New Option for Lung Cancer Treatment: Imfinzi
- Non-small cell lung cancer is the most common subtype of lung cancer.
- Imfinzi, an immune checkpoint inhibitor targeting PD-L1. It uses the body’s own immune system to fight cancer.
- A recent study demonstrated that that Imfinzi-based treatment before and after surgery significantly increased the time patients live without recurrence or progression events.
Data from a new trial provides compelling evidence that an immunotherapy drug called durvalumab (brand name Imfinzi) may improve outcomes. Researchers demonstrated that treating patients early with Imfinzi both before and after surgery delivers a significant and clinically meaningful benefit for resectable non-small cell lung cancer patients.
Read MoreWhat’s New?
Dr John V. Heymach, the chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center, presented some very interesting results at the American Association for Cancer Research (AACR) Annual Meeting 2023.The study looked at treatment-naive patients (those who have not received treatment yet) with resectable nonsmall cell lung cancer who got neoadjuvant (before surgery) durvalumab plus chemotherapy and adjuvant (after surgery) durvalumab. They had improved event-free survival and pathologic complete response compared with those who received neoadjuvant chemotherapy alone.
Complete response to treatment is the term used for the absence of all detectable cancer after your treatment is complete. It doesn’t necessarily mean that one is cured, but it is the best result that can be reported. It means the cancerous tumor is now gone and there is no evidence of disease.
Following neoadjuvant treatment, pathologic complete response was 17.2% in the treatment arm vs. 4.3% in the placebo arm.
These data correspond to a 32% lower chance of patients experiencing disease recurrence, progression events or mortality with the immunotherapy-based treatment when compared to chemotherapy alone.
Approximately four times as many patients treated with perioperative (around the time of surgery) durvalumab plus chemotherapy achieved a complete response when compared to those treated with chemotherapy alone.
These represent the first data presented on the benefits of perioperative immunotherapy for resectable NSCLC and adds to the growing evidence supporting the benefits of both neoadjuvant and adjuvant immunotherapy for these patients.
What is Immunotherapy?
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 a checkpoint inhibitor type of drug. 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 makes 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.
Lung Cancer Overview
Lung cancer is the second most common form of cancer, and the leading cause of cancer mortality in both men and women in the United States. It can be particularly tricky to treat because often, symptoms don't show up until the cancer has spread to other organs.
There are two main types of lung cancer, which doctors group together based on how they act and how they're treated:
- Non-small cell lung cancer (NSCLC) is the most common type and makes up about 85% of cases
- Small cell lung cancer (SCLC) is less common, but it tends to grow faster than NSCLC and is treated very differently
While this is a serious cancer, its outlook is improving. For one thing, fewer people are getting lung cancer because smoking rates are on the decline. Also, there have been improvements in surgical techniques and radiation delivery that have improved outcomes and decreased side effects. Finally, newer treatments like immunotherapy and targeted agents are dramatically improving the length and quality of life for people who are diagnosed with lung cancer.
AEGEAN Trial
This trial is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial. Phase III trials are the most important piece of scietific evidence.
The researchers looked into Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. The trial enrolled participants in 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia.
Overall, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery.
Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses. In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or mortality.
Key secondary endpoints were mPR, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, DFS, OS, safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol.
Immunotherapy 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 to subside the 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.
Are These Treatments Currently Available?
Imfinzi is approved for treating specific patients with biliary tract cancer, liver cancer, small cell lung cancer and NSCLC. Currently, it is used for treating patients with locally advanced, unresectable NSCLC following definitive chemoradiotherapy and for patients with metastatic NSCLC in combination with tremelimumab and platinum-based chemotherapy.
Unfortunately, it’s no yet available for use before surgery. But that might change soon given the data we discussed above.
Questions to Ask Your Doctor
- Am I eligible to receive Imfinzi?
- Should I receive it before or after surgery?
- What side effects might I expect from immunotherapy?
- What will my treatment cost? Will my treatment be covered by my medical insurance company?
- Should I get a second opinion?
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