What is Lung Cancer? Symptoms, Treatment, More
FDA Approves New Drug For Non-Small Cell Lung Cancer With ROS1 Fusions
Ingrid Adams, now 68, has been coping with metastatic lung cancer for more than a decade. Standard treatment — including chemotherapy and radiation therapy — kept her disease under control for a while, but the cancer continued to spread. Everything changed when she came to Memorial Sloan Kettering Cancer Center (MSK) in 2017 and was given the opportunity to participate in a phase 1 clinical trial (research study) for a targeted therapy called repotrectinib (Augtyro™).
Six years later, the cancer has shrunk substantially, and her disease has remained stable ever since.
The drug Ingrid was given was approved in November 2023 by the Food and Drug Administration (FDA) to treat advanced non-small cell lung cancer with a ROS1 fusion. The approval was based on findings from the trial in which Ingrid was one of the very first patients.
The study, called TRIDENT-1, was a phase 1/2 trial that enrolled 127 patients around the world. The results are being published in The New England Journal of Medicine on January 11, 2024. The first author of the paper was Ingrid's doctor, MSK thoracic oncologist and early drug development specialist Alexander Drilon, MD.
Investigators reported encouraging results:
"This drug is a win on many fronts," says Dr. Drilon, who is Chief of the Early Drug Development (EDD) Service at MSK. "Repotrectinib not only has a good chance of working well but it can work for a very long time, possibly longer than other approved treatments." He explains that MSK was involved in the development of repotrectinib from the very early stages, including some of the studies that showed how the drug works in the brain as well as the body, and how it works in tumors that are resistant to other drugs.
MSK has now treated close to 50 patients with repotrectinib across all clinical trials. As one of the first people enrolled in the study, Ingrid has now been on the drug longer than any other patient — for more than six years.
What Are ROS1 Fusions in Cancer and How Does Repotrectinib Target Them?Repotrectinib works by targeting an error in cells called a ROS1 fusion. The ROS1 defect occurs when a piece of one gene breaks off and attaches to another unrelated gene. In turn, the defect causes cells to grow out of control and form tumors. ROS1 fusions are found in between 1% and 2% of lung cancers. They are detected with tumor sequencing tests like MSK-IMPACT®. They also occur in other cancers, including glioblastoma, a type of brain cancer, and cholangiocarcinoma, also known as bile duct cancer.
Research on the drug is ongoing and includes trials for both adults and children with other types of cancer caused by ROS1 fusions. It is also being studied in cancers caused by NTRK fusions, another of the drug's targets.
People With Lung Cancer Can Respond Well to Repotrectinib, but Unique Side Effects Should Be MonitoredRepotrectinib is not the first drug to target ROS1 fusions. The FDA previously approved two other drugs, crizotinib (Xalkori®) and entrectinib (Rozlytrek®). But crizotinib and entrectinib may work for a shorter time than repotrectinib before the tumors evolve and begin to develop resistance. Furthermore, many patients whose cancers develop resistance to crizotinib or entrectinib can still respond to repotrectinib. Before getting repotrectinib, Ingrid had received crizotinib, but it stopped working after only seven months.
Clinical trials nurse Kaitlin Balbo (left) and nurse practitioner Virginia Ferreira (right) take care of patients enrolled in clinical trials at MSK, including Ingrid.
"Advances in the treatment of lung cancer have really exploded in the past few years," says Kaitlin Balbo, MSN, RN, a clinical trials nurse who is part of the EDD team. "In addition to repotrectinib, we are also able to offer other new therapies to many people with lung cancer. These options, including a newer ROS1 inhibitor that may work after repotrectinib, were not available at the time Ingrid was first diagnosed."
Most patients tolerate repotrectinib well, but dizziness is a common side effect, and patients who are sensitive to it may need a lower dose. About one in three patients on the clinical trial had to take a lower dose because of dizziness or other symptoms.
Other side effects are a metallic taste in the mouth, a burning sensation in the limbs, and weight gain over time. Serious side effects are less common and include muscle breakdown and liver or lung inflammation. Only 7% of patients had to stop taking the medicine because of side effects. Ingrid says she had tingling in her hands and fingers when she first started taking the drug, but not so much anymore since her dose was cut from four to two pills. She continues to take the pills every day.
Grateful for a Clinical Trial and Compassionate CareThe idea of taking an experimental drug didn't make Ingrid nervous. "I was just grateful my doctors found something that could help me," she remembers.
Ingrid says she's bonded with several members of her team involved in the trial, especially nurse practitioner Virginia Ferreira, DNP.
"Because we see patients in clinical trials so frequently, we develop strong relationships with them," Dr. Ferreira says. "Having significant trust in us is important because, in some cases, we are asking people to take drugs that have never been given to humans before."
Ingrid and Dr. Ferreira have developed a close relationship during the six years Ingrid has been receiving care at MSK.
Ingrid appreciated how her team went above and beyond to take care of her. She had been having problems with a swollen knee for a long time, due to years working as a home health aide. After ordering scans to confirm the problem was not related to her cancer, Dr. Ferreira helped arrange for Ingrid to see an orthopedic specialist. It turned out to be a torn meniscus, which was surgically repaired in April 2023 at a local hospital near Ingrid's home.
"At MSK, we always focus on the whole patient," Dr. Ferreira says. "We feel fortunate to see patients' health improve to the point that many of them — even those who are very sick when they first come to see us — are able to go back to living full lives."
Funding and Disclosures
This trial was funded by Turning Point Therapeutics and Bristol Myers Squibb, which make repotrectinib.
Dr. Drilon has relationships with or financial interests in A.C. Camargo Cancer Center; AbbVie; Answers in CME; Associazione Italiana Oncologia Toracica; Bayer; Boundless Bio, Inc.; Clinical Care Options; Clinical Education Alliance, LLC; Didactika s.R.L.; EcoR1 Capital, LLC; Elevation Oncology, Inc.; InnoCare Pharma Inc.; Korean Society of Medical Oncology; Lung Cancer Research Foundation; MBrace Therapeutics, Inc.; MI&T s.R.L. Organizzazione Congressi; MJH Life Sciences; Medscape; Monte Rosa Therapeutics, Inc.; PeerView Institute for Medical Education; Physicians' Education Resource; Projects In Knowledge; Springer Nature Group; Total CME; Treeline Biosciences, Inc.; Universidad Autónoma de Madrid; Vindico Medical Education; and i3 Health.
WTOP's Neal Augenstein: My 2024 Resolution, Living With Stage 4 Lung Cancer
WTOP's Neal Augenstein says 2023 was a great year, despite starting it with stage 4 lung cancer. But, what's in store for 2024?
By now you know, after one-pill-a-day targeted therapy, and a robotic-assisted lobectomy, I've been cancer-free since the end of April.
But, what's in store for 2024?
In a few weeks I'll have a new type of test for the first time — a liquid biopsy — that can provide some clues of what my future treatment, and perhaps prognosis, will be.
Scientists and doctors have long said that stage 4 lung cancer isn't curable, but within the last decade it's becoming increasingly treatable.
Lung cancer is the leading cause of cancer deaths in the United States, with one of the lowest five-year survival rates, because cases are often diagnosed at later stages, when the disease is less likely to be curable.
However, recent improvements in personalizing treatments to a person's exact type of cancer are helping people live longer, and with a better quality of life.
According to the American Lung Association's "State of Lung Cancer 2023" report, "The national average of people alive five years after a lung cancer diagnosis is 26.6%, which is a 22% improvement over the last five years."
Current research shows that while my particular kind of cancer mutation, positive for the epidermal growth factor receptor, or EGFR, reacts well to the targeted therapy, there's also a high likelihood of cancer recurrence, when the targeted therapy stops working.
I have to keep reminding myself that my treatment may change, in the near or distant future, since my current side effects from a daily pill of osimertinib have been so minimal: acne-like rash, cracked skin on my fingertips and the need for a daily nap.
Shortly after my lobectomy, in April 2023, when I became NED — no evidence of disease — my oncologist recommended that my "surveillance plan will be similar to someone with active cancer, given that we have to remain vigilant."
So far, that vigilance has consisted of a CT scan every three months, and monthly blood work to ensure that I'm tolerating osimertinib, which has the brand name Tagrisso.
The CT scans, which can find lesions as small as two or three millimeters, have all been great, showing no new areas of concern in my lungs or elsewhere in my body.
What is a liquid biopsy, and why have one?My EGFR diagnosis was based on biomarker testing of a tiny piece of tumor tissue from my left lung, taken during a bronchoscopy in November of 2022. The liquid biopsy, which is simply a blood test, will be a "where are we today, and should we be making changes for tomorrow" snapshot of my current biomarkers.
When a cancerous tumor is active, it sheds into the bloodstream, which often spreads — or metastasizes — to lymph nodes or other parts of the body.
Despite the effectiveness and typically less severe side effects of targeted therapies, compared to chemotherapy, tyrosine kinase inhibitors (TKIs) eventually stop working.
Remaining cancer cells can change as they continue to grow — often called a rearrangement, fusion or amplification — which makes them resistant to the TKI.
That's why I'm having the liquid biopsy: to see whether there are still cancerous cells in my bloodstream, and whether they have become altered from my original diagnosis, of EGFR 19 deletion, because that would indicate a higher likelihood of recurrence and spread, either in my lungs or other parts of my body.
So, that's my resolution for 2024 — to aggressively monitor real-time changes in my DNA, through liquid biopsies, even before any areas of concern might show up on a CT scan.
While the thought of cancer returning is scary, the good news is resistance to TKIs is so common that lots of clinical trials are testing ways to treat lung cancer after resistance.
In some cases, a small tumor or two can be removed with surgery or radiation. In the event of more prevalent spread, in addition to chemotherapy, other options would include repeating biomarker testing, to see if a new tumor had a different targetable mutation, as well as immunotherapy.
I'm looking forward to a happy, healthy 2024, enjoying my family, friends, my 27th year at WTOP, and being a good patient, all while learning more about my lung cancer and remaining hopeful about the new treatments that are just around the corner.
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B.C. Researchers Developing Breath Test For Lung Cancer
Doctors Stephen Lam and Renelle Myers are leading a research team in B.C. That is using AI to help develop a breath test for lung cancer. (Golnaz Sadjadi/B.C. Cancer Foundation)
Marla Kott was diagnosed with Stage 4 lung cancer on Nov. 21, 2014. It was her 60th birthday.
"It was not a great day," said Kott, who was was one of thousands of people in Canada diagnosed with lung cancer that year.
The disease accounts for a quarter of cancer deaths, according to the Canadian Cancer Society. The society says the five-year survival rate is 62 per cent for those diagnosed with Stage 1 lung cancer, and drops to three per cent for Stage 4.
It took about a year for Kott to be diagnosed, after undergoing numerous tests to determine what was wrong.
A lung X-ray of a cigarette smoker in an undated photo. (American Cancer Society/Getty Images)Against the odds, Kott is still going strong nine years later — but the Vancouver resident wishes there had been a way to detect her cancer sooner.
"I might have been able to have surgery and be done with it," she said, imagining scenarios in which the disease was discovered early and fully treated.
"I wouldn't be on drugs or living with it or being tested a lot. I would have been cured, so to speak. Now I will never be cured. I will always have cancer."
Researchers with B.C. Cancer in Vancouver are now working to develop a breath test that could help show signs of cancer earlier, and screen more people, more easily.
"When we exhale, we exhale over 1,000 volatile organic compounds," said team co-lead Dr. Renelle Myers, adding that some of these compounds have the potential to indicate cancer development.
Myers first began studying breath samples in 2020, when she opened what she says is the first clinical breath lab in Canada. When the pandemic hit, her team pivoted from cancer research to looking at the detection of COVID through breath.
"If we can find that fingerprint of an early lung cancer, that will help us screen, much more easily, many, many people around the province and around the world."
Additionally, researchers hope the test will help them understand how changes in the lungs might indicate cancer development in people who have never smoked.
"We are seeing an alarming increase of lung cancer in never-smokers," Myers said.
A study published by B.C. Cancer in June 2023 found that 33 per cent of lung cancer patients in Vancouver had never used tobacco products, and suggested air pollution might be the cause — in particular, a particle called PM2.5, levels of which are higher in B.C. During wildfire season.
The test researchers are working on uses artificial intelligence to sift through data.
"There's thousands of compounds in a single breath," Myers said, adding that AI helps organize people by age, risk factors and other indicators of cancer.
"Even if our team works 24/7, we couldn't process all the samples required for these large, multi-centre studies with only the system we have now," research team co-lead Dr. Stephen Lam said. "Especially since samples can't be stored for very long once collected."
Currently, the best way to diagnose lung cancer is through a CT (computed tomography) scan, Myers said. But other tests, including blood tests, X-rays, MRIs, ultrasounds and biopsies, to name a few, can be part of the determination.
"The majority of patients who are diagnosed with lung cancer are diagnosed at a late stage when they become symptomatic," Myers said.
The team is in the early stages of nationwide clinical study, having collected nearly 300 samples from individuals in Ontario, B.C. And Quebec. The goal is to look at samples from 4,000 people.
They're looking at pulmonary nodules — small clumps of cells in the lungs — that are often benign but can develop into cancer.
Researchers will follow patients over five years to see how those nodules develop and how breath signatures change in turn.
By being able to identify if a nodule is not cancerous, Myers said patients could be given the all clear, and not have to follow up for several months.
"It's powerful in that it could potentially really reduce downstream resource utilization in our health-care system," she said.
The Early Edition8:35B.C. Researchers using A.I.-powered breath tests to detect lung cancer
New technology out of B.C. Aims to detect lung cancer earlier, ultimately saving lives. Researcher Dr. Renelle Myers explains.
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