical care. Financial planners may be the solution.Why it matters: Patients that received financial guidance or financial assistance have a higher survival rate, according to a 2020 <a class="gtmContentClick" data-vars-link-text="research study" data-vars-click-url="https://www.sciencedirect.com/science/article/pii/S0006497118708690" data-vars-content-id="767870b2-a162-45bf-9596-9484689b67e4" data-vars-headline="The health benefits of easing cancer costs" data-vars-event-category="story" data-vars-sub-category="story" data-vars-item="in_content_link" href="https://www.sciencedirect.com/science/article/pii/S0006497118708690" target="_blank">research study</a> — meaning relieving crushing financial burdens may have also improved their medical outcomes.

The fast-changing survivability of cancer

Abstract cancer ribbon surrounded by shapes and lines.