Checkpoint Inhibitors Show Promise in Lung Cancer
- Imfinzi (generic name: durvalumab), an immune checkpoint inhibitor, works by helping the immune system recognize and attack cancer cells — and has shown real promise in treating a specific type of small cell lung cancer (SCLC).
- New research, presented at this year’s American Society of Clinical Oncology (ASCO) meeting showed Imfinzi could reduce the risk of death for patients with limited-stage small cell lung cancer (LS-SCLC) by 27%.
- This study supports Imfinzi as the new standard of care for LS-SCLC post-chemoradiotherapy.
- The research is especially promising as much of the progress in the lung cancer field has been in treating non-small cell lung cancer — as it’s significantly more common than small cell lung cancer.
While much of the progress in the field has been in treating the more common non-small cell lung cancer (NSCLC), new research is showing the promise of Imfinzi in treating significantly less common small cell lung cancer (SCLC).
Read MoreA New Standard for SCLC
“SCLC is one of the most aggressive types of lung cancer. The ADRIATIC trial is a landmark study and provides a new standard of care with the addition of immunotherapy for patients with early-stage SCLC who are being treated with a goal of curing their cancer,” said Dr. Lauren Byers, thoracic section chief in the Department of Thoracic-Head & Neck Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston.Dr. Byers pointed out that using Imfinzi helped patients live for years compared to many other treatment approaches where the benefits were measured in months. This is a big deal for patients.
“It’s also an important study because of the magnitude of benefit that patients received with the addition of durvalumab consolidation, with an average improvement in OS (overall survival) around 2 years,” she said.
“This is in contrast to many clinical trials in SCLC, where often, the benefit may only be measured in months. Similar to other lung cancers, and you’ve heard about many advances related to personalization of lung cancer treatment for patients, we now know that SCLCs are really different types of lung cancers.
“…I think one important next step will be to understand who’s benefiting the most with the addition of durvalumab and how can we start thinking about personalizing treatment for the different subtypes of SCLC to further build on this and continue to make progress for these patients.”
What Did the Research Show?
The ADRIATIC trial is a randomized phase III clinical trial. A phase III clinical trial tests the effectiveness and safety of a new treatment on a large group of people to confirm its benefits and monitor side effects. This type of trial is considered a high evidence study.
It enrolled a total of 730 patients with stage I to III LS-SCLC who completed four cycles of concurrent thoracic radiation therapy (CRT) within 1 to 42 days.
Patients were randomized in a ratio 1:1:1 to receive Imfinzi alone, or in the other group, Imfinzi alongside tremelimumab (a type of drug known as a monoclonal antibody) for up to four doses, followed by Imfinzi up to 24 months.
- Progression-free survival (PFS) was significantly prolonged in the group that received Imfinzi (16.8 months vs. 9.2 months).
- Overall survival (OS) was also better in the Imfinzi group (55.9 months vs. 33.4 months).
The rate of severe side effects was the same in both groups: 24%.
About 16% of the participants in the Imfinzi group stopped treatment because of side effects compared to 11% in the placebo group. About 38% of participants in the Imfinzi group developed pneumonitis (inflammation of the lung tissue) compared to 30% in the placebo group.
Understanding Overall Survival (OS) and Progression-Free Survival (PFS)
When doctors talk about cancer treatments and how well they work, they often use two important terms: overall survival and progression-free survival. These terms help us understand the effectiveness of a treatment. In the ADRIATIC trial, Imfinzi improved both progression-free survival and overall survival.
Overall Survival
Overall survival (OS) is the length of time from either the diagnosis or the start of treatment that patients are still alive. It doesn’t matter if the cancer has gotten worse or if there are other health issues — what matters is that the patient is still living.
For example: Imagine a group of 100 people who start a new cancer treatment at the same time. If 70 of those people are still alive five years later, the overall survival rate at five years is 70%.
Progression-Free Survival
Progression-free survival (PFS) measures the length of time during and after treatment that the cancer does not get worse. “Progression” means that the cancer has grown, spread, or worsened. PFS is the time patients live without the cancer growing or spreading.
Example: Consider the same group of 100 people. If 50 of them have their cancer stay the same without getting worse for three years after starting treatment, the progression-free survival rate at three years is 50%.
Why These Terms Matter
Overall Survival: This is important because it tells us the total life expectancy of patients after treatment.
Progression-Free Survival: This is useful to know how long a treatment can keep the cancer from getting worse.
Sometimes, a treatment might not extend overall survival much, but it can significantly improve PFS, meaning patients have more time without their cancer growing.
What is Immunotherapy?
Imfinzi is a type of immunotherapy, a type of cancer therapy that harnesses a patients immune system to recognize and fight cancer.
The immune system uses its white blood cells to attack cells in the body that are abnormal or foreign. Cancerous cells have the ability to prevent the immune system from doing its job. The cancer produces certain proteins to protect the tumor from white blood cells. As a result, the body does not recognize the tumor as abnormal.
Immunotherapy drugs stop this from happening and ensure the white blood cells recognize the cancer cell properly and attack it. The cancer cells themselves are not necessarily difficult to fight. However, they continue to divide rapidly. So, immunotherapy drugs help a patient’s immune system control their cancer on its own before it can spread.
Checkpoint Inhibitors: How Do They Work?
Imfinzi is known as a checkpoint inhibitor. Our immune cells have proteins on their surfaces that interact with proteins in normal, healthy cells. These proteins have the ability to either start or stop an immune response, earning the name ‘checkpoint proteins.’ Cancer cells will mimic these checkpoint proteins to protect themselves from being attacked by immune cells. Checkpoint inhibitors target these proteins in cancer and immune cells.
- Checkpoints are proteins on T cells, which is a type of immune cell. T cells attack harmful substances such as bacteria, viruses, and even cancer cells. PD-1 is an example of a checkpoint found on this type of immune cell.
- Lung cancer cells come equipped with their own protein, known as PD-L1. It tells the T cell, “Ignore me, I’m not doing anything wrong.” It’s kind of a cloak that lets it hide from the immune system.
- The PD-1 to PD-L1 interaction turns the immune system “off,” allowing cancer cells to hide. When interaction is blocked by either PD-1 or PD-L1 inhibitors, suddenly the negative switch is turned off and the immune system can begin destroying and ultimately killing cancer cells.
What are the Side Effects?
The risk of side effects, in some aspects, is inevitable with any medical treatment or procedure. Once your immune system starts working at full throttle, it may lead to some serious side effects. It can attack other organs, including the liver, lungs, intestine, and hormone-producing glands. If this occurs, it is important to consult with your healthcare team, and it may warrant ceasing treatment for some time.
Many oncologists take patients off their immunotherapy medication because of side effects. In some instances high dose steroids may be used to improve side effects. Unfortunately, several of the side effects from immunotherapy are irreversible and patients will live with them for long periods of time.
The most common side effects are:
- Rash
- Diarrhea
- Fatigue
- Itchiness
- Muscle or bone pain
- Stomach pain
- Lung inflammation such as pneumonitis
Though rare, more serious side effects include:
- An overactive immune system
- Allergic reactions
- Kidney problems
- Nerve damage
Promptly report any unusual symptoms to your doctor.
Questions to Ask Your Doctor
- Am I eligible to begin treatment with Imfinzi?
- Will insurance cover this treatment for my disease?
- What sort of side effects should I be aware of?
- If side effects don’t improve, how can we manage them?
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