George Sheehan, 77, of Diamond Springs, California, enjoyed excellent health until he was stricken with a persistent sore throat in 2016. His ear, nose and throat specialist diagnosed the problem as acid reflux, but after months of treatment with traditional therapies brought no relief, Sheehan sought a second opinion from his gastroenterologist. Sheehan was referred to the University of California, Davis, where a biopsy confirmed that the retired manager had stage 4 squamous cell carcinoma of the larynx.

“They sat me down, explained I had cancer and said it would be best if they removed my larynx,” Sheehan recalls. “The cancer was isolated so I didn’t need chemo- therapy or radiation. I was very fortunate.”

Sheehan received a voice prosthesis and met regularly with a speech therapist. At the same time, Sheehan’s wife, Paula, also a cancer survivor, learned from visiting nurses and instructional videos how to help her husband keep his stoma clean and regain his ability to speak. When Sheehan was well again, the couple celebrated with a cross-country motorcycle trip.

Despite losing his larynx, Sheehan was luckier than many patients with cancer his age. Geriatric patients with cancer, defined as those 65 and older, often have health and other issues that can make cancer treatment difficult. Caring for this population has always been a challenge, but cancer care specialists are making strides to ensure that they receive the same level of support provided to younger patients.

Cancer can strike at any age but is most prevalent among adults as they age. According to a 2008 study published in the journal Cancer, about 60% of cancer incidence and 70% of cancer mortality occurs among adults aged 65 and older. This also happens to be the fastest-growing population in the United States, notes the National Cancer Institute, with a projected population of 84 million by 2050.

As patients age, they can be divided into three groups, says Dr. Stuart Lichtman, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. The first is the well elderly, who tend to be the minority. This is followed by the vulnerable elderly, who can be well functioning and independent but have other medical issues that make them vulnerable to side effects of cancer treatment. The third group is the frail elderly, such as patients in nursing homes. Some frail elderly patients are strong enough to receive treatment for their cancer, Lichtman says, but others may be so vulnerable that treatment is not even a consideration.

“Medicine is never black and white,” Lichtman notes. “You can’t just look at age. You have to look at the whole patient. Geriatric oncology is ‘the ultimate in personalized medicine’ because everyone is a little different. Everyone at that point in their life has had issues in the past and it affects treatment decisions as well as wishes and goals.”

Only within the past few decades has a greater focus been placed on the unique needs of aging patients with cancer, thanks to the efforts of advocates such as medical sociologist Rosemary Yancik, who served many years at the National Institutes of Health and was instrumental in founding the International Society of Geriatric Oncology in 2000. One of the most important concerns for advocates such as Yancik has been the lack of patients 65 and older enlisted in clinical drug trials because of safety concerns.

“In the early days of cancer treatment, the thinking was that people above the age of 65 would not be able to tolerate treatment, so the upper age was 65 for clinical trials,” notes Dr. Martine Extermann, program leader in the senior adult oncology program at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. “Dr. Yancik pushed for programs designed to help older cancer patients, and one of the first in the United States was here at Moffitt.”

A lack of aging trial participants can have serious consequences in cancer treatment, says Dr. Supriya Mohile, a geriatric oncologist at the University of Rochester Cancer Center in New York. “The challenge for us as oncologists is that data regarding the safety and efficacy of therapeutics comes from clinical trials that do not include older adults to the prevalence they have in the community,” she explains. “The therapies we have are tested on patients who are younger and in better health. When we see older adults who may have other health problems, we often don’t know how to appropriately manage that patient because we don’t have the data.”

Thankfully, attitudes regarding the inclusion of aging patients in clinical trials are starting to shift. The Cancer and Aging Research Group, in collaboration with the National Institute on Aging and the National Cancer Institute, reviewed gaps in knowledge about the care of patients age 65 and older with cancer and developed a series of recommendations to improve their participation. They include the following:

design trials specific to this patient population;

modify trial designs to collect more data on aging patients;

leverage population cohort studies to answer commonly posed questions in geriatric oncology regarding the feasibility, dosing and toxicity of a selected regimen;

conduct concurrent differential dosing trials for these patients; and

Ed Cutler, 75, of Tampa, Florida, after standard-of-care chemotherapy for 16 months, participated in two separate phase 1 immunotherapy trials as part of his treatment for lung cancer with metastases to the liver. The first drug combo — Imfinzi (durvalumab) and tremelimumab, two drugs known as checkpoint inhibitors, beginning in 2015 — reduced the size of the tumor in Cutler’s lung by 70% but side effects including severe colitis forced him to stop after seven months. A year later, Cutler began receiving taminadenant, another immunotherapy drug known as an adenosine receptor antagonist, in a phase 1 trial conducted at the Moffitt Cancer Center, again with positive results.

“I’m still an active participant of the trial and have been stable since early 2017,” Cutler says. “I am not cancer free. There is still something there, but it is not growing and it’s not getting any smaller. The treatment appears to be keeping my cancer stable.”

Cutler says that, to the best of his knowledge, his age was never considered a factor by his care team, likely because he was in relatively good physical health at the time with no comorbidities.

But that’s not the case for the majority of aging patients with cancer. Comorbidities tend to become more common with age and are a very important factor when developing a treatment plan. Especially concerning are illnesses that can negatively affect treatment and recovery such as obesity, diabetes, kidney disease, liver disease and heart issues.

“From a physiologic point of view, 20-year-olds are essentially the same. Everyone is healthy with no other diseases,” Extermann explains. “That changes as we get into our 70s and 80s. We need to understand the disease, but in addition, we need a knowledge of the patient that is much deeper than you would have for younger patients. We need to evaluate which diseases they have as well as their function and reserve, which is their capacity to rebound.”

One of the most useful tools available to geriatric oncologists is the comprehensive geriatric assessment (CGA), which helps determine if a patient will benefit from treatment or would be better off with palliative care. The CGA evaluates physical functioning, comorbid conditions, cognitive performance, psychological and nutritional status, social support, current medications and the presence of geriatric syndromes.

“With some patients, the screening may tell us that the patient is really very fit and should receive a full treatment,” Lichtman notes. “Another person may look pretty good, but when you start looking at their function, you discover all kinds of vulnerabilities, and if you start treatment with a full-dose regimen, you are going to harm that patient. We have to modify the dose and use a lighter treatment for the patient to get the best benefit.”

In a trial conducted by the University of Rochester Cancer Center, the CGA was found to improve care delivery and patient/caregiver satisfaction, Mohile reports. A second trial found that the tool also improves decision-making and reduces cancer treatment toxicity.

“We need to learn how to implement the comprehensive geriatric assessment better and make patients and care- givers aware of it,” says Mohile. “If patients demand this evidence-based practice of their doctors, practices will adopt it more.”

Home care — both during and after treatment — can present its own challenges for aging patients with cancer. Many require continued support from their medical team, which may include a home nurse, speech therapist, physical therapist, nutritionist, wound care specialist, social worker and others. However, daily assistance typically is provided by family and friends, which can result in caregiver burnout.

“Just because a patient is married, oncologists shouldn’t assume they have a caregiver because the spouse may be in worse condition than the patient,” Extermann says. “You have to ask patients about their arrangements.”

“Our system is not a good one for caregivers,” Mohile acknowledges. “We barely address caregiver needs in our clinical encounters, and there is not a lot of support for care- givers in general. This can affect the patient. If the caregiver is stressed or has their own health needs that are being affected by caregiving, the patient is not going to do well. We need to think about them as a team.”

Paula Sheehan did all she could to meet her husband’s care needs when he returned home from the hospital. Yet despite the support she received from nurses and others, she found the experience emotionally stressful. “I took it upon myself,” she says. “You have to learn how to care for your spouse when they get home, and it’s a shock, really. You have a lot on your shoulders. It was difficult, but we got through it together. I’m really proud of him.”

Numerous organizations provide resources for home caregivers including the American Cancer Society, the Cancer and Aging Research Group, the American Society of Clinical Oncology, Susan G. Komen for the Cure, the LUNGevity Foundation, the GO2 Foundation for Lung Cancer and the National Cancer Institute.

Aging patients are encouraged to be their own advocates and not hesitate to ask questions about their treatment options, goals and more. “One important question patients should ask is, what is the evidence for this treatment plan for patients like me? The doctor should be honest regarding the available data,” says Mohile.

Another essential question is how a particular treatment will affect the patient’s ability to function, Extermann adds. “Function matters a lot to older patients,” she notes. “Everyone wants to live longer but no one wants to grow old.”

Before surgery, patients and caregivers should look into appropriate support groups at their local hospital or cancer organization, Paula Sheehan suggests. “That was very helpful to us both,” she says. “Speaking with other laryngectomy patients before and after surgery helped us know what to expect.”

Cutler also encourages patients 65 years and older to talk not only to their medical care team but also to other patients with cancer who have been through it. “I think they are more valuable than anybody,” he notes. “A connection to other patients through the LUNGevity Foundation helped me personally and really began my journey of advocacy.”

While aging patients with cancer face unique challenges, it’s important to understand that treatment options are broad and the prognosis is good for most. “Nowadays, most cancers are either curable or manageable so that you can live several years with it,” says Extermann. “It’s not necessarily a death sentence.”

For more news on cancer updates, research and education, don’t forget to 

Articles

Features

As patients aged 65 or older receive a diagnosis of cancer, their treatment course and priorities may differ from their younger counterparts.

Treating Cancer as Patients Age

A cancer diagnosis can be overwhelming, leaving individuals with a flurry of emotions, concerns or even shock in the attempt to process the new direction their lives have taken. Support from family and friends becomes a crucial part of navigating the disease, though an equally important but overlooked need for many is the support and understanding from someone who has already walked the cancer path.

Finding someone who understands this experience firsthand, however, is not always easy. That’s why LUNGevity Foundation created the LifeLine Support Program.

The LifeLine Support Program is a free service that matches patients with lung cancer or caregivers with LifeLine Support Partners. The Support Partners volunteer to mentor and offer encouragement, advice, experience and hope to those newly diagnosed and anyone needing additional support through a one-on-one personal connection by email or telephone. Partners are matched based on factors such as type of lung cancer, age group or other similarities.

According to the National Cancer Institute, one in three people with cancer experiences mental or emotional distress, with a staggering 25% of cancer survivors experiencing symptoms of depression and 45% experiencing anxiety. LifeLine Partners can be a vital part of a newly diagnosed patient’s support system and can help navigate through the logistics and emotions of a lung cancer diagnosis.

“It’s like having a wingman who not only helps you in the beginning, but also helps you adjust to living with the disease,” says Michelle, a LifeLine Support Partner mentee. “You need that added support before the next round of labs or the next scan. You need to expect the unexpected and have the safety net. A LifeLine partner gives you that.”

It is LUNGevity’s goal to help mitigate the tremendous emotional pressure one faces upon and through their diagnosis. No one can understand the concerns of a patient with cancer on quite the same level as someone who has already had those same thoughts, feelings and experiences. LifeLine partners can offer help with the practical aspects of self-advocacy, communicating with your medical provider, how to share your diagnosis with your loved ones and what symptoms to expect. This peer-to-peer support can also address the emotional aspects of a lung cancer diagnosis; for example, how to use mindfulness practices to battle fearful or negative thoughts.

LUNGevity offers the largest online network of support and survivorship programs for all people affected by lung cancer. Our annual International Lung Cancer Survivorship Conference is composed of three summits that provide an opportunity for local communities to come together to find the latest information on treatments and living with lung cancer, as well as to be surrounded by other people impacted by this disease: the HOPE Summit for patients, the COPE Summit for caregivers and the Survivorship Summit for advocates and survivors who are interested in more advanced topics.

Patients and caregivers can receive additional peer-to-peer support and information from LUNGevity’s social media platforms as well as the online Lung Cancer Support Community, an extensive message board that includes the latest lung cancer information and notices of lung cancer events and advocacy opportunities. The Lung Cancer HELPLine also offers toll-free, personalized support for patients and caregivers at any time during their lung cancer experience. LUNGevity’s oncology social workers are available to individuals to manage their emotional, financial and support challenges.

Also provided are referrals to financial assistance resources for needs including pain medication, home care, child care, medical supplies, transportation for treatment and copayment assistance.

More than 235,000 people in the U.S. will be diagnosed with lung cancer this year, with a new diagnosis every 2.2 minutes, according to the National Cancer Institute. The road after a lung cancer diagnosis is often troubling, uncertain and difficult to navigate, and it is not uncommon to feel lost on the journey. But the road isn’t one that needs to be traveled alone. Support is always just a step — or a phone call — away.

Healing Well

Katie Brown, senior vice president of survivorship and support for LUNGevity Foundation, wrote about a program for patients to gain knowledge from survivors.

Peer Support Helps Patients Navigate Their Cancer Journey

in 2021, more than 200,000 new cases of melanoma are expected to be diagnosed, according to Aim at Melanoma. For all stages, the survival rates are estimated at 93% — and hope continues to rise among those with the disease as new therapies are under clinical evaluation.

In particular, treatment options that involve patients’ immune systems in attacking malignant cells continue to be expanded upon.

As part of its Speaking Out video series, CURE ® spoke with Dr. Sunandana Chandra, from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University
in Chicago, on behalf of Aim at Melanoma, about emerging therapies in the treatment of melanoma.

Q: Can you talk about what adoptive T-cell therapy is?

A: Adoptive T-cell therapy is a way of treating a person’s cancer with their own immune cells. It requires collecting and growing or expanding a patient’s own T cells. So the way that that’s accomplished is that a piece of the tumor — or melanoma in this case — is surgically removed and then processed at a separate facility or sometimes at the institution’s own facility. It’s processed at a separate location so that these immune cells in the tumor, known as tumor infiltrating lymphocytes, can be extracted and then expanded or grown. And what’s unique about those immune cells is that they have the ability to recognize that person’s own melanoma. So then the patient undergoes chemotherapy, and those expanded
T cells are then infused back into the patient, along with a few doses of this drug called interleukin 2, or IL-2. So that’s essentially what adoptive T-cell therapy is.

Where are we in evaluating these therapies like TIL?

The therapy is logistically a bit more challenging to administer. But this therapy is quite promising. It is important to note that it’s not yet (Food and Drug Administration [FDA]) approved.

What kind of data are we seeing with these therapies?

We are seeing that this is a very promising therapy for patients who have progressed on immunotherapy and/or a BRAF/ MEK therapy if they have a BRAF mutation. And if a patient is well enough to receive TIL therapy, then it is definitely another option for us, the medical oncologist, to consider for a particular patient. Now, not all patients may be eligible for TIL therapy based on certain clinical characteristics and tumor characteristics, but it’s certainly something that we could at least consider.

What do patients with melanoma have to look forward to in the treatment landscape?

In cutaneous melanoma, there’s a lot of new therapies that are being looked at to try to improve the patient’s survival outcomes. Newer agents that are being studied in addition to TIL therapy are ones that target LAG-3, TIGIT — this class of oral drugs called tyrosine kinase inhibitors. And all of these that I just mentioned can be used in combination, we think, with our existing immunotherapy drugs. 

And so that’s being actively studied in clinical trials. And in addition, other options such as immunomodulators, or drugs that tweak or affect the immune system, such as STING agonists, toll-like receptor 9 agonists may also affect the immune system in a positive way that ultimately lead to cancer cell death.

That sounds like a lot to look forward to.

Absolutely, I mean, in general, we are trying to use combination approaches either with our existing FDA-approved drugs or new drugs all together that target different proteins to ultimately try to cause melanoma cell death.

Speaking Out

In its Speaking Out video series, on behalf of Aim at Melanoma, CURE ® spoke with Dr. Sunandana Chandra about emerging therapies in melanoma.

Aiming for New Targets: Emerging Therapies in Melanoma

Pet companionship — regardless of the animal — can mean a lot to people, especially during turbulent times in their lives such as receiving a cancer diagnosis and undergoing treatment. It is common for patients to show photos of their pets to nearly everyone and treat them similar to their children. Pets can play an integral role in patients' lives.

For patients with cancer, pets can also motivate them to exercise and bring positivity to their lives.

“Sometimes taking care of a pet offers certain demands, and sometimes they can be a challenge, but many patients do talk about the positive aspects (of pet companionship) and how having a pet pushes them to be more active and also brings some joy to their lives,” said Dr. Aminah Jatoi, an oncologist and the Betty J. Foust, MD, and Parents’ Professor of Oncology at Mayo Clinic College of Medicine and Science in Rochester, Minnesota, in an inter- view with 

The benefits of pet companionship during cancer treatment have been a focus of research for years, including one study reporting results of a survey completed by patients with cancer during chemotherapy published in the 

in 2010. Researchers aimed to assess the benefits and potential negative effects of pet ownership in these patients, such as who would care for a patient’s pet if their cancer worsened, for example.

“It really surprised me and ... surprised everybody else on our team. What we learned was that it wasn’t a sense of worry,” Jatoi said. “In fact, the majority of people who were part of that study said that they had contingency plans for their pets. They had plans in place (for) if (patients) didn’t do well (from their) cancer ... which made me think that if it is a source of stress, people have cared so much about their pets that they’ve made it so that their pets would be taken care of. ... I think it really showed that pets mean an awful lot to people who have cancer.”

The type of pet a person has — dog, cat, lizard, horse or other animal — may not indicate the benefit one may obtain from their companionship, and Jatoi noted that not every person will be suitable for a pet.

“It’s probably very person-specific,” she said. “There are probably some people for whom having a pet is just not the right thing to do. You certainly don’t want to figure that out the hard way and then have to give up on that pet.”

For patients who enjoy the companionship of a pet but cannot have one because of their living arrangement or other circumstances, some institutions including Mayo Clinic have pet therapy programs. Jatoi mentioned a former patient who was depressed from a prolonged hospital stay and wouldn’t speak much to the staff. With the help of a dog named Jack, who also has a book written about him, Jatoi said this patient became a new person.

“I remember the first day after (Jack) entered that room, the whole ambiance ... changed,” Jatoi recalled. “The drapes were open. The patient was smiling. He was so much more interactive than he had been, and I know Jack made a huge difference.”

Jatoi said oncologists don’t typically ask about patients’ pets during visits or treatment.

“I think the message there is that we, as cancer health care providers, maybe don’t focus as much on pets and what they mean to patients as we probably should,” Jatoi said.

That doesn’t mean that all oncologists don’t ask about pet ownership. Jatoi recalled a now-retired doctor who would make notes about things that were very meaningful to patients, which was often their pets. He would go as far as to include the pets’ names so he would remember for the next visit.

“If it meant a lot to (patients), it meant a lot to him. We probably don’t do that enough,” Jatoi said.

Having a pet to care for may motivate patients to exercise and be positive when undergoing cancer treatment.

Pet Companionship During the Cancer Journey

As much as patients, their families and their caregivers want their cancer journey to take an overall positive trajectory, sometimes the odds are against them. This can set everyone’s mind racing with worries about what they need to take care of in their lives and how to remain as comfortable as possible as they reach the end of their lives.

Dr. Kashyap Patel, CEO of Carolina Blood and Cancer Care Associates in Rock Hill, South Carolina, and vice president of the Community Oncology Alliance, recently published the book “Between Life and Death: From Despair to Hope,” which focuses on his and some of his patients’ experiences as they come to terms with death.

“Patients don’t mind accepting the conversation about (dying),” Patel told 

. “What they don’t like is losing control. The happy medium of accepting (death) comes from being very transparent about our ultimate goals.”

In the book, Patel wrote about his experience with Harry Falls, a retired military pilot-turned-hang glider who received a diagnosis of stage 4 cancer. Patel and Falls formed a relationship that lasted until Falls died. Patel took notes of their meetings to formulate this collection of discussions.

“I thought if I can make this a conversational piece, jotting down my experiences with Harry and how I was able to prepare him (for death), I felt it probably may help many of my colleagues as well as patients to be ready for this conversation.”

Patel also detailed his time with another patient, Annie Carlson, a theater artist who received a diagnosis of advanced breast cancer in her mid-20s.

Both patients’ experiences with Patel highlight the importance of these connections with their health care teams during a terminal cancer diagnosis. Patel recommends that every patient or caregiver ask their oncologist very candidly about their life expectancy, which can sometimes be a frightening conversation, but can give a patient the chance to take control of their life.

“The (conversation after that) would be that ‘I want to live as long as I can, but I don’t want to lose my quality or dignity of my life,’” Patel said. “Life is all about balance ... allowing patients to have the liberty of conversation with the physicians that, ‘Please be honest with me, please make sure that you respect my cultural, spiritual or personal belief of how I want to be in control and how I want to leave this world with my terminal illness.’ I think that will alleviate lots of suffering.”

The end goal is not looking for a cure, but rather accepting that the advanced-stage cancer will be a life-limiting event, Patel said. He also emphasized the significance of focusing on quality of life during this time.

“How can we from now until the day (you die) maximize your presence on Earth for you, for your loved ones and for (people’s lives) that you can make a difference in?” he said.

Not only are patients a part of this process, but so are their caregivers, who play “a very vital role,” Patel said. Caregivers can offer patients the support and love they need to go through this time in their lives, which can include completing a bucket list with trips and activities the patients always wanted to do.

“In time, whatever time is left, we can make that person feel most relevant,” Patel said.

Caregivers can also empower the patient to “let go” during a time that can be the most frightening.

“Gently holding the hand and whispering in the ears of the loved one that we give you permission to move on wherever you’re heading, it’s actually quite soothing,” Patel said.

“The caregivers can be there to enable the patient who’s been going through these challenges of ensuring that whatever could be fulfilled within the narrow time frame can be achieved and accomplished.”

Patel added that we are mortal creatures, but it is up to all of us to decide whether we hide in a constant fear of death or accept it since it is inevitable.

“Accepting, compromising ... and living in equanimity — I call these three a foundation of being happy,” Patel said. “Accept what comes your way, compromise with what you have and make it to the fullest where you can have a quality of life combined with longevity if you can and then leave your life in equanimity so that you are not losing (the) pure emotional struggle by the fear of death.”

Bookshelf

Patients and their caregivers can navigate a terminal cancer diagnosis while keeping dignity intact.

Recognizing Cancer Fate Without Losing Control

Progress in treating mantle cell lymphoma (MCL) has allowed patients to weigh their options for first-line therapies. Despite this progress, disease progression or recurrence is still common in these patients, so patients must be aware of their quality of life when undergoing first-line and subsequent therapies.

During a presentation at the 2021 ASCO Annual Meeting, Dr. Brian K. Link professor of internal medicine-hematology, oncology and blood and marrow transplantation at the University of Iowa in Iowa City, discussed how we can “unquestionably” do better regarding first-line therapies for MCL and why research focusing on quality-of-life outcomes is critical. CURE® spoke with Link to learn more about why frontline therapy for this disease is important even though the order in which treatment is administered may not impact outcomes as much as researchers previously believed.

A: Mantle cell lymphoma is a serious disease. Most people, but not all, who are afflicted with mantle cell lymphoma will likely have their life shortened because of (the disease), and almost everybody will have their quality of life affected.

Invariably, for the vast majority of patients, we feel the need to alter that risk of suffering from lymphoma and/or dying from lymphoma by treating (it) with a variety of medical therapies. Surgery and radiation are not commonly part of the management plan. A high percentage of patients will have multiple courses of treatment intermittently over the course of their lifetime, and the first treatment chosen is generally what we refer to as upfront therapy.

Why may the upfront therapy patients receive be important to outcomes?

The outcomes for mantle cell lymphoma have improved substantially over the past 10 to 15 years. Two of the abstracts discussed at ASCO essentially started around 2010. Back in 2010, the prevailing evidence suggested that half of patients who were diagnosed with mantle cell lymphoma would die within the first four years. At that time, accordingly, the choice of which therapy to use first was critically important in an effort to mitigate that risk of early death.

In the subsequent 10 to 15 years, the likelihood of dying within four years has substantially reduced such that we now look at upfront treatment options for patients with mantle cell lymphoma with an eye toward what is likely going to be the second treatment and the third treatment since now more patients will be living five, 10 and 15 years. None of the treatments yet will result in (a) cure, so we still anticipate there will be multiple treatments over the course of a lifetime, and the choice of upfront treatment may not be as important as it was 10 years ago.

What are other takeaways from your presentation?

Because we now have many effective therapies, it’s important to recognize that
we as doctors do not agree on a one-size-fits-all (treatment). Thus, when patients ask “What’s the best treatment for me?” they should recognize (that) their doctor may not know of one single, best upfront therapy. They may know other patients with mantle cell lymphoma who are getting other choices for upfront therapy. They may get a second or third opinion from other doctors who may not all agree on what the best choice is for upfront therapy for them.

Patients need to recognize increasingly (that) they have a choice. Some of their choice will be philosophical. As a rule of thumb, some of the more aggressive treatments in the upfront setting may last a little longer but may involve more impact on their quality of life up front. For some patients, that may be appropriate. For other patients, they may prefer a gentler approach, recognizing that the effects may not last as long.

Because there are now so many treatments available, there is less critical importance, perhaps, on which therapy is given as first choice because the second, third and fourth treatments may have as much impact on their overall quality and duration of life as the first-line (treatment).

What is the impact to quality of life that patients may expect with these choices?

Some of the treatments require hospitalization to be administered. Others can be delivered as an outpatient basis. Some of the treatments are a little bit more intense but have a fixed duration of time, meaning three to six months of treatment and then there’s a cessation of treatment with observation. Other therapies are given chronically, often with oral medications, but sometimes intravenous medications, but the therapy goes on for a period of many years. Patients will want to assess how (they) feel about chronically being treated.

And then other things are more subtle, such as some of the treatments would cause cosmetic changes, such as hair loss, while others may result in fatigue, bowel irregularities, long-term risk of heart damage or rashes. There’s a whole variety of different side effects with the different therapies available, and patients should feel free to ask about all those options and then weigh for themselves which ones are least desirable.

During your presentation, you said MCL may be increasingly recognized as a chronic disease. What do you think this may do to the treatment of MCL or the research within this disease state?

I have fairly strong opinions about that because patients can now anticipate living a long time. Because they will have many treatment choices available to them, they’ll want to choose treatments that have an impact on something other than how long they’re going to live. We need to hear from the patients about what’s important there. Choices could include (that) they may prefer to have long periods of time where they’re not taking treatment, or it may include other elements of quality of life that we as clinical researchers and doctors can only really speculate about because we’re not the ones who are facing the decisions patients are. To the extent that patients want to have a role in shaping research moving forward, they should use patient-focused lymphoma societies such as the Lymphoma Research Foundation and advocacy groups to work with clinical researchers to develop quality-of-life outcomes in future research.

What’s an important message about MCL treatment that patients should know?

There is no one-size-fits-all in the upfront (setting), so patients will really want to be aware of that if they either seek multiple opinions from other doctors or if they seek other experiences from other patients.

(Also,) I want to emphasize that the choice of therapy that they make for first treatment is not as important as it used to be because there will undoubtedly be second treatments, third treatments and fourth treatments. We really don’t know the impact of sequence.

The last point I want to make is several of these choices would involve different short-term and long-term impacts on their quality of life and daily life. They’ll want to be aware of what their personal choices are when making these decisions and they’ll want to work with advocacy groups to build measurements of quality of life into the next generation of research trials.

Research News and Updates

Patients can now prioritize whether durable responses to treatment or avoiding certain side effects are more valuable to them. 

 ‘No One-Size-Fits-All’ First-Line Treatment for Mantle Cell Lymphoma

Drew Huggins was running out of options. After his diagnosis of metastatic pancreatic cancer two years ago, at age 47, he hadn’t had any luck with the treatments he’d tried so far.

His tumors didn’t respond to 13 cycles of FOLFIRINOX, an arduous four-drug chemotherapy combination. The chemo- therapy combination of gemcitabine and paclitaxel didn’t work either. They only left him with severe neuropathy, which causes debilitating pain, weakness and numbness in his hands and feet, from which he is still trying to recover. Next, he enrolled in a clinical trial at The University of Texas MD Anderson Cancer Center in Houston that used an antibody-drug conjugate to try to attack the tumor. But while Huggins was on this drug, the tumor grew by 25%.

“After that, I pushed and said, ‘There’s got to be something else that can be done here,’” Huggins recalls.

It’s rare for pancreatic tumors to have a genetic mutation that drugs can target. But Huggins’ oncologist took a “we’ll never know till we try” approach, and it paid off. The doctor sent tissue from one of Huggins’ tumors to a lab to see if it had any gene mutations that might be vulnerable to existing targeted drugs.

“And that’s when it came back with the match,” Huggins says.

Huggins’ tumor had a rare mutation called an NRG1 fusion. This genetic change happens in only about 1.5% of pancreatic cancers, according to some estimates. That gives NRG1-driven pancreatic cancers the distinction of being a “rare disease.” The gene fusion made Huggins eligible for a phase 1 clinical trial in MD Anderson’s Department of Investigational Cancer Therapeutics. The trial tests a targeted drug called Zeno (zenocutuzumab) in any type of cancer driven by NRG1 fusions.

Huggins travels the 200-plus miles from his home in San Antonio, Texas, to MD Anderson for two-hour infusions every two weeks. His first scan six weeks into the experimental treatment showed a significant reduction in tumor size.

“It was dramatic. On the scans, you could see the difference in the dark areas and the areas where it was cleared up,” Huggins says.

Now, nine months later and still on the treatment, his cancer is stable. 

Increasingly, researchers are playing matchmaker between patients with metastatic cancer and targeted drugs. In studies called basket trials, researchers focus less on the cancer site — such as the breast, lung or colon — and more on the genetic makeup of the tumor no matter where it first appeared. They perform comprehensive genetic analysis of the tumor tissue to see if it carries any tumor-driving mutations for which targeted drugs already exist. The existing drug may not be approved by the Food and Drug Administration (FDA) or may have approval to treat only a certain type of cancer with that particular mutation. But in the trial, anyone with that mutation, regardless of the type of cancer, receives treatment with that drug to see if it might work for them.

“Is treatment response guided more by the mutation or more by the tumor type? We are looking for the answer to that. The results may be complicated,” says Dr. Peter O’Dwyer, who co-chairs the NCI-MATCH trial, the largest-ever basket trial. The publicly funded trial is co-led by the ECOG-ACRIN Cancer Research Group and the NCI.

While basket trials won’t lead to effective new treatment options for everyone, the study design is bringing hope as well as life-prolonging treatment to many people who previously had none.

Targeted drugs, also known as precision treatments, attack a specific genetic characteristic of the tumor that is helping it grow. The drugs act more specifically on cancer cells, unlike chemotherapy, which attacks cancerous and normal cells. Typically, a specific genetic alteration or presence of a protein in the tumor would be necessary to be eligible for treatment.

Among FDA-approved targeted drugs are treatments for breast, colorectal, skin and lung cancers and many others. Typically, the FDA approves these drugs to treat a specific type of cancer, such as lung. Sometimes drugs earn approval for another type of cancer later, after additional studies prove it is beneficial for that other type.

Non-small cell lung cancer is one in which targeted drugs have been a major advance. There are nearly a dozen targetable gene mutations that arise in this type of cancer. Comprehensive biomarker testing matches patients or the genetic makeup of their unique tumor with treatments.

This type of genetic matchmaking is why Shyreece Pompey, 50, who now lives in Woodland, California, believes she’s alive today. She has been living with stage 4 non-small cell lung cancer for seven years.

When she was diagnosed with advanced cancer at a local community hospital in St. Joseph, Michigan, the oncologist wanted to start her on a highly potent combination of chemotherapy drugs that night, and Pompey agreed. But she also sought a second opinion on her treatment options at the University of Michigan.

“That’s where I learned about targeted therapy for my specific biomarker,” she recalled. “They never mentioned that at the other hospital.”

Pompey had ALK-positive lung cancer, so she received Xalkori (crizotinib), which targets ALK and ROS1 fusions. Her cancer didn’t progress for three-and-a-half years. But eventually, it spread to her brain. That’s when her oncologist switched her to a different ALK inhibitor called Alecensa (alectinib).

The drug shrank all her tumors. They are still visible but static. Today, her lungs, which were filled with fluid and caused her great difficulty breathing when she was diagnosed, have recovered their full capacity.

“My voice is hoarse this morning but that’s not because of the cancer,” she says. “I sang with the worship team at church yesterday. They like to have me rock out on this one rock-gospel song.”

Pompey’s story is not unusual. Though many life-prolonging targeted drugs are available to treat non-small cell lung cancer, comprehensive biomarker testing to match patients with those drugs is not a foregone conclusion at every health care facility. Some organizations, such as the American Society for Clinical Oncology, recommend that everyone with this type of cancer get tested for at least the most common drug targets. Some patient advocacy groups, such as the American Lung Association and LUNGevity, urge anyone with non-small cell lung cancer to ask their health care provider about comprehensive biomarker testing.

Non-small cell lung cancer is just one cancer type for which medical societies are pushing for doctors to let genetic mutations be their guide. But basket trials could prompt this type of paradigm shift across many cancer types and lead to more “tumor-agnostic” drug approvals from the FDA. That means the drug would be approved to treat any type of cancer, regardless of where it originated, as long as it has a particular genetic mutation.

“We have a few drugs that have tumor-agnostic approval, but so many other targeted drugs do not,” says Dr. Monica Mita, a hematologist-oncologist and co-director of experimental therapeutics at Cedars-Sinai Medical Center in Los Angeles. “That’s one of the most interesting opportunities of tumor-agnostic studies.”

Basket trials also give researchers the opportunity to learn the role that certain tumor-driving gene mutations play in the overall behavior of the cancer. “It’s an opportunity to go beyond just seeing the cancer as a breast cancer or a colon cancer and to see it instead, for example, as a PI3K-mutated cancer,” Mita says.

The greatest beneficiaries of this study design may be people with rare cancers.

Ann Rerat of Trumbull, Connecticut, learned she had leiomyosarcoma (LMS) of the uterus in 2017 when she was 60 years old. This rare but very malignant cancer can develop in any smooth muscle tissue, such as the digestive system, urinary system, blood vessels and uterus. Uterine LMS affects fewer than 1 in 100,000 women.

In cancers as rare as these, clinical trials are pretty uncommon. Researchers simply cannot enroll enough patients with the disease to study it properly. That’s why basket trials can be such a boon for people with these rare conditions. When researchers build study cohorts based on the genetic makeup of the tumor, rather than the tumor type, they may be able to enroll enough people with many different tumor types for a viable clinical trial.

After a hysterectomy, a targeted drug, an additional surgery and chemotherapy with docetaxel and gemcitabine, Rerat’s cancer continued to advance. She was at stage 4 and had a life expectancy of less than five years when Dr. David Hyman, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, invited her to participate in a basket trial. The JAVELIN BRCA/ATM trial tested the drug combo of the PD-L1 inhibitor Bavencio (avelumab) and PARP inhibitor Talzenna (talazoparib)
in people with advanced solid tumors that had either a BRCA1 or 2 gene mutation or an ATM mutation. Rerat was a match.

Talzenna is a daily pill and Bavencio is administered by IV infusion every two weeks. When Rerat started the drug combination in August 2018, she had tumors throughout her pelvic area. She went for scans every three months to monitor the drug’s efficacy.

On the first scan, the tumors were smaller. By the sixth, Rerat had no evidence of disease. Her scans have been clean ever since.

“I still don’t have the words to express what it was like to get those results,” she says. “Incredible. Grateful. It has changed my whole world.”

Basket trials may make this world-changing impact on many people with rare cancers.

“People with very rare tumors are an underserved population,” Mita says.

The DART trial aims to serve these patients. This trial tests the immune checkpoint inhibitor combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with any of a long list of rare solid tumors. A recent publication of the nonpancreatic high-grade neuroendocrine carcinoma group showed that 44% of patients with this type of tumor responded to the drug combo. In the angiosarcoma patient group, 25% responded.

As of June 20, 2021, about 60% of the 1,172 patients enrolled in the NCI-MATCH had rare or less common cancers. The trial defines “less common” as any cancers other than breast, colorectal, non-small cell lung or prostate. Among the less common cancers included in the trial are cancers of the central nervous system, kidney, liver and biliary tract, and neuroendocrine cells, among others.

“But you can also think of rare cancers as being defined by molecular aberration,” O’Dwyer says. “Some of these mutations occur in fewer than 1% or 2% of cancers, so in many regards each of these tumors is a rare tumor.”

That’s the case with the NRG1 fusions — the kind that Huggins has.

“NRG1 fusions are extremely rare; however, they are rare across many different disease types, so when you group them all together in a basket trial, you can study the effects of targeting this genetic alteration,” says Dr. Alison Schram, a medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator on the Zeno trial in which Huggins is enrolled. Schram and her colleagues recently reported that 42% of patients with NRG1 fusion-positive pancreatic cancer responded to the drug.

Tumor Type or Gene Mutation: Which Matters More?

For some, but certainly not all tumor types, basket trials have shown that mutations could be more important than tumor type in treatment decisions. Basket trials that studied the effects of Vitrakvi (larotrectinib) and Rozlytrek (entrectinib) in tumors with a genetic alteration called an NTRK fusion led to tumor-agnostic FDA approvals for these drugs.

Research has also found that tumors with RET fusions tend to respond to RET inhibitors regardless of the tumor type. The RET inhibitor Retevmo (selpercatinib) is approved to treat lung and thyroid cancers with this mutation. But investigators on the LIBRETTO-001 trial recently reported that 47% of patients with RET fusions across numerous cancer types responded to Retevmo.

“Basket trials enrolling patients on the basis of NTRK and RET fusions have yielded incredible results. These drugs benefit the majority of patients with the relevant biomarkers,” says Schram, who has been an investigator on trials of those drugs.

The massive NCI-MATCH trial’s 39 treatment groups, enrolling at nearly 1,100 cancer centers in all 50 states, Washington, D.C., and Puerto Rico, explore the efficacy of a number of drugs to treat tumors with various genetic abnormalities. The researchers have published the findings of 19 of those groups.

Among the findings, 38% of patients with BRAFv600E mutations responded to the drug combination of the BRAF inhibitor Tafinlar (dabrafenib) and MEK inhibitor Mekinist (trametinib). In patients without colorectal cancer whose tumors had what’s called a mismatch repair deficiency, 36% responded to Opdivo, an immunotherapy drug that targets PD-1. That data helped earn the drug tumor-agnostic approval from the FDA. Just over 28% of those with AKT1 E17K mutations responded to the AKT kinase inhibitor capivasertib.

But not all gene mutations trump cancer type. Research indicates, for example, that colorectal cancers tend to be harder to attack with gene-targeted therapies, as they are sometimes better suited for other cancers such as melanoma but not for gastrointestinal cancer.

“In these cancers, if you inhibit one pathway, another pathway can sometimes compensate, leading to continued cancer growth despite inhibiting the specific gene alteration,” Schram says.

For that reason, researchers are testing drug combinations to target multiple pathways simultaneously and will continue to design both the trials that group cancers by site or tumor type and basket trials that group cancers by their genetic makeup.

Because not all tumors have a strong response to targeted drugs, the jury is still out on whether everyone with metastatic cancer of any type should get genetic analysis of their tumor. “There’s a lot of controversy,” Schram says, “about the cost-benefit ratio of doing genomic sequencing on every tumor.” Some say the tests are too expensive to justify in people who have cancers for which there are no proven-effective targeted drugs. But on the other hand, with the advent of basket trials as well as the continually dropping price of DNA sequencing, genetic analysis could open the door to experimental treatments for people who may believe they are out of options.

Increasingly, researchers are playing matchmaker between patients with metastatic cancer and targeted drugs via studies called basket trials.

Matchmakers: How Basket Trials Match Patients With Drugs Based on Their Tumors

On Halloween of 2010, David Mitchell got out of bed and immediately fell to the floor with pain so excruciating he was unable to move. A few days later, the results of his MRI showed malignant-appearing lesions up and down his spine and ribs, and he was diagnosed with multiple myeloma.

Multiple myeloma is incurable but treatable, and Mitchell had surgery to stabilize his spine and started an expensive drug therapy. For over five years, he took Revlimid (lenalidomide) manufactured by Bristol Myers Squibb (BMS). Each capsule currently sells for $833 — and cost less than $1 to make. Now he’s on a four-drug combination that costs $900,000 per year. When the three classes of recommended drugs stop working, Mitchell says some oncologists say the outlook might appear to be “dismal.”

“But I don’t look at it that way,” he says. “There are new drugs in development and coming on the market all the time. With each drug, I’m going to get enough additional time to get to the next new drug. So innovation and drug development are vitally important to me — literally life and death.”

Mitchell is not the only patient with cancer whose drugs are expensive. According to Dr. Vincent Rajkumar, hematologist and professor of medicine at Mayo Clinic in Rochester, Minnesota, every single type of cancer is expensive to treat.

“Almost every new cancer drug introduced in the last three years has been priced at more than $100,000 per year,” Rajkumar says. “The median price was approximately $150,000 in 2018.”

Medications aren’t the only cost in cancer treatment. Depending on the patient and their diagnosis, therapy can involve surgery, radiation and pharmacological therapy, as well as indirect costs like lodging, transportation, child care, lost wages, special food, fertility treatment or adoption fees. But medications are one of the biggest costs and among the fastest rising. While research and development do take a significant investment, why do they require such aggressive pricing? Or is too much money spent on marketing and advertising, or perhaps on high salaries for executives? These questions are receiving more scrutiny than ever before.

The American Cancer Society (ACS) reports that Americans with cancer paid nearly $4 billion out of pocket in 2014. Employers, insurance companies and taxpayer-funded programs paid roughly $87.8 billion that same year. For patients with multiple myeloma like Mitchell, drugs account for approximately 60% of the cost of care, according to a study published in Blood in 2019.

Rajkumar warns that programs that lower out-of-pocket costs for patients can be helpful but offer only “Band-Aid” solutions that don’t fix the larger problem.

“The reason drug prices in America are so high is because most other countries have governments that negotiate directly with drug companies,” Mitchell says.

“And we have laws and policies in the United States that literally prohibit the government from using its purchasing power through Medicare (the largest payer of medications) to lower drug prices. Consequently, we have a system in which the drug companies have all of the pricing power, and we have none of the purchasing power.”

Mitchell, who is the CEO and founder of Patients for Affordable Drugs, points out that the U.S. government negotiates prices for nearly everything from aircraft carriers to copy paper. Why not for the cost of lifesaving drugs for millions of Americans?

Because of the Medicare Modernization Act. Passed in 2003, this act includes a noninterference clause that states that the secretary of health and human services cannot intervene in negotiations between drug companies and insurance companies’ pharmacy benefit managers. According to Mitchell, Billy Tauzin, who represented Louisiana then as a Republican in the U.S. House of Representatives, and was a primary advocate for the bill, became CEO of a trade association for the pharmaceutical industry earning an annual salary of $2 million in January 2005.

“Basically, Medicare needs to buy the drug for all beneficiaries who need it and pay whatever price pharmaceutical companies set,” Rajkumar says. “That’s the recipe for the problem we have right now.”

For many new drugs, there are no alternatives. These monopolies should be temporary and only until generic competition enters the market when patents expire. However, this often does not happen because by the time the patent ends the drug has already been replaced by a “new and improved” version with a new patent that is now the standard of care.

Stacie Dusetzina, associate professor of health policy and Ingram Associate Professor of Cancer Research at Vanderbilt Medical Center in Nashville, Tennessee, says BMS has been criticized by the Food and Drug Administration (FDA) for withholding samples of Revlimid from generic manufacturers.

“This makes it hard for companies to do the tests they need to do to get a generic on the market,” Dusetzina says. “Other companies do things like create slightly different formulations or use something like an auto-injector or device that can be patented. There’s a whole bag of tricks.”

Even when generics are available, Dusetzina says, people on Medicare can have higher out-of-pocket costs for generics than for brand names because of a loophole in the Medicare Part D benefit.

“This monopoly is completely a function of our laws and the policies that have been purchased with billions of dollars in lobbying and campaign contributions by the drug companies through the years,” Mitchell says.

Rajkumar agrees and noted that pharmaceutical companies and their trade organizations spent $220 million on lobbying in the U.S. in 2018.

Patients’ lives are dependent on new innovation of these drugs. Maybe the high costs are necessary to drive development. It takes about 12 years for a drug to go from testing to approval, and only about 10% to 20% ever reach the market.

But this still doesn’t explain why Americans pay at least twice as much for medications as patients do in other countries.

Newer cancer therapies easily cost upward of $100,000. Why so much? Who sets the prices and what can patients do if they can't afford them?

CURE^® Summer 2021 Issue

Treating Cancer as Patients Age

Peer Support Helps Patients Navigate Their Cancer Journey

Aiming for New Targets: Emerging Therapies in Melanoma

Pet Companionship During the Cancer Journey

Recognizing Cancer Fate Without Losing Control

‘No One-Size-Fits-All’ First-Line Treatment for Mantle Cell Lymphoma

Matchmakers: How Basket Trials Match Patients With Drugs Based on Their Tumors

Too Much Money for the Medicine

Latest News

CURE® Summer 2021 Issue

Treating Cancer as Patients Age

Peer Support Helps Patients Navigate Their Cancer Journey

Aiming for New Targets: Emerging Therapies in Melanoma

Pet Companionship During the Cancer Journey

Recognizing Cancer Fate Without Losing Control

‘No One-Size-Fits-All’ First-Line Treatment for Mantle Cell Lymphoma

Matchmakers: How Basket Trials Match Patients With Drugs Based on Their Tumors

Too Much Money for the Medicine

Latest News

CURE^® Summer 2021 Issue