Clinical Trial Shows Promise For Stage III Lung Cancer Patients
- A phase III trial shows that adding nivolumab (an immunotherapy drug) to chemotherapy before surgery — and continuing it afterward — significantly improves outcomes for stage 3 non-small cell lung cancer (NSCLC) patients with N2 disease (cancer has spread to lymph nodes in the chest).
- Patients who received nivolumab had markedly better one-year event-free survival (70% vs. 45%) and higher rates of complete tumor clearance in surgical tissue (22% vs. 5.6%).
- Immunotherapy also helped shrink tumors and reduce lymph‑node involvement, often allowing for less extensive surgery, though about 1 in 4 patients in the study could not get surgery due to disease progression or declining health.
- Experts caution that while nivolumab can delay recurrence (cancer returning), it’s still unclear whether it improves long-term overall survival, underscoring the need for careful patient selection for this treatment and continued follow-up.
- Immunotherapy side effects may include fatigue, nausea, joint pain, and even changes in blood cell counts. In extreme cases, it can trigger allergic reactions or the need to discontinue therapy altogether.
The CheckMate 77T trial evaluated whether adding the immunotherapy drug nivolumab (Opdivo), which activates the immune system to attack tumors, to chemotherapy before surgery, followed by additional nivolumab after surgery, could improve results for these patients.
Read MoreParticipants were split into two groups: one received nivolumab plus chemotherapy before surgery and nivolumab afterward, while the other received chemotherapy before surgery and a placebo afterward.
Among the 461 patients enrolled, those who received nivolumab had significantly better event‑free survival, meaning they went longer without their cancer returning or worsening.
One year after treatment, event‑free survival was 70% with nivolumab compared with 45% with the placebo.
“For patients who do make it to surgery, immunotherapy helped shrink tumors and reduce lymph‑node involvement, often allowing for less extensive operations. But about one in four patients never reached surgery because their cancer progressed or their health declined during treatment,” Dr. Raja Flores, Chairman of the Department of Thoracic Surgery at Mount Sinai Health System, tells SurvivorNet.
WATCH: Is Immunotherapy Right for You?
The study also showed a higher pathologic complete response — no detectable cancer in the removed tissue — with nivolumab (22%) versus placebo (5.6%). Even patients with more extensive, multistation N2 disease benefited: their one‑year event‑free survival was 71% with nivolumab compared with 46% for those who received chemotherapy and the placebo.
Still, Dr. Flores urges caution.
“While immunotherapy delays recurrence or progression, we don’t yet know whether it helps patients live longer overall. We need more time to understand its impact on five‑year survival,” he says.
He also notes that immunotherapy did not increase the likelihood of patients missing surgery compared with chemotherapy alone — but emphasizes that its benefits apply only to those who ultimately make it to the operating room, highlighting the importance of careful patient selection and close monitoring.
Dr. Sabrai adds that more work is needed to “better understand who benefits from such strategies and whether immunotherapy should be continued in the post-surgical (adjuvant) setting in those patients who achieve a complete response versus those who do not achieve a complete response.”
Expert Resources on Immunotherapy Used During Lung Cancer Treatment
- Advanced Small Cell Lung Cancers Can Benefit from the Promising Immunotherapy Drug Keytruda Now, Too
- Combining Immunotherapy Drugs in Lung Cancer
- Guide to Late-Stage Lung Cancer Immunotherapy Options
- How Does Immunotherapy Drug Atezolizumab (Tecentriq) Treat Lung Cancer?
- How Is Treatment For Small Cell Lung Cancer Changing? The Era Of Immunotherapy
- Hugely Encouraging News About Lung Cancer — Immunotherapy Approved For Cancer That Comes Back
- Is Immunotherapy Right for My Lung Cancer?
Dr. Patrick Forde, Director of the Thoracic Cancer Clinical Research Program at Johns Hopkins’ Center for Research, explained that the standard treatment for resectable lung cancer is surgery to remove the tumor.
“Despite this, many patients experience recurrence of their lung cancer, and when this happens, it is usually incurable,” he said, noting that chemotherapy alone, given before or after surgery, improves patient survival by only 5% at five years.
What Is Nivolumab?
Nivolumab is an immunotherapy that helps the body’s own immune system recognize and attack cancer. It works by blocking a key “off switch” that tumors use to hide from immune cells.
Normally, immune cells carry a protein called programmed death-1 (PD‑1), which interacts with PD-L1 and PD-L2 proteins that can be found on cancer cells. When these proteins connect, they send a signal that tells the immune system not to attack. Tumors use this pathway to protect themselves and continue growing.
Nivolumab is a PD‑1–blocking antibody. It attaches to PD‑1 on immune cells and prevents it from binding to PD‑L1 or PD‑L2 on tumor cells. By disrupting this interaction, nivolumab removes the tumor’s protective shield, allowing the immune system to detect and destroy cancer cells more effectively.
What Are The Possible Side Effects?
The risk of side effects with the nivolumab and chemotherapy combination is similar to that of chemotherapy alone.
Side effects for nivolumab may include:
- Headaches
- Muscle and joint pain
- Swelling
- Chest pain
- Unexpected bleeding or bruising
- Numbness or tingling in the arms and legs
- Constipation
- Weight loss
- Dry mouth
- High blood sugar
- A general feeling of a loss of physical well-being (malaise)
WATCH: Advanced Lung Cancer Patients Say, ‘Immunotherapy Gave Me Back My Life’
Learning More About The Impact Of Chemotherapy & Lung Cancer Treatment
Chemotherapy is often recommended in patients with high-risk features such as tumors > 4cm or in poorly differentiated tumors. There are other factors your clinical team will also consider when deciding whether chemotherapy is right for you.
Chemotherapy alone used to be the mainstay of treatment for stage 4 lung cancer. It is often used with other treatment options, such as immunotherapy, radiation therapy, or targeted medications. Chemotherapy is important in stage 4 cancer because often, more localized treatment options, like focused radiation or surgery, are no longer possible due to the extent of the disease and how much it has spread to other parts of the body (also called metastasis).
WATCH: How targeted therapies can be used for advanced lung cancer
Systemic treatment of the body with chemotherapy is helpful to slow the progression of further growth of the primary cancer, prevent future metastasis, and relieve symptoms associated with existing tumors. However, chemotherapy works by killing all cell types, healthy or cancerous, that are multiplying quickly, so it does have significant side effects for the healthy tissue.
RELATED: Managing Chemotherapy Side Effects
Some patients may also be considered for other therapies, including the targeted agent osimertinib (brand name: Tagrisso) and the immunotherapy drug atezolizumab (brand name: Tecentriq). These drugs are very different from chemotherapy and are often much better tolerated. However, to receive these drugs, the tumor must test positive for certain biomarkers that allow these drugs to be effective.
Genetic testing helps distinguish specific biomarkers in cancerous tumors and determine effective treatments.
Lung Cancer: The Early Detection Issue
Lung cancer forms when cancer cells develop in the tissues of the lung. It is the second most common form of cancer and the leading cause of cancer deaths in both men and women in the U.S., SurvivorNet experts say. It’s “completely asymptomatic,” says thoracic surgeon-in-chief at Temple University Health System Dr. Joseph Friedberg.
“It causes no issues until it has spread somewhere. So, if it spreads to the bones, it may cause pain. If it spreads to the brain, it may cause something not subtle, like a seizure,” Dr. Friedberg adds.
WATCH: Detecting lung cancer in the absence of symptoms.
Scans such as X-rays can help doctors determine if a shadow appears, which can prompt further testing for lung cancer.
Some people with lung cancer may experience symptoms such as:
- A cough that doesn’t go away, that gets worse, or that brings up bloody phlegm
- Shortness of breath
- Fatigue
- Chest pain
- Hoarse voice
- Appetite loss
- Weight loss
If you are experiencing these kinds of symptoms consistently, contact your doctor for further tests.
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.
Stage III non-small cell lung cancer, the type tested in the CheckMate 77T trial, “is defined by the presence of metastatic disease to mediastinal (middle of the chest) or subcarinal (below the carina) lymph nodes. Stage III lung cancer has a high rate of recurrence and mortality post resection alone,” Dr. Sabari explains.
Questions To Ask Your Doctor
If you find yourself diagnosed with lung cancer and are concerned about the long-term impacts, here are some questions you can ask your doctor.
- Has my cancer spread to other parts of the body?
- Based on my cancer stage, what are my treatment options?
- What are the side effects of my recommended treatment?
- Are there any new treatments or clinical trials I should consider?
- What financial resources are available to get the treatments I need?
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