AstraZeneca Hopes To Advance Oncology RWE
By Ed Miseta, Chief Editor, Clinical Leader
Carlos Doti began his career in hematology more than 20 years ago, and he has seen a lot of change occur during that time. He notes 30 years ago all oncology patients were treated with chemotherapy. The industry changed in the 1990s when targeted therapies and new developments such as monoclonal antibodies appeared. Today, those advancements have increased survival rates while also producing a better quality of life for patients. In the area of chronic lymphocytic leukemia (CLL), a disease Doti is focused on as the VP and global medical franchise head of Hematology at AstraZeneca, survival rates are getting close to what they are for the general population. A major focus right now is on patient quality of life.
AstraZeneca is an emerging leader in the CLL space. It now hopes to develop treatments so patients can avoid chemotherapy, with the hope those therapies will prolong survival in patients while also producing a better quality of life.
Doti believes if a company wants to be big in oncology, it must also be big in hematology. There is a plethora of different cancers with unmet needs that he thinks AstraZeneca’s science can help. There are over 150 types of blood cancers and related disorders that impact 3.6 million people worldwide. Doti thinks the approach to treating these cancers needs to change.
There are therapies that have been produced for oncology patients which have a short treatment duration but come with difficult side effects. New targeted therapies are administered to patients for a longer duration, and this has driven the efforts to create treatments with fewer side effects. Doti notes his company does not want patients on a treatment that is effective against their disease but produces side effects that are as painful and uncomfortable as the disease. That efficacy and a better quality of life are now the dual goals of AstraZeneca’s oncology efforts.
Understand The Patient Experience
One of the first steps AstraZeneca took was to acquire a company that allowed it to bring the drug Calquence into the company. Calquence is a targeted therapy that is used to treat patients with CLL, mantle cell lymphoma (MCL), and small lymphocytic lymphoma (SLL). Prior to Calquence, some treatments had been improving survival rates of patients but not doing much to improve or maintain their quality of life.
When it comes to hematology, Doti is a caregiver as well as a physician. His mother struggled with CLL and received treatments for it. One thing she always dreaded was not the impact of the cancer or the drugs, but how her quality of life would be impacted during the treatment process. Many CLL patients can be on a treatment for years rather than months, and a challenge for those patients is continuing to live their lives as normal as possible.
“Calquence is attempting to bring the best results along with the best quality of life for all patients,” states Doti. “This is our first attempt at helping those with CLL and thus far we have treated many patients. We have identified several areas of unmet needs, including high-grade lymphomas, acute leukemias, and multiple myeloma that we think our science will soon be able to help.”
The longer time that patients will be on an oncology medication has created a challenge for sponsor companies. New, targeted therapies are extending the lives of patients and turning diseases like leukemia into a chronic condition that someone might live with for years. As patients receive treatments for five or seven years, quality of life becomes a greater concern. This is forcing researchers to pool results over several years to understand the side effects being faced by patients. Safety and efficacy are still primary concerns but combining those factors with a better quality of life is now the goal. This is forcing companies to spend more time talking to patients and advocacy groups to understand the needs of study participants.
“For example, patients will tell us how long they can sit in a clinic,” says Kelly Page, VP, global commercial head of Hematology at AstraZeneca. “They will tell you how often they can travel to the clinic, how much time they can spend away from work and family, and how much transportation they will require from caregivers. Listening to and understanding those needs is important to minimizing the number of patients who drop out of a clinical trial. If we can understand that patient experience and work to improve it, we can meet their needs and run the best study possible. However, gathering the data we need is going to take many years.”
Long-Term Data And Real-World Evidence
Once a trial is complete and a drug has received regulatory approval, the data generated during the trial needs to be supplemented with real-world evidence (RWE). Doti states clinical trials are designed for a specific population to introduce the least amount of bias possible into the results. Unfortunately, real life tends to differ from clinical trials.
A clinical trial might evaluate a treatment on 100 or 500 patients. There are over 7 billion people in the real world. Drug companies need to understand how a medication will impact a disease, how it will interact with other medications, and how it will impact a patient’s quality of life.
“That is why it is so important to continue seeking results in the real-world setting,” says Doti. “In the real world, there are special populations that may not have been included in the trial. For example, older patients or those with comorbidities may not have been recruited. Countries around the world will tend to have different standards of care and different comorbidities. Patients may be using other medications that we need to monitor. We need as wide a view as possible and not be limited to a small study population. We need to expand the patient population to include individuals of a different age, ethnicity, and geography. The clinical trial will get you the approval, but after that there is a continuous journey where researchers seek more information and ensure the proper drug is provided to the proper patient.”
“The long-term follow-up is what helps us understand a patient's need and their journey,” says Page. “The patient journey starts at diagnosis and can go on for many years. The more data we gather on patients, the more we understand what dosage forms and support they might need. We might start with an IV but learn that a subcutaneous or oral formulation may work better. We may discover how to manage side effects better. What we learn may also allow us to implement services like at home treatments if it is burdensome for patients to get to the clinic. The long-term follow-up will help us understand the patient's time on the therapy and how they live with the disease. Only then can we help them live the best life they can while being treated for the disease.”
Challenges For RWE
Doti believes the drug development industry is still in the infancy of developing real-world evidence. There are different initiatives underway, but issues do exist. There is inconsistency in the quality of the data collected as well as concerns over who owns the data (due to security issues around access to personal medical records.) Claims data exists, but Doti believes that source is questionable due to the limited amount of data available.
“The first hurdle will be the consistency of data across hospitals around the world,” adds Doti. “There will also be legal issues that companies need to circumvent and analysis issues once the needed data is acquired. The worst problem will be getting rid of noise in the data. You can have access to the data, but there are a lot of confounders. There is data in the charts of every patient around the world, and to analyze the data it will have to be cleaned. When there are 500 patients in a database, it is easy to clean the data and get rid of the noise. When there is a database with 100,000 patients, the process of getting rid of the noise will be a lot more difficult.”