Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy
What Is Non-Small-Cell Lung Cancer?
About 80% of people who have lung cancer have non-small-cell lung cancer. NSCLC usually spreads more slowly than small-cell lung cancers.
Both cancers affect the lungs and have similar symptoms, but they're treated differently.
TypesThere are three main categories of NSCLC:
Adenocarcinoma: This is the most common type. It usually spreads more slowly than others, and it's more likely to be found earlier. It's often linked to a history of smoking, but it is also the most common type of lung cancer seen in nonsmokers.
It starts in the cells that make mucus, and it's usually found in the outer parts of your lung.
Squamous cell (epidermoid) carcinoma: This starts in the lining of the airways in the lungs. About a quarter of all lung cancers are this type. It's often linked to a history of smoking.
Large-cell (undifferentiated) carcinoma: This fast-growing cancer can be in any part of the lung. Because it spreads quickly, it can be harder to treat. About 10% of non-small-cell lung cancers are this type.
CausesMost lung cancers are linked to smoking. Many people who get lung cancer either smoke or have been around people who smoke.
Other things that make lung cancer more likely include:
You may not have any. NSCLC might be found during an X-ray or other exam you may have for something else.
If you do have symptoms, they can include:
If the cancer spreads to other parts of your body, you might have:
Your doctor will do an exam and ask you questions about your symptoms. They'll ask whether you smoke or have been around people who smoke. You might need tests to look for tumors in your lungs and to see whether the cancer has spread.
Tests might include:
Based on what your doctor finds, your cancer will be assigned a stage. It takes into account three things you may hear called TNM:
These three things are used together to determine the lung cancer stage: I, II, III, or IV. Some stages are subdivided into A and B. The lower the stage, the better your chances for recovery.
TreatmentThere are many of them for non-small-cell lung cancer. They're based on the spread of the cancer, as well as your overall health.
Surgery: If you have early-stage cancer, your doctor will probably suggest you have surgery to remove it. You could have all or part of your lung removed.
Radiation: This can kill the cancer cells left after surgery or may be the main treatment in place of surgery. Radiation can also shrink tumors before surgery so they're easier to remove. It uses high-energy rays to target cancer cells.
Radiofrequency ablation: High-energy radio waves are used to heat the tumor. Then electric current is passed through a probe to destroy your cancer cells. This is an option if you have small tumors that are near the outer edge of your lungs.
Chemotherapy: These drugs can be taken by IV or pills to help kill the cancer. You may get them before or after surgery, with radiation, or as the main treatment.
Targeted therapy: This focuses on the changes your cells go through when you get NSCLC. You'll usually get this when your cancer has spread. Sometimes you'll take these drugs along with chemotherapy.
Immunotherapy: This helps your own immune system fight your cancer. It does this by making it easier for your body to recognize and destroy cancer cells. You'll usually get this if your NSCLC is advanced, or after other treatments haven't worked.
Progress In Early-Stage Non-Small Cell Lung Cancer Treatment
The panel shares insights on the progress in early-stage non-small cell lung cancer treatment and the potential role of neoadjuvant therapy. Sponsored by Bristol Myers Squibb.
Danielle Hicks: Now I want to talk about progress in early-stage non-small cell lung cancer. There have been some developments in this space, particularly, specifically, in 2022 and 2023. Doctors Towe and Mohindra, can you please comment on what that means to somebody diagnosed with the disease today?
Dr. Nisha Mohindra: There is a lot of excitement in this space. There's been ongoing clinical research across early stages of lung cancer that bring options that can be given before surgery in that neoadjuvant setting to potentially lower the risk of recurrence for some patients. For example, in 2022, the FDA approved an immunotherapy called Opdivo®, otherwise known as nivolumab in the neoadjuvant setting.
Danielle Hicks: Can you tell me a little bit more about Opdivo?
Dr. Nisha Mohindra: Of course. Opdivo is used in combination with chemotherapy that contains platinum and another chemotherapy medicine before surgery, for adults with early-stage non-small cell lung cancer. This particular combination made by Bristol Myers Squibb is the first immunotherapy-based option before surgery for early-stage non-small cell lung cancer. It is given before surgery— in that neoadjuvant setting— to adults with non-small cell lung cancer to potentially help prevent it from spreading or reoccurring after surgery.
Danielle Hicks: Dr. Towe, could you tell us about the study that this information is based on?
Dr. Christopher Towe: Sure, I'd be happy to. But I am going to get into the weeds of technical jargon here. There are a lot of numbers that are important, but, that's the kind of thing that doctors like me care about. So, brace yourselves. The FDA approval was based on a clinical trial called CheckMate -816. Opdivo was studied in this clinical trial of 358 patients with early-stage non-small cell lung cancer, and all of them were candidates for surgery. 179 patients were given Opdivo and chemotherapy before surgery, while 179 other patients were given chemotherapy alone.
Danielle Hicks: What were the results?
Dr. Christopher Towe: Well, the trial showed that for patients who were treated with Opdivo and chemotherapy combination before surgery, the risk of cancer spreading or returning was reduced by 37 percent compared to chemotherapy alone. At 31.6 months, half of the patients with Opdivo and chemotherapy remained free of their cancer spreading or returning, compared to 20.8 months in patients on chemotherapy alone who were free of cancer spreading or returning. 31.6 is a lot more than 20.8, so in my practice I think of this as a real game-changer.
Danielle Hicks: Wow, this is really great.
Dr. Christopher Towe: Yeah, and additionally there's something called complete pathologic response. This means that there's no detectable tumor after surgery. In the CheckMate -816 trial, 10 times more patients who were given Opdivo and chemotherapy before surgery had a complete response compared to those on chemotherapy alone after the surgery. That would equate to 24 percent of patients on Opdivo and chemotherapy versus 2.2 percent of patients on chemotherapy alone.
Dr. Nisha Mohindra: Thanks for going through the numbers. It really is numbers like those that make all of us in this space so excited.
Danielle Hicks: Now you mentioned earlier that Opdivo is an immunotherapy. A lot of people may have heard about immunotherapy, but Dr. Mohindra, can you explain more about it and how it works?
Dr. Nisha Mohindra: Immunotherapy is a type of treatment that works with the person's own immune system to fight their cancer. It can help the immune system find and attack cancer cells, but it can also cause the immune system to harm healthy cells.
Danielle Hicks: I see. So, it sounds like an option for some patients, but not all.
Dr. Nisha Mohindra: Yes. Not all patients will respond to immunotherapy, and it may not be appropriate for all types of cancer. It is important that patients discuss potential benefits, as well as risks of immunotherapy with their medical team to determine the best course of treatment.
Danielle Hicks: Can you talk a little bit about the risks?
Dr. Nisha Mohindra: Yes of course. There are risks associated with any treatment. I'm going to throw a long list of side effects at you, which I know can be overwhelming, but I think it's important to know the scope of these treatments. Opdivo can cause problems that can sometimes be serious or life-threatening and can lead to death. Serious side effects may include problems with your lung; intestine; liver; hormone gland function; kidney; skin; problems in other organs and tissues; severe infusion reactions; and complications of stem cell transplant that uses donor stem cells, otherwise known as allogeneic transplant. The most common side effects of Opdivo when used in combination with chemotherapy include nausea, constipation, feeling tired, decreased appetite, and rash.
Dr. Christopher Towe: Yeah, and, Dr. Mohindra, I'm sure you'll agree it's important for patients to call or see their healthcare providers right away for any symptoms that they think are concerning.
Dr. Nisha Mohindra: Yes, absolutely. I think it's important to bring up side effects early and often. And these are not all of the possible risks associated with Opdivo. Please see the Important Safety Information for more.
Indication
OPDIVO® (nivolumab) is a prescription medicine used in combination with chemotherapy that contains platinum and another chemotherapy medicine, before you have surgery, for adults with early-stage lung cancer (called non-small cell lung cancer).
It is not known if OPDIVO is safe and effective in children younger than 12 years of age with melanoma or MSI- H or dMMR metastatic colorectal cancer.
It is not known if OPDIVO is safe and effective in children for the treatment of any other cancers.
Important Safety Information for OPDIVO® (nivolumab)
What is the most important information I should know about OPDIVO?
OPDIVO is a medicine that may treat certain cancers by working with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended. You may have more than one of these problems at the same time. Some of these problems may happen more often when OPDIVO is used in combination with another therapy.
Call or see your healthcare provider right away if you develop any new or worse signs or symptoms, including:
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with OPDIVO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include:
Getting medical help right away may help keep these problems from becoming more serious. Your healthcare team will check you for these problems during treatment and may treat you with corticosteroid or hormone replacement medicines. Your healthcare team may also need to delay or completely stop your treatment if you have severe side effects.
Possible side effects of OPDIVOOPDIVO can cause serious side effects, including:
The most common side effects of OPDIVO, when used in combination with chemotherapy, include: nausea; decreased appetite; feeling tired; rash; pain in muscles, bones, and joints; vomiting; constipation; and pain, tingling, or burning in your hands and feet.
These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist. You are encouraged to report side effects of prescription drugs to the FDA. Call 1-800-FDA-1088.
Before receiving OPDIVO, tell your healthcare provider about all of your medical conditions, including if you:
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start receiving OPDIVO.
Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements.
Please see U.S. Full Prescribing Information and Medication Guide for OPDIVO.
© 2024 Bristol-Myers Squibb Company
OPDIVO® is a registered trademark of Bristol-Myers Squibb Company
1506-US-2400405 10/24
Phase 3 Trial Begins In MRNA-Based Therapy Plus Keytruda In Non-Small Cell Lung Cancer
This trial will assess an individualized neoantigen therapy plus Keytruda in some patients with non-small cell lung cancer.
A Phase 3 trial is testing a new mRNA-based cancer therapy with Keytruda for non-small cell lung cancer.
The phase 3 INTerpath-009 trial has been initiated to evaluate an individualized neoantigen therapy plus Keytruda (pembrolizumab) in the adjuvant treatment of resectable stage 2, 3A or 3B non-small cell lung cancer whose disease did not completely respond to neoadjuvant Keytruda plus platinum-based chemotherapy.
Global recruitment has also started for this trial, with the first patients enrolling in Canada, according to a press release from Merck, the manufacturer of Keytruda, and Moderna, the manufacturer of the individualized neoantigen therapy V940 (mRNA-4157).
According to the release, individualized neoantigen therapies are typically created to elicit an antitumor immune response by creating T-cell responses based on the mutations present on a patient's tumor. A neoantigen, as noted by the National Cancer Institute, is a protein that develops on a cancer cell when specific mutations occur in tumor DNA that may play a role in aiding the body create an immune response against these specific cancer cells.
"While the overall survival rates for patients with non-small cell lung cancer have significantly improved in recent years, lung cancer contributes to be the leading cause of cancer death worldwide," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, in the release.
Glossary:Adjuvant treatment: additional treatment after the primary treatment to reduce the risk for cancer recurrence
Neoadjuvant treatment: the first treatment given to potentially shrink the tumor before the main treatment
Overall survival: the time when a patient with cancer is still alive
Pathological complete response: the lack of all indicators of cancer as determined by tissue samples removed after treatment
Distant metastasis: cancer that spreads from the original location to other lymph nodes or organs
mRNA: a type of RNA in cells that carry genetic information to create proteins
In the INTerpath-009 trial, researchers are aiming to include 680 patients with resected stage 2, 3A or 3B non-small cell lung cancer who did not achieve a pathological complete response to Keytruda plus platinum-based chemotherapy. Other specific eligibility criteria for this trial include an Eastern Cooperative Oncology Group performance status of 0 (fully active) or 1 (restricted activity), and no EGFR mutation, which is a genetic mutation that can be found in some patients with non-small cell lung cancer.
After undergoing surgical resection, these patients will be randomly assigned to receive either V940 plus Keytruda or placebo plus Keytruda.
The main areas of interest for researchers include disease-free survival (the time from randomization to any recurrence), an occurrence of a new primary non-small cell lung cancer or all-cause death, whichever occurs first, according to the press release. Other areas that researchers will focus on include distant metastasis-free survival, overall survival, lung cancer-specific survival, disease-free survival after initiation of the next line of therapy, quality of life and safety, according to the trial's ClinicalTrials.Gov listing.
"We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer, and together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy," said Dr. Kyle Holen, senior vice president and head of development, Therapeutics and Oncology at Moderna, said in the release.
The trial's listing on ClinicalTrials.Gov notes that the estimated primary completion date of this trial is May 16, 2033, during which the final data would be collected for the primary outcome.
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