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A recent study showed that undergoing molecular genotyping before receiving first-line treatment resulted in improved survival for patients with non-small cell lung cancer (NSCLC).

Molecular genotyping looks at the genetic makeup of a tumor. Specifically, within NSCLC, molecular genotype testing can reveal genes that contribute to the reason lung cancer grew into the disease.

In an interview with CURE®, Dr. Melina Marmarelis, Penn Medicine Physician, discussed the study further, alongside next steps that are being looked at within the specific patient population.

Q: Why is it beneficial for patients to undergo molecular genotyping?

A: The most obvious reason is that there is information in those testing reports that will actually determine which drug a patient gets. There are specific targets and those in lung cancer, for the most part, those are pills. Some examples of those are specific mutations in genes like EGFR, ALK or ROS1. And if a patient has one of those specific mutations in their tumor, then they're eligible for a targeted therapy, usually in the form of a pill that they take at home, to treat their cancer compared to chemotherapy or immunotherapy, which are different modalities of treatment. It's actually widely disparate, the type of treatment someone might receive, depending on those results.

Q: Are these therapies easily accessible to patients?

A: Even if you find the target, only about 50% of people actually get the appropriate drug. There are a lot of reasons for that probably, there are a lot of barriers, some patients may be too sick for any therapy. Some of the reasons that you're alluding to, in terms of financial barriers, are probably very real as well. These drugs are available and approved in the United States, they are covered by insurance, but there are often are hefty copays for patients. There are patient assistance programs that are relatively good, but actually recently have also undergone some changes that have made it a little bit harder for patients to access these drugs. I think they're still very much as an access problem.

Q: Is there any room for a future study to further help this patient population?

A: Yes, you would need to start with patients who have been diagnosed, and in one group provide a certain type of molecular testing and in the other group, a different type. Of course, this day and age, we would never randomize people to not getting molecular testing, just because it's so important. But there now are various ways that people are approaching this. Some people are doing only the blood test because it will result faster and then trying to do the tissue if they don't get the answers there. I think there certainly are studies that can be done in order to figure out the optimal type of sequencing.

We are focusing on making sure that everybody gets tested. That's the focus of our current trial. We're looking at ways to nudge patient teams, essentially, to make sure that they're getting, in particular, the blood test, since that does give you the results, the fastest is an easy thing for people to do. We believe that doing both the tissue testing and the blood tests at the same time actually gives you a better chance of detecting one of these targets. And alongside patients being eligible for a targeted therapy.

Q: Within this field, what have you seen as the biggest advancement from 2023?

A: The first answer to that is that if you've looked back just at the last 10 years, the approvals for targeted therapies, so these pills, targeting a very specific alteration in lung cancer have just exploded. And that is great news for our patients. Many of these patient populations have multiple pills available to them. Even if the first pill doesn't work, they have a second pill potentially, or another targeted therapy. And so there have been approvals for various different targeted therapies, even this year. I think that that's probably the most straightforward the easiest thing.

There is also a lot of work being done on how to improve access to molecular testing, how to improve access to targeted therapies, and that work has to be done at a bunch of different levels. It's got to be done at the level of the physicians’ level of the patient, the level of the payer, the insurance company and even the level of some of the regulations that are set by the government for the types of tests that can be done.

For more news on cancer updates, research and education, don’t forget to 

Obtaining molecular genotyping results before first-line treatment resulted in better outcomes for patients with non-small cell lung cancer, an expert explained.

Molecular Genotype Testing May Improve Lung Cancer Outcomes

Dr. Michael Grant discussing ROS1 lung cancer

ROS1-Positive NSCLC Represents a Targetable Mutation for New Therapies

ROS1-positive non-small cell lung cancer, a rare subtype of lung cancer, involves a mutation that therapies — some of which have been recently approved by the Food and Drug Administration — can target and result in potential tumor shrinkage, an expert discussed.

This rare lung cancer subtype constitutes approximately 1% to 2% of patients with non-small cell lung cancer. This cancer is characterized by a genetic event called ROS1 rearrangement or fusion. Interestingly, it tends to occur in patients without a history of smoking, challenging common perceptions of lung cancer. Detection of ROS1 rearrangements requires sequencing, a process examining the tumor's genetics for relevant mutations.

The significance lies in ROS1 rearrangement being a targetable mutation. Drugs have been developed that effectively kill cancer cells and shrink tumors. The 

approval of specific drugs for this purpose is crucial

, as not all patients respond to existing treatments. Developing more effective drugs, especially those penetrating the brain to shrink associated tumors, improves treatment outcomes and minimizes side effects.

CURE® spoke with Dr. Michael Grant, an assistant professor of medicine in the section of medical oncology at Yale School of Medicine in New Haven, Connecticut, to learn more about ROS1-positive non-small cell lung cancer and the importance of identifying that specific genetic mutation.

ROS1 rearranged or ROS1-positive non-small cell lung cancer is a subtype of lung cancer that is — makes up about 1 to 2% of non-small cell lung cancer. And it's a … really interesting subtype, because the cancer is driven by this genetic event, which is the ROS1 rearrangement, or ROS1 fusion, it's also called. And, you know, when — this typically happens in patients that are not — you wouldn't expect to have lung cancer. So people that don't have a history of smoking or have a history of very light smoking, so it doesn't really fit what I think everybody sort of thinks about when they hear about lung cancer.

The thing that's really important, is that you — first is that ROS1 rearrangements or these genetic events are found. So in order to find them in the lung cancer, you have to look for them. And the lung cancer has to be subject to something called sequencing, which is where you look at the genetics of the tumor and you try to find out if there's any mutations or genetic events that could be driving the cancer forward.

And so when ROS1 rearrangements, like I said, 1 to 2% of these tumors may have a ROS1 rearrangement. And the thing that's really important about it is that, you know, this is a targetable mutation. So there are drugs that have been developed, that are extremely, extremely effective at killing the cancer cells, and causing shrinkage of the tumors, and sometimes like, you know, really profound shrinkage.

It's important — this specific approval is extremely important because, you know, despite the fact that there are good drugs to target this disease, you know, not everybody responds to them. The more — the better drugs that we can develop, the more drugs that can get into places like the brain and cause shrinkage of brain tumors that may be related to the lung cancer, you know, the safer the drugs can be, so the better the side effect profile, the better that we can treat the disease.

An expert explained what ROS1-positive non-small cell lung cancer is and why it is important to identify mutations like ROS1 through genetic sequencing. 

The year 2023 has increased the use of robotic, minimally invasive surgery for lung cancer, decreasing the amount of complications and recovery time for patients with the disease, explained Dr. Mark Dylewski.

In a recent interview with CURE®, Dylewski, who is the chairman of thoracic oncology for the Miami Cancer Institute and director of thoracic surgery for the Baptist Health System, explained how he thought this new surgical technique was one of the biggest advancements in the field.

Additionally, Dylewski looked ahead to 2024, and noted that artificial intelligence — also known as AI — may play a bigger role in lung cancer surgery, though the implications that this may bring are still to be determined.

Can We Talk? Artificial Intelligence in the World of Cancer Care

Looking back on 2023, what would you say is one of the biggest advancements in the field of lung cancer surgery?

I think the most exciting thing about surgery is the introduction of robotics — (also known as) minimally invasive surgery. (We’re) using robotic technology and integrated computer imaging, and so forth. We're able to work with companies developing this devices to make it less invasive, through smaller incisions, fewer incisions, which transition to better outcomes, fewer complications or shorter hospital stays early recovery for the patient. That has really changed the dynamic in which way surgeons practice nowadays.

Can you further discuss how minimally invasive surgery can improve quality of life for patients with lung cancer, especially compared to the surgical techniques that were used years ago?

I think the quality of life has improved, 100-fold between traditional open surgery and now the most advanced robotic minimally invasive surgery. If you if you really look back and reflect upon why surgeons did in the past, it was largely a comfort thing for most surgeons that practiced 20 or 30 years ago — they were comfortable opening up the chest cavity to put their hands in there to be to be able to feel the anatomy to identify the anatomy, and to be able to do a surgery safely.

With the advent of better imaging, better MRIs, better CT scans better PET scans, we began to understand the anatomy and be able to visualize the anatomy without actually looking inside the chest and feeling the organs inside the chest. We were able to conceptualize the where the tumor was located based on imaging, and that allowed us to use smaller incisions, endoscopic surgery in order to accomplish the same type of surgery through a minimally invasive approach.

So robotics now has put a computer between the surgeon and the patient, and I don't think anybody in the United States could say that a cell phone doesn't make them a more efficient, probably a safer person when it comes to conducting their daily routine. So imagine putting a computer in front of a surgeon between a patient that only makes a surgeon better as long as they figure out the safe way to integrate that technology. And that's what computers and robotic surgery allow us to do.

I'll give you a perfect example. Just consider that many surgeons have a mild tremor, and when they're suturing or when they're nervous, that tremor may get worse. Well, a computer allows you to program that tremor out of the actual movements that the robots doing. So it makes things so much safer, and more precise when you're doing surgery as a surgeon.

What are you hoping to see for 2024 and beyond when it comes to lung cancer surgery?

I think artificial intelligence is probably going to play a big role, and it's too early to tell how big of a role that's going to be, but one of the challenges that we face as surgeons trying to train the next generation of surgeons who is really to be able to give the skill set that's necessary to younger surgeons, because as you probably will realize surgeons are no longer spending hours on end in the hospital, studying and doing surgery and taking care of patients … So you have to balance your training to your quality of life. I think that's where these artificial intelligence technologies are going to come into play, where they're actually your surgical assistant, if you will, perhaps talking to you in the system educating you about proper technique, what the anatomy is, it may help you visualize, or overlay the CT images into operatively in order to guide the surgeon and educate the surgeon and sort of expedite their sort of adoption of this new technology. I think that's where you were going to see the next advancements and surgical technique.

An expert discusses how the use of robotic surgery improves the lives of patients with cancer, and looks forward to advancements that may come in 2024 and  beyond. 

Robotic Lung Cancer Surgery Improves Quality of Life ‘100 Fold’ 

For lung cancer, standard treatment regimens include surgery, radiation, chemotherapy, targeted therapies and immunotherapy. However, utilizing next-generation sequencing for lung cancer before treatment may provide patients with the personalized treatment regimen they need, an expert told CURE®.

According to the National Cancer Institute, next-generation sequencing (NGS) is a method researchers use to analyze the building blocks of DNA and RNA fragments simultaneously to determine any changes in the genome or specific genes. The purpose of next-generation sequencing is to identify the cause of certain diseases, including cancer.

“Next-generation sequencing is a piece of the puzzle needed to understand what treatments are best for patients with lung cancer. There are other ways to perform sequencing, so next-generation sequencing is almost a descriptive term. It's kind of like having, (4G) phone service and upgrading to (5G) phone service,” Dr. Adam Fox, assistant professor of medicine in the college of medicine at the Medical University of South Carolina in Charleston, explained to CURE®.

“(Next-generation sequencing is) a new laboratory method that allows us to assess genetic alterations or biomarkers in a patient's lung cancer. The next-generation portion of it really has to do with its capacity, its ability to take a small amount of tissue and rapidly, and in a large quantity, assess these biomarkers that help dictate whether one treatment or another treatment is best for an individual patient,” he added.

Biomarker testing (a method that samples tissue, blood and other bodily fluids to analyze certain genes, proteins and molecules for drivers of cancer) and NGS testing (a form of biomarker testing) are important for patients with lung cancer.

“When you talk about the importance of biomarker testing and NGS tests, then the importance comes down to the emerging benefits of precision medicine for cancer in general, and especially in lung cancer. Biomarkers and precision medicine treatments are a constantly evolving field,” Fox noted.

“In general, it seems as though precision medicine therapies offer patients better outcomes. And to deliver these precision therapies, you have to look to see if patients will respond to them,” he said. “And that's what these biomarker tests or NGS tests (do). They assess, ‘Is this patient going to respond to this medication?’”

Comparing Small Cell and Non-Small Cell Lung Cancer

In terms of NGS’s current role in the treatment of lung cancer, Fox emphasized that it helps “select the best treatment” for patients.

“For most patients, (doctors) would like to have an assessment of these biomarkers for next-generation sequencing performed before (patients) receive any treatments to help guide the first and the best treatment,” Fox said. “In (most) cases, it helps triage people into what therapies to (receive). Again, at a metastatic stage, it dictates the first therapy.

“The therapy differences can be huge: if you are one of the smaller proportion of patients with a mutation found by NGS, you might only take a pill therapy for your cancer as the very first treatment for metastatic cancer. This is different from outcomes one may experience, especially when compared to chemotherapy.”

NGS’s future role in lung cancer treatment could potentially help welcome Food and Drug Administration (FDA) approvals for more targeted therapies, Fox said.

“For lung cancer treatment, it’s evolving every couple of years. So next-generation sequencing is this testing modality. It’s newer, it’s able to give us a lot of information in a relatively short amount of time,” Fox explained. “We expect over time that more targeted therapies specifically designed for what's driving people's cancers, to continue to expand. Each year since 2015, we've had one or two new biomarkers, which are detectable on next-generation sequencing, have new FDA-approved drugs.”

The role of NGS in the future for lung cancer can certainly benefit patients, especially regarding toxicities from treatments.

“For the future, we expect more. Tests need to be run on more genes because we'll hopefully continue to have more therapies to offer people,” said Fox. “Again, almost all of these targeted therapies are more desirable than chemotherapy, because they are often less toxic and more effective when biomarkers are matched with treatments. They each have their own side effects, (and those) are not all the same, but each in general has a safer side effect profile. In general, they each have better outcomes, including survival, and (fewer) side effects of the drug compared to chemotherapy.”

Undergoing next-generation sequencing before receiving treatment can benefit patients with lung cancer and their doctors, as one expert told CURE®.

Next-Generation Sequencing Helps ‘Select the Best Treatment’ for Lung Cancer

Lung cancer and pleural mesothelioma are often mistaken to be the same, but there are several factors that set them apart, experts told CURE®.

According to the Mayo Clinic, pleural mesothelioma is a rare type of cancer located in the tissue that surrounds the lungs, called the pleura. Although there are available treatments, research has yet to find a cure for pleural mesothelioma.

“Basically, (pleura) covers the lung like a rind of an orange, so it’s around the lung margins,” explained Dr. Moses Raj, a medical oncologist at the Allegheny Cancer Network Cancer Institute.

“(Pleural mesothelioma is) really from the lining and when you think about that, in comparison to lung cancer, lung cancer is a cancer of the tissue of your lungs. So, in other words, it’s the inherent lung tissue, not the lining of (the) lung cavity,” Dr. Ajaz Khan, a medical oncologist and enterprise chair of medical oncology at City of Hope Atlanta, Chicago and Phoenix, explained in a separate interview.

A main difference between lung cancer and pleural mesothelioma is the number of newly diagnosed cases every year.

“In the United States today, as of 2023, there were (approximately) a little over 230,000 cases of lung cancer diagnosed,” said Khan. “That’s in comparison to (pleural) mesothelioma, and there’s probably no more than about 3,500 cases per year. So, it's probably somewhere about an eight times higher level of lung cancer cases diagnosed per year than (pleural) mesothelioma.”

Knowing the characteristics of developing lung cancer and pleural mesothelioma is also important, notably because of the similarities and differences, according to Khan.

“We’ve seen more equivalency in terms of women being diagnosed with lung cancer as compared to men, so it’s almost become one-to-one,” he said. “But (the) majority of mesothelioma occurs in older men, and the usual age of diagnosis around the country on average is still around 72, and lung cancer is fairly similar (in) that most people are diagnosed in their early 70s as well.

“(For) lung cancer, we know about 80% to 90% of patients have smoked and developed lung cancer as a social risk hazard. In mesothelioma, it’s the exposure to asbestos (that) is one of the occupational hazards of developing this particular malignancy.”

When comparing lung cancer and pleural mesothelioma, there are also similarities in staging but key differences in terms of tumor location.

“Lung cancer and (pleural) mesothelioma both are similar in that we follow the TNM staging (a tool used to stage types of cancer) and both of them are in the lung,” Raj said. “Traditionally, (in stage one) lung cancer, for example, (there’s) a small tumor in the lung and you remove it. Mesothelioma is not like that, because it is not in one area: it is an inch thick all over all over the lung.”

Because pleural mesothelioma is interspersed around the lung, it cannot be simply removed through surgery the way lung cancer is, Raj elaborated, which results in different treatments between the two.

“Lung cancer in early stages, up until now, was (treated with) surgery and then surveillance. And multi-modality is in stage three, like radiation and chemotherapy and perhaps surgery,” Raj said. “And (in) stage four, it’s only systemic treatment.

“In (pleural) mesothelioma, even in (the) early stages, it’s not completely cured with just one modality; the results are not good with (just) one (treatment).”

Traditional treatment for patients with pleural mesothelioma, Khan said, involved surgically removing the entire surface of the lung if the disease is present on one side of the lung.

“The challenge has become where it starts to invade into the opposite side of the lung cavity. And then that becomes in some ways, marginally resectable or unresectable,” Khan explained. “And so that’s where systemic therapies like immunotherapy and chemotherapy do play a role.”

Lung cancer and pleural mesothelioma are often confused, so it’s important to understand the key differences between them, including tumor location and treatments.

Differences Between Lung Cancer and Pleural Mesothelioma

The recent approval by the Food and Drug Administration (FDA) of 

BRAF inhibitor Braftovi (encorafenib) and MEK inhibitor Mektovi (binimetinib) 

for the treatment for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation marked the latest advancement in the development and deployment of therapies designed to target specific genetic mutations of patients with cancer, as one doctor explained to CURE®.

“This is only a subtype of the those (patients with stage 4, also known as metastatic, lung cancer) which carry this special mutation called the BRAF V600E, so that's very specific and accounts for only 3% to 5% of lung adenocarcinoma,” explained Dr. Gene G. Finley, assistant professor at Drexel University of College of Medicine and medical oncologist at AHN Cancer Institute, Allegheny Clinic Medical Oncology.

Finley explained the science behind BRAF mutations and what unmet needs still remain for this population of patients.

Q: Can you tell me a bit about the BRAF mutation and why that is something that researchers are targeting in lung cancer treatment?

 All human cells, and cancer cells included, respond to signals and most of these signals occur in a variety of ways, but … for the most part, these genes such as BRAF are involved in a process that is called signal transduction. What signal transduction refers to is the transmission of signals from outside the cell to inside the cell and ultimately to the nucleus. So, the prototype signaling occurs as follows: a hormone, especially a peptide hormone, will bind to a receptor that sticks outside of the cell. When that happens, then this triggers an enzyme activity inside the cell on that receptor molecule and generally that enzyme activity is called a protein tyrosine kinase, with some exceptions. But for the most part, then that enzyme works on another protein inside the cell, and then that protein then becomes activated and it signals a next protein downstream.

And the upshot of it is that after this signaling occurs, it reaches a signaling molecule which goes into the nucleus, and then activates some gene or genes within the DNA, which then cause other genes to be expressed that, for example, will tell the cell to grow or divide. And so, that’s the most common form of signaling that we see in cancer, from the outside to the inside through a number of different signal transduction pathways. And basically, we’re using these proteins to send signals from the outside of the cell to the inside of the cell, and for the most part, these signals tend to make the cells grow, not exactly faster, but for more of the cells to be growing and dividing at any one time.

So, that's probably the simplest way to look at it. These are signals that lead to cell proliferation, or in the case of cancer cells, to cancer cell division and growth.

Q: Regarding this specific population of patients with non-small cell lung cancer with the BRAF mutation, what needs remain now that this treatment option is on the table?

Well, these kinds of drugs are relatively well-tolerated, but they still have side effects. So, typical things like tiredness, nausea, diarrhea, etc. can occur in 15% to 20% of patients, and some people have to stop the drug because of side effects.

Following the recent FDA approval of Braftovi with Mektovi for some patients with NSCLC and a BRAF V600E mutation, a lung cancer expert explains the science behind the news.

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