For Early Non-Small Cell Lung Cancer, Immunotherapy Keytruda Before and After Surgery May Significantly Reduce Risk of Disease Progression, Promising Study Shows

The results of this study could help answer an important question about when immunotherapy drugs are best given during treatment for these patients.

The number of people able to benefit from immunotherapy drugs like checkpoint inhibitors (like Keytruda), which empower the body's immune system to fight off its own cancer, has been increasing at a rapid pace that some have lauded as "revolutionary" in cancer treatment.

So, if you've been diagnosed with NSCLC that can potentially be removed via surgery, there is a promising treatment option in the form of immunotherapy given both before and after your operation.

WATCH: Preparing for Lung Cancer Surgery

Keytruda is already approved to treat metastatic (stage 4) non-small cell lung cancer, and it “has been shown to improve survival time for patients in a meaningful way,” lead author Dr. Heather Wakelee, medical oncologist and thoracic specialist at Standford Medicine, told SurvivorNet.

However, she explained, “this new data shows that adding pembrolizumab to chemotherapy prior to surgery improves the outcomes from the surgery (better pathologic responses and higher likelihood of getting surgery) and that plus the addition of adjuvant pembrolizumab improves the event-free survival (chance of the cancer returning, the surgery not being possible, or death).”

“It is anticipated that this data would lead to the approval of pembrolizumab to be given with chemotherapy prior to surgery and as adjuvant therapy for patients with stage II or III NSCLC,” Dr. Wakelee added.

"We anticipate that this will be a really major addition to treatment standards for patients with early-stage lung cancer," Dr. Eliav Barr, chief medical officer at Merck Research Laboratories, told Fierce Pharma, the pharmaceutical news outlet.

This data, from the KEYNOTE-671 trial, is being presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Lung Cancer: The Basics

Lung cancer ranks as the second-most prevalent cancer and is the leading cause of cancer-related deaths among both men and women in the United States. Treating this disease can be particularly challenging since symptoms often remain undetectable until the cancer has already spread to other organs.

Doctors categorize lung cancer into two primary types based on their behavior and treatment approach:

• Non-small cell lung cancer (NSCLC): This is the more frequent type, accounting for approximately 85% of cases. NSCLC grows at a slower pace compared to other types and is treated differently.
• Small cell lung cancer (SCLC): Although less common, SCLC tends to exhibit rapid growth when compared to NSCLC. Consequently, it requires a distinct treatment approach.

Treating Early-Stage Lung Cancer

When lung cancer is diagnosed at an early stage, it indicates that the cancer is limited to a single lung and potentially the lymph nodes on the same side of the chest. However, if the cancer has spread beyond one side of the chest, complete surgical removal of the cancer is no longer possible.

And when surgery is possible and successful, there is still a possibility of lung cancer recurring. Additional treatments such as chemotherapy, radiation therapy, or a combination of both are often administered.

These treatments utilize potent medications and high doses of radiation to eliminate any remaining cancer cells that may have strayed from the original site.

WATCH: Surgical Options for Lung Cancer

Adding Immunotherapy

Immunotherapy is a drug that works to activate immune cells against cancer by harvesting the body's own ability to fight off the cells.

Keytruda is a form of immunotherapy called a checkpoint inhibitor, which works by interfering with signaling pathways between immune T cells and cancer cells, preventing cancer cells from hiding from the body's T cells.

When pembrolizumab or other similar immunotherapies are given, it is essentially taking the brakes off the immune system and allowing the body's T-cells to do what they were designed to do: fight off cancer cells.

People with early-stage lung cancer typically go straight into surgery. This new study suggests that receiving immunotherapy as a neoadjuvant (before surgery) treatment helps with the success of the surgery, helping to shrink your tumor beforehand.

This could lead to a very different outcome and quality of life for the patient.

The Research: What Is New?

The efficacy of pembrolizumab was demonstrated in the phase III KEYNOTE-671 randomized, double-blind, clinical trial. A phase III trial offers the highest level of evidence for the benefit of a new treatment.

The investigators set out to measure event-free survival (EFS). EFS is a measure of time after treatment that a group of people in a clinical trial has not had cancer come back or get worse.

A total of 797 patients were enrolled in the study. All of them had early-stage non-small cell lung cancer, meaning they had either stage 2, 3A or 3B and their tumors were eligible to be removed by surgery.

Patients were divided into two groups:

• Half of the patients received Keytruda + standard chemotherapy followed by surgery and postoperative Keytruda (adjuvant).
• The other half received placebo + standard chemotherapy followed by surgery and postoperative placebo.

At the median follow-up of 25.2 months, pembrolizumab showed a significant event-free survival benefit. EFS was improved by 42% in the group that received Keytruda.

Moreover, the group that received Keytruda had a higher pathological complete response rate (18.1% vs. 4%). Pathological complete response is the lack of all signs of cancer in tissue samples removed during surgery after treatment.

That means that cancer completely disappeared in 18% of patients who received Keytruda before surgery.

The rates of serious adverse events were comparable between the two groups (44.9% of patients in the Keytruda group vs. 37.3% in the placebo group).

Keytruda before surgery also helped surgeons during the procedure. Patients who received Keytruda + standard chemotherapy had more R0 resection when compared to patients who received only standard chemotherapy (92% vs. 84%).

R0 resection means that the surgeon was able to remove 100% of the tumor and did not leave anything behind, not even at a microscopical level.

Phase III Clinical Trial

A phase III trial compares new treatments with the best currently available treatment (the standard treatment). It aims to find out:

• Which treatment works better for a particular type of cancer
• More about the side effects
• How the treatment affects people's quality of life

Potential Side Effects Of Immunotherapy

The negative effects of immunotherapy can be quite severe, so it's important to inform your physician as soon as you experience any abnormal symptoms. Those who are taking more than one immunotherapy drug, referred to as combination therapy, are at an increased risk of experiencing side effects.

Common Immunotherapy side effects include:

• Fatigue
• Nausea or  upset stomach
• Joint pain
• Diarrhea or constipation
• Cough
• Rash
• Loss of appetite
• Changes in blood cell counts
• Fever

Questions to Ask Your Doctor

If you have early-stage NCSLC that can be removed with surgery, here are some questions you may consider asking your doctor to help understand what options may be available to you and make sense for you:

• Is therapy before and after my surgery appropriate for me?
• If so, am I a good candidate for immunotherapy, such as Keytruda?
• How long will I be on this type of therapy prior to surgery (neoadjuvant therapy)?
• What impact do you expect the treatment to have on surgery?
• How long do you expect me to be on this type of therapy after surgery (adjuvant therapy)?
• What are the most common side effects of Keytruda? Are there other risks?
• Are there ways to help manage those side effects?
• How and when will we know if Keytruda has been effective for me?

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