Progress in Early-Stage Non-Small Cell Lung Cancer Treatment

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:

• Lung problems: new or worsening cough; shortness of breath; chest pain
• Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; severe stomach-area (abdominal) pain or tenderness
• Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); bleeding or bruising more easily than normal
• Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heart beat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
• Kidney problems: decrease in your amount of urine; blood in your urine; swelling in your ankles; loss of appetite
• Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in the mouth or nose, throat, or genital area

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:

• Chest pain; irregular heartbeat; shortness of breath; swelling of ankles
• Confusion; sleepiness; memory problems; changes in mood or behavior; stiff neck; balance problems; tingling or numbness of the arms or legs
• Double vision; blurry vision; sensitivity to light; eye pain; changes in eye sight
• Persistent or severe muscle pain or weakness; muscle cramps
• Low red blood cells; bruising

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 OPDIVO
OPDIVO can cause serious side effects, including:

• See “What is the most important information I should know about OPDIVO?”
• Severe infusion reactions. Tell your healthcare team right away if you get these symptoms during an infusion of OPDIVO: chills or shaking; itching or rash; flushing; shortness of breath or wheezing; dizziness; feel like passing out; fever; back or neck pain
• Complications of bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be severe and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with OPDIVO. Your healthcare provider will monitor you for these complications.

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:

• have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
• have received an organ transplant
• have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
• have received radiation treatment to your chest area in the past and have received other medicines that are like OPDIVO
• have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• are pregnant or plan to become pregnant. OPDIVO can harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if OPDIVO passes into your breast milk. Do not breastfeed during treatment with OPDIVO and for 5 months after the last dose of OPDIVO.

Females who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start receiving OPDIVO.

• You should use an effective method of birth control during your treatment and for 5 months after the last dose of OPDIVO. Talk to your healthcare provider about birth control methods that you can use during this time.
• Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with 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.