First ever FDA-approval of immunotherapy plus chemotherapy combination for advanced mesothelioma
Today, the U.S. Food and Drug Administration (FDA) approved the third ever treatment for mesothelioma. As of today, in addition to the standard chemotherapy regimen and the immunotherapy regimen, the combination of immunotherapy plus standard chemotherapy is available to clinicians for the treatment of patients with advanced or metastatic mesothelioma in a first line setting.
Keytruda, which is the industry name for Merck’s pembrolizumab agent was approved after a positive 2023 Italian/Canadian collaborative study demonstrating a survival improvement for their immuno-chemotherapy combination.
About the clinical trial
The IND.227 clinical trial had enrolled 440 treatment-naive patients randomizing them into two groups, one of which was experimental. The first group received only standard chemotherapy, while the second group received chemotherapy plus Keytruda (pembrolizumab). The experimental arm saw a one month survival improvement (17.3 months’ survival as opposed to 16.1 months for the chemotherapy alone arm). However, as is the case with other immunotherapy data in mesothelioma, patients with the more aggressive types of mesothelioma (biphasic and sarcomatoid) gained the most from the immunotherapy addition. For this group, the survival benefit exceeded 4 months over the survival of their peers in the non-experimental treatment arm, an improvement which ultimately also led to this approval.
About pembrolizumab (Keytruda)
Pembrolizumab is an immunotherapy agent known as a checkpoint inhibitor. Checkpoints are proteins located on t-cells that, when bound together with partner proteins on the tumor cell, disable the immune response of the t-cell against the tumor cell. It functions sort of like a handshake. Disrupting this process, or inhibiting this connection, allows the t-cells to recognize the tumor as a foreign entity and kill it. The class of drugs called checkpoint inhibitors bind to these checkpoint proteins (known as PD-1 and PDL-1, depending on their location) so that no handshake can occur, thus effectively taking the breaks off the immune system.
About mesothelioma treatment
Mesothelioma treatment has lagged behind other cancers. Its first FDA-approval came in 2004 when Alimta plus cisplatin chemotherapy extended median survival by 3 months (from 9 months to 12 months). For over 16 years, mesothelioma didn’t see any new treatments added to its line-up until 2020 when a landmark study of two immunotherapy agents, nivolumab and ipilimumab (Opdivo/Yervoy) by Bristol Myers Squibb, demonstrated a significant improvement in overall survival of over 4 months (from 14.1 months to 18.1 months), leading to its approval shortly thereafter. This third approval is a therefore a welcome addition to the treatment arsenal for mesothelioma.
Mesothelioma Centers of Excellence Provide Opportunities to Improve Wellness
We constantly are telling people to go to a Center of Excellence if you have been diagnosed with malignant mesothelioma. There are obvious reasons for why we advise this. They offer cutting edge treatment, experience, wealth of knowledge, clinical trials, and are staffed by a group of professionals who constantly are trying to push the envelope for more.
We usually do not talk about the other opportunities at these sites. It is a check on the person’s individual wellness. One of the definitions of wellness is “the act of practicing healthy habits on a daily basis to attain better physical and mental health.” When people travel to these centers one of the benefits they receive is a checkup on what the disease has done to their overall “wellness” and a chance to fight malignant mesothelioma on a daily basis. We are very honest in telling you that there is no cure, but we are learning every day how to live well with this disease. As always, each journey is different and some have it easier than others.
Opportunities for wellness are provided in the following ways at a Center of Excellence:
- Hope, which is a feeling of expectation and desire for a certain thing to happen. Patients come in search of extending their lives. Patients travel from near and far because they are searching for better, they believe they are giving themselves the opportunity to put themselves in a better position to deal with this aggressive cancer.
- Community is available at these centers. When one person in the family is diagnosed everyone is affected. Patients need support. Family members need support.
- Spiritual needs are met at most centers. As we have learned through the years, we know the physical aspect is only one part of this disease. We meet people on the platform they are at and we provide what they need. Some people are in search of spiritual guidance, a listening ear, or just a friend.
- Nutrition is also another component of wellness. We encourage people to eat according to what their bodies need. We have a host of professionals who can help improve someone’s nutritional status. Hints and suggestions about what foods have worked for other patients can be very helpful.
- Education – from the moment you are introduced to the center we start with the basis of this disease. It is broken down into simplest forms and we start to paint the picture of what mesothelioma has done to you and what a Center of Excellence can do for you.
We all know that these are different times but we urge you to give yourself the best chance at getting the best care. Above are some of the attributes that are part of a Center of Excellence. Please consider giving yourself the best chance for treatment. Choose specialized personal care for a rare disease with medical experts who are invested in your state of wellness.
FDA Approves Opdivo and Yervoy as First New Treatment for Mesothelioma in 16 Years
by Eleanor Ericson, RN
The Food and Drug Administration has approved a new treatment for the rare disease malignant pleural mesothelioma. The new treatment is two immunotherapy drugs working together as first line therapy to treat patients that are not surgical candidates. This is the first new drug therapy approved by the FDA since 2004 when Cisplatin and Pemetrexed were approved as chemotherapy options for patients with mesothelioma.
The two drugs are Opdivo (Nivolumab) and Yervoy (Ipilimumab). The phase three clinical trial that was conducted internationally used these two immunotherapy drugs that work as checkpoint inhibitors. Together, they work on the T-cells to identify the tumor cells and target them. T-cells are part of the immune system; they are specific white blood cells. The T-cells’ role is to circulate looking for foreign substances. Opdivo helps the T-cells discover the tumor cells, and then Yervoy activates and proliferates the T-cells to destroy the tumor.
In the clinical trial named CheckMate 743 which began recruiting in 2015, Opdivo 360mg was administered by IV every three weeks. Yervoy, 1mg/kg IV was administered every 6 weeks. They were administered together for up to six cycles or to disease progression, unacceptable toxicity, or completion of two years of therapy.
There are side effects to this therapy. The most common ones are fatigue, musculoskeletal pain, rashes, diarrhea, dyspnea, and nausea. These drugs can also cause immune mediated pneumonitis, colitis, and hepatitis. These reactions can be serious and life threatening.
This combination of drugs has proven to extend overall survival of patients that are diagnosed with malignant pleural mesothelioma that are not candidates for surgery. Of the nearly 3,000 patients diagnosed a year in the United States, approximately 20 to 30 percent are deemed surgical candidates. Up to this point the non-surgical patients were offered standard chemotherapy using Cisplatin and Pemextred with limited success.
There are three main cell types of malignant pleural mesothelioma. Epithelioid is the major type making up around 60 to 80 percent, sarcomatoid is less than 10 percent, and mixed or biphasic around 10 to 15 percent. The most resistant to treatment has been sarcomatoid and mixed cell types.
This new therapy is particularly encouraging for patients with sarcomatoid and mixed cell type. The two year survival of patients with this new therapy was 38 percent compared to 8 percent after two years with standard chemotherapy. The median survival was 18.1 months as compared with the current median survival of 8.8 months.
This is encouraging news and hopefully the beginning of more approvals and longer survival leading to a cure!
Two Years Later: Remembering Dr. David Sugarbaker
by Eleanor Ericson, RN and Lisa Hyde-Barrett, RN
In life there are many people that you come in contact with and a few that leave a lasting impression on you. Whether personally or professionally, these influencers can guide your life’s journey in ways that you never planned. Wherever you encounter them – in your youth or adulthood – they can become people whose qualities and approach to life you admire and want to emulate.
It has been two years since one of the pioneers in the treatment of malignant mesothelioma left this world. We would like to reflect upon what Dr. David Sugarbaker has taught us. He was known throughout the world as a world class thoracic surgeon, a teacher, and a man who was willing to push the envelope for greatness and a true leader. As nurses we were fortunate to know and work alongside him. As professionals his teachings were limitless. We would like to share a few things this man has taught us.
He taught us to listen to patients, despite what numbers and physical appearance might show, not ignoring the patient’s feelings and thoughts. Patient’s sometimes feel as if something is not right, and these intuitions cannot be ignored.
Hope was always in the equation. He knew that patients facing a rare disease need to have this in order to move forward. The odds can be stacked against you, but he encouraged all to keep an open mind. Every Tuesday during his new patient orientation he spoke about patients’ feelings – how these feelings should not go unacknowledged, and how they should be shared with support teams. He also shared that this is a family illness and we all need to take care of each other. We are sure these thoughts about family illness was where support teams were born.
Dr. Sugarbaker also knew how to treat each patient individually. He taught us that although the disease has symptoms that are similar, each patient’s disease is unique like someone’s own fingerprints. We were encouraged to find out about each patient, we asked questions about what brought them to seek medical attention, where are they from, what were their risks. All of this information became fascinating to us. We became passionate about these patients, and our business of the first aftercare for mesothelioma patients was initiated.
Overall the most important lesson to us of Dr. Sugarbaker’s legacy was to try to provide excellent care to these patients, and advocate for the patient and families when they were unsure of what direction to go. Dr. Sugarbaker is remembered by hundreds of doctors that he trained and inspired, as well as the thousands of patients and families that he touched. Today many professionals who care for mesothelioma patients have taken these lessons and incorporated them in their practice.
To have made a difference is what we all strive for in our lives. Dr. David Sugarbaker made a difference.
Like Mesothelioma, There Is No Magic Bullet for COVID-19
The dream of curing any disease has always been a magic bullet. Take one of these and you will be cured. We are used to things being done instantly. Unfortunately, dreams don’t always come true. Diseases are more complex than that. Science has a process and it takes time.
COVID-19 is no exception. Before the hoped for vaccine is a reality there have to be some intermediate steps taken to help prevent the spread of the virus – steps we can do to protect ourselves and others.
Researchers discovered with malignant mesothelioma that a multi-disciplinary approach has been effective in advancing treatment. No magic bullet, but a combination of therapies for a specific type and stage of disease that helps a certain percentage of people. This has not been determined overnight but required a process that has involved years of scientific research resulting in small steps forward.
Until we get to the point that scientists have developed a vaccine, there are some proven ways to help contain the spread of the virus. A recent article in the New Yorker by Dr. Atul Gwande summarizes the approach that has been used successfully at the Mass General Brigham in Boston. This approach works when people follow all of the parts of the process by working together. Their four points include:
- Hygiene measures. Infectious disease experts have long said the single most important thing you can do to stop the spread of disease is washing your hands. The usual recommendation is 20 seconds with hot soapy water, or with anti-bacterial hand sanitizer. It is recommended that you wash your hands before eating, after touching your face or nose, sneezing, coughing, or touching a potentially contaminated surface.
- Screening for symptoms of the virus. Before going out people have been asked do they have a fever? Do they have a cough? Have they been in contact with any one who has tested positive for COVID-19?
- Social distancing. The virus is spread from person to person, between people in close contact with one another within about 6 feet. It also transfers via respiratory droplets when an infected person coughs or sneezes. Wearing masks when we are out of the house to protect ourselves and others can be a huge help.
- Culture change. The COVID-19 virus has changed our way of life. Things we did before are not recommended now or even available. Protecting ourselves and our neighbors from spreading the disease is becoming all of our responsibilities. For these steps to be successful we need to all participate to the best of our abilities.
None of these alone will stop the spread of the virus. None of these measures are the “magic bullet.” The four measures taken together will reduce the spread of the virus until a vaccine is developed. While none of these steps are harmful physically, they do take some effort and follow through. As a result they can help slow the virus and can help the vast majority of us psychologically with some peace of mind.
Stay safe!
Tips for Mesothelioma Patient Routines During COVID-19
The COVID-19 virus has changed our everyday routines. Despite your challenges or adversities, life is very different. Being diagnosed with a rare disease is overwhelming and that alone changes lives dramatically. People that are newly diagnosed with malignant mesothelioma are waiting to come to a Center of Excellence. While waiting for future appointments or treatments how does one not become overwhelmed?
The definition of a routine is a sequence of actions regularly followed: a fixed program. Our daily lives are for most a routine, but when we are thrown a curveball like a pandemic or a rare diagnosis it can upend any semblance of normalcy. Many believe that routines prime you for success. They can prevent you from stumbling through the day, and allow us to get important things done. High achievers tend to find routines that work for them and adhere to them which they credit for their success.
Incorporating your routine and having a new diagnosis of mesothelioma can be difficult. Physically this can be challenging. If you are a walker and now you are experiencing shortness of breath this may inhibit your daily walk or exercise. With the right adjustments, you can continue with your exercise regime at some level so that you can continue to stimulate those endorphins that make us feel good. Numerous studies have shown that exercise is the key in fighting depression and anxiety.
This is one example of how routine can help you get through the day. One other idea about routine is about reflection of what you did for the day. At the end of the day celebrate every little success. If you were able to walk the same distance as you did yesterday or go longer, celebrate. You are worth it. If you write down your goals for the day, review the end of the day success. It is in black and white and there is no denying it. If you choose not to jot down goals, you can use a smartphone to track your progress. There are many apps for exercise, nutrition , and meditation that are free.
The world is changing and we all need to adapt. We need to make the most of our days and be accountable for our success. Reach out to someone and have them help you with your new routine. There are many people who can help with the new normal. According to Aristotle “ We are what we repeatedly do. Excellence, then is not an act, but a habit.
Clinical Trials: What Are They and How Can They Advance Treatment
COVID-19 has impacted our daily lives throughout the U.S. This previously unknown virus that has caused the pandemic we are currently in has scientists all over the world researching for a cure.
The virus is educating a lot of people about the clinical trial process. As scientists race to find a cure for this deadly virus, the process that is in place for approval for new medications, treatments, and vaccinations is being questioned. Why does it take so long? Why is participation so low?
Patients, family members, and experts who are dealing with malignant mesothelioma know that the process to improve therapy leading to a cure is slow. There are requirements as the process is rigorous with defined stages, criteria, and approvals.
One of the challenges of conducting a clinical trial is to get participation in the trial. All participation is voluntary and can be withdrawn at any time. It is estimated that less than 5 percent of all adult patients diagnosed with cancer participate in clinical trials. Some of the reasons people give for not participating are:
- Lack of awareness, patients didn’t know about it.
- They don’t think they qualify.
- Fear and safety involved.
- The inconvenience of location or added responsibilities.
- Confusion over whether it is covered by insurance.
It is reported that 25 percent of cancer trials failed to enroll a sufficient number of patients, and 18 percent of trials closed with less than half the targeted enrollment.
Research from 2019 gives another perspective. The article published in the Journal of the National Cancer Institute in March of 2019 written by Unger JM, Validya R, Hershman DL, et al did a systematic review and analysis of the structural, clinical, and physician and patient barriers to cancer clinical trial participation. Their findings in a study funded by the National Cancer Institute included that:
- 55.6 percent of patients did not participate in a trial because no trial was available for their type or stage of cancer at their treatment center.
- 21.5 percent of patients were ineligible due to criteria that did not include them such as co-morbidities.
- 22.9 percent of patients had physician and patient related barriers, such as not being asked to participate or refusing by the patient.
As we continue to live through this pandemic and people are becoming more aware of the clinical trial process, there are reports of up to 16,000 people – mostly young – that have offered to participate in the development of a vaccine. They are volunteering to be given the vaccine and then exposed to the coronavirus as part of a study to evaluate a vaccine that is still in the experimental phase.
COVID-19 has changed our lives. Hopefully a new awareness of the opportunity to participate in clinical trials for all diseases will be one of the positive results that comes from the pandemic.
Evidence-based reasons to be seen at a Mesothelioma Center of Excellence
We have always recommended that patients diagnosed or suspected to have malignant mesothelioma be seen at a dedicated Mesothelioma Center of Excellence for diagnosis and treatment by an experienced medical team.
The pandemic we are currently in has made it difficult and sometimes impossible to do this. As people all over the country follow distancing guidelines, we are realizing in our own worlds that we cannot be teachers, hairdressers, cook like chefs, do DYI projects like on TV, and we cannot treat ourselves for medical issues.
One of the perspectives we are gaining out of this pandemic is the one to respect experience. There are skill sets involved in being an expert. With experience comes relationships – respect what experience can bring to your situation.
The pandemic has allowed us to re-examine our relationships with each other and what is important to us. Caring for patients with malignant mesothelioma is complex. Everyone is different and their expectations are different.
When we slowly get back to our lives before the pandemic and start looking to our experts for care, what should that care look like?
In 2017, The John A. Hartford Foundation and the Institute of Healthcare Improvement along with the American Hospital Association and the Catholic Health Association of the United States came up with the “4Ms.” These are four evidence-based elements of high-quality care. The guidelines are aimed at treatment of the older adult, but really apply to all.
- What Matters – what are the persons goals, what do they want?
- Medication – what medications are necessary? How do these medications affect the person’s mobility or cognition? Is that what they want?
- Mentation – is the person depressed? Are they suffering from delirium? Has their dementia been identified?
- Mobility – is the person safely able to move around? Are they falling? Are they safe?
In the Mesothelioma Center that we are very familiar with, these are standards of care. When you come to a Mesothelioma Center of Excellence you will be treated by experienced professionals that have incorporated these evidence-based practices into your care – before and after the pandemic.
How Mesothelioma Patients Can Take Care of Themselves During COVID-19
As we continue social distancing, washing our hands, and staying in our homes, a new normal is settling in. For people that are dealing with malignant mesothelioma as well as the COVID- 19 virus, day to day living can be extremely stressful during these uncharted times. What can people who have malignant mesothelioma do day to day?
- Back to basics like eating right, high protein diet.
- Walking daily outside if able.
- Limiting your alcohol intake.
- Taking your medications as prescribed.
- Keeping your spirits up.
- Having a routine that includes adequate sleep.
- Limit your time watching the news and social media.
At times, fear creeps in for all of us. We fear what is going on around us, what is coming, when it will all end and when our “normal” lives come back. For those dealing with malignant mesothelioma either as a new diagnosis or have been living with the diagnosis, this is a particularly challenging time. An article in Psychology Today by Laura Markham PHD, “Coping with Fear in the Face of a Pandemic,” has suggestions for when worry and fear take hold of us.
- Use your pause button – stop and take several deep breaths to calm your body down.
- Notice what you are worried about – if it is something in the future, it might not happen and you cannot control it anyway.
- Calm your mind by taking charge of your thoughts – you can handle it.
- Empower yourself and your family – cultivate positivity.
- Consciously choose love instead of fear.
If you are under treatment for malignant mesothelioma there could be some specific questions requiring answers. Although the focus is on taking care of coronavirus patients in most hospitals and Centers of Excellence, the mesothelioma team is still available.
Call your team. If you don’t have a dedicated mesothelioma team, reach out – the experts are available. Remember you are not alone even when it feels that way.
Balancing Mesothelioma with the Coronavirus Pandemic
When someone is diagnosed with malignant mesothelioma, the battle is both mental and physical. The symptoms are numerous and some more frightening than others. Mentally it can have an outsized effect on one’s peace of mind, affecting your physical wellbeing as well as your emotional wellbeing.
So how does a mesothelioma patient keep mind and body in sync during a strenuous time like the coronavirus pandemic?
First, look around at yourself and jot down your physical symptoms. Put factual numbers to paper. A few strategies you might consider include:
- Monitor daily weight.
- Monitor calorie intake if you can, or just list what you eat.
- If you have an O2 sat monitor use that and record the findings.
- If you don’t have an O2 sat monitor monitor, record the distance you can walk each day.
Now that really is the easier part. Mental wellbeing can be a challenge. How do you keep your head in check and not get carried away to dark thoughts and fear? If you are having a hard time being calm, there is a fair amount of advice available. Here are some different approaches:
- Close your eyes, take a deep breath, and exhale slowly.
- Say out loud three things you are grateful for today.
- Connect with others. Talk with people you trust about your concerns and how you are feeling.
- Take a break from news, including social media.
If these ideas aren’t working, contact your primary care provider and they will try to help with your physical or mental challenges at this time. Reach out to your mesothelioma team. Remember that mesothelioma patients are high risk when it comes to COVID-19 and the virus’ related respiratory symptoms.
You are not alone. These times are uncharted territory for all of us. We can get through it with help from one another.