Opdivo & Chemotherapy Before Surgery
- An immunotherapy drug, nivolumab, in combination with traditional chemotherapy can be given prior to surgery to patients with resectable, early-stage non-small cell lung cancers.
- It improved several clinical outcomes and decreased the chances of cancer returning.
- This treatment is Food and Drug Administration-approved and should be available to all qualifying patients through their oncologists and covered by insurance.
- Common side effects of this treatment include headaches, muscle and joint pain, swelling, chest pain, unexpected bleeding or bruising, numbness or tingling in the arms and legs, constipation, and weight loss, among others, including immune-realted adverse events.
- Immune-related side effects occur because nivolumab can cause the immune system to erroneously attack a patient’s own organs. This can cause severe allergic reactions, hormonal imbalances, and inflammation of the pancreas, kidneys, and lungs.
- All patients receiving nivolumab and chemotherapy require diligent monitoring by their oncologists through physical exams and regular bloodwork.
Recently unveiled three-year updates from a major clinical trial (CheckMate 816) show that the immunotherapy workhorse nivolumab (sold under the brand name Opdivo) in combination with traditional chemotherapy before surgery may significantly improve the long-term clinical outlook for patients with resectable, early-stage non-small cell lung cancers (NSCLCs) compared to those treated with surgery and chemotherapy alone without the addition of nivolumab.Read More
Oncologists, therefore, have a vested interest in reducing these recurrence rates for their patients. They may now be able to do so by giving their patients nivolumab and chemotherapy before surgery.
“The three-year follow-up data confirm the impact of these practice-changing data. Neoadjuvant therapy is here to stay!” proclaims Dr. Roy S. Herbst, deputy director and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital.
What Is Lung Cancer?
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Lung cancer is the leading cause of cancer-related deaths in the United States. It kills more people than colon, breast, and prostate cancers combined.
The American Cancer Society estimates that around 238,340 new lung cancer cases will be diagnosed in 2023. During this same year, it will claim around 127,070 lives.
The rate of new lung cancer diagnoses has been decreasing for the past few years. This can be attributed to a general decline in smoking during this time.
Advances in treatment have also decreased the number of deaths from this cancer. Despite these positive trends, lung cancer continues to be a major threat.
Men are more likely than women to develop lung cancer. Overall, one in 16 men is at risk for developing this cancer, while one in 17 women carry the same risk.
This risk can be increased or decreased based on many factors. Smoking, for example, substantially increases this risk. A lifetime of non-smoking decreases this risk.
Race and ethnicity can also significantly affect this risk, with black men more likely to develop lung cancer than white men.
Expert Lung Cancer Resources
When Is It Non-Small Cell Lung Cancer?
Lung cancer is divided into two major types: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).
NSCLC (80-85%) is far more common than SCLC (10-15%). Only a minority of NSCLC patients (20-25%) are diagnosed at an early enough stage to receive surgery.
Although surgery can be curative, around 30-55% of surgical patients will eventually have a cancer recurrence and will need additional treatments.
Now, the new treatment combination, nivolumab with chemotherapy, offers hope to decrease these numbers and improve patient outcomes.
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What Is Nivolumab?
Nivolumab recruits the patients’ own immune systems in the fight against their cancers. It disrupts the interaction between cell surface proteins, Programmed Death-1 (PD-1), Programmed Death Ligand-1 (PD-L1), and PD-L2.
These proteins can help cancer cells evade destruction by a patient’s native immune system. More specifically, PD-1 is expressed on the immune cells. It interacts with PD-L1 and PD-L2, which can be expressed by tumor cells.
This interaction shields the tumor cells from the immune system, allowing tumor growth and progression. Stopping this interaction can therefore help the immune system detect and eliminate cancer cells. Nivolumab does just that.
Nivolumab is a PD-1 antibody, which means that it binds to the PD-1 proteins and prevents them from interacting with PD-L1 and PD-L2. The tumor cells are thus unable to turn off the immune system, which in turn destroys them.
RELATED: Understanding How Immunotherapy Works
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The Efficacy Of Nivolumab And Chemotherapy
The efficacy of nivolumab/chemotherapy was demonstrated in the phase III CheckMate 816 clinical trial. A phase III trial offers the highest level of evidence for the benefit of a new treatment.
It enrolled 358 adults with early-stage NSCLC (stages IB-IIIA) with all levels of PD-L1 expression. They were randomly assigned to receive either:
- nivolumab plus chemotherapy for three three-week cycles
- chemotherapy alone for three three-week cycles before surgery
Treatment given to help shrink a tumor before the main treatment, typically surgery, is called neoadjuvant.
Surgeries were performed within six weeks of their neoadjuvant treatment. The investigators set out to measure event-free survival (EFS), which was defined as either:
- cancer progression prior to surgery
- cancer recurrence of progression after surgery
- progression of disease in patients who did not receive surgery
- patient death irrespective of the cause
They also investigated time to distant metastasis or death (TTDM), which was defined as the interval between trial enrollment and the development of metastatic (stage 4) disease or death.
The trial has reported favorable results earlier. In keeping with these positive results, the updated three-year results showed that nivolumab plus chemotherapy reduced EFS (57% for the combination treatment; 43% for chemotherapy alone) by a relative risk reduction of 32%.
TTDM was similarly improved.
For those who received the combination treatment, three-year TTDM rates were 71% vs. 50%, favoring the combination treatment group.
Another important metric in phase III trials is the overall survival (OS), which is the length of time patients are alive after their initial diagnosis.
The full extent of the data required to conclude an OS benefit was not available at the time of the three-year update. However, preliminary data suggest that OS may be improved with combination treatment as well.
Three-year OS was 78% for the combination treatment arm but only 64% for the chemotherapy alone arm. However, this was not statistically significant and furhter follow-up time is needed to determine if immunotherapy given in this way will help pateints live longer.
Whether this trend holds when definitive OS conclusions are reported in the future remains to be seen.
What Are The Risks Of This Treatment?
The risk of side effects with the nivolumab and chemotherapy combination is similar to that of chemotherapy alone.
In the trial, 36% and 11% of the patients who received the combination treatment experienced moderate or significant side effects, respectively.
And 38% and 15% of those who received chemotherapy alone experienced the same.
Nonetheless, immunotherapy does carry some unique side effects. Therefore, it requires diligent patient monitoring during treatment. Some of the more common side effects include but are not limited to:
- Muscle and joint pain
- Chest pain
- Unexpected bleeding or bruising
- Numbness or tingling in the arms and legs
- Weight loss
- Dry mouth
- High blood sugar
- A general feeling of a loss of physical well-being (malaise)
Serious side effects are rare but may occur. This happens because immunotherapy can cause the immune system to attack a patient’s own organs (autoimmune reactions). These can present as:
- Allergic reaction symptoms, such as rashes, fever hives, itchiness, swollen tongue, and tightness in the throat
- Hormonal problems caused by thyroid, pituitary gland, and adrenal glands malfunction. They can cause mood swings, behavioral changes, weight loss, decreased appetite, hair loss, headaches, changes in bowel and urinary habits, etc.
- Pancreas inflammation, which can result in severe abdominal pain, nausea, and vomiting
- Kidney issues that can cause blood in the urine or an inability to pass urine
- Lung inflammation, which can lead to breathing difficulties
WATCH: Treating Stage 1 Lung Cancer
Is This Treatment Available for Patients?
RELATED: New Hope For Lung Cancer Patients: FDA Approval of Immunotherapy Drug For Use With Chemotherapy Prior to Surgery Hailed As ‘Major Advancement’
For more than a year, nivolumab in combination with chemotherapy has been approved by the Food and Drug Administration (FDA) for use prior to surgery in lung cancer patients. Therefore, all appropriate patients can take advantage of this treatment combination through their oncologists.
Additionally, it should also be covered by most insurance providers.
“This treatment is FDA approved and the standard-of-care,” summarizes Dr. Herbst.
He continues, “However, it is not for everyone. [Patients’] tumors need to be deemed surgically resectable by surgeons. It is also not appropriate for patients with certain mutations, such as EGFR mutations. The therapy is also not without side effects, although they are very rare.”
Questions to Ask Your Doctor
- What to Ask Your Doctor?
- Am I eligible for immunotherapy before surgery?
- Am I more, or less, likely to respond to this treatment?
- 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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