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Patients with moderate to severe depression may have elevated inflammatory biomarkers shown to predict survival in lung cancer, according to recent study results.

Both lung cancer and depression have properties of inflammation, which is the body’s response to injury or infection. Chronic inflammation can damage healthy tissues, cells and organs over time. It may also affect how patients respond to treatments like immunotherapies and targeted therapies, which utilize the patient’s immune system.

Findings from the study, which were published in 

, highlight the importance of screening for and treating depression and anxiety in patients with lung cancer.

“For patients and caregivers, it is important that practices and facilities screen their loved one for depression and anxiety,” Barbara L. Andersen, professor of psychology at The Ohio State University in Columbus, said in an interview with 

. “Screening has been mandated by the Commission on Cancer, so it is important for patients and caregivers to prompt the medical team if screening has not been done. Once screened, it is important for patients (to) take to heart any recommendations for further assessment and provision or referral for treatment for their depression or anxiety.”

The study that Andersen and colleagues conducted included 186 patients with newly diagnosed stage 4 non–small cell lung cancer (NSCLC) who were screened for depression and anxiety at diagnosis and before treatment began. Researchers then used medical record data from blood draws at diagnosis, abstracting cell counts of neutrophils, lymphocytes and platelets. The counts were used to calculate three inflammation biomarkers, such as the ratio of neutrophils to lymphocytes.

“Being aware that both depression and lung cancer have inflammatory properties, we predicted significant effects between the severity of depression at diagnosis and increased systemic inflammation,” Andersen said.

Patients were followed, and analyses confirmed that the three biomarkers predicted two-year overall survival (the time when a patient is still alive) of the patients, which was 61%. As expected by the researchers, predictors of worse overall survival were higher neutrophil-to-lymphocyte ratio (which indicates an inflam- matory imbalance of the tumor; NLR), higher platelet-to-lymphocyte ratio (an indicator of tumor progression; PLR) and lower advanced lung cancer inflammation index (ALI; a way to assess ongoing inflammation).

Researchers tested the link between the three biomarkers and depressive symptoms. Findings demonstrated that patients with moderate or severe depressive symptoms were two to three times more likely to have poor biomarker levels.

Andersen noted that although this study focused on patients with NSCLC, it would be anticipated that significant biomarker/depression relationships would be found in patients with small cell lung cancer.

“These biomarkers — NLR and PLR — are used across tumor sites and have been predictive of survival,” she said. “The markers are not unique to lung cancer, with only ALI being lung cancer-specific. I am confident that this same effect of elevated inflammation and depression severity would be found in patients with small cell (lung cancer).”

Andersen added that she does not want people to discount depression in patients with NSCLC.

“I’ve heard people say, ‘Well, they have cancer; of course they’re depressed.’ Well, no,” she said. “(Most patients with) cancer — 70% (or) 80% of them — do not have moderate to severe symptoms. But then there’s everyone else — about 30% — (who) do have severe symptoms of depres- sion, perhaps major depressive disorder. When severe and untreated, depression is a mental health problem that shows little with time. More likely, it will continue at this level.”

Based on the findings from this study, Andersen recommended patients with NSCLC seek treatment for depression, if it is offered.

“I know that’s hard for people with depression to follow through. A symptom of depression is low motivation,” she said. “That can feed into reluctance to take a referral for care or begin psychological treatment. Major depression is an insidious illness with toxic effects when left untreated. Fortunately, there are efficacious treatments for both depressive and anxiety symptoms, with the strongest evidence for cognitive behavioral therapy and behavioral activation.”

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The inflammation associated with lung cancer and depression may impact survival, despite treatments like immunotherapy and targeted therapies. 

Inflammatory Biomarkers From Lung Cancer, Depression May Predict Survival Outcomes

When patients are undergoing treatment for lung cancer, the expected focus is on treatment options and details. Patients and their families may be surprised when the topic of supportive or palliative care enters the conversation with their cancer team. Patients may assume that supportive or palliative care means end-of-life care, when in fact it is meant to improve a patient’s quality of life during treatment.

For example, supportive care commonly addresses physical symptoms associated with lung cancer and side effects associated with cancer therapy. These include cough, shortness of breath, pain, loss of voice and difficulty swallowing, nausea and diarrhea, among others. And palliative care often focuses on the social, emotional and financial effects of the disease to boost a patient’s well-being.

These types of care are meant for patients with lung cancer regardless of their age, the stage at which their cancer was diagnosed and the treatment they are receiving. Most guidelines from major oncology organizations, which are based on available evidence from studies, recommend the initiation of supportive and palliative care at the time a patient received a lung cancer diagnosis so symptoms can be addressed before they potentially become debilitating. 

In fact, even aggressive treatment goes hand-in-hand with these types of care: Studies have shown that when such care is initiated early, patients live longer. Patients who receive it tend to have a better quality of life and outlook.

Sometimes patients with lung cancer do not start supportive or palliative care at the so-called right time because either they are not told of the benefits soon enough or there is some hesitancy by the patient to start this type of care because they are mainly focused on their cancer treatment.

, we hope that you learn more about the benefits of both supportive and palliative care and how more efforts are being made to make such care more widely available.

Supportive care commonly addresses physical symptoms associated with lung cancer and side effects associated with cancer therapy.

Taking Cancer Support to a New Level

Anna Bass, 62, of Victoria, Virginia, had been a longtime smoker, so she was not surprised in October 2016 when she was diagnosed with adenocarcinoma in her right lung. Her doctor had noticed a small spot on a CT scan two years earlier after she quit smoking. She had opted to hold off treatment, hoping that the lesion would not grow larger.

Bass, a secretary at Victoria Baptist Church, underwent a lobectomy to remove the top right lobe of her lung. She was happy to learn that she required no further treatment. 

“My brother-in-law is an oncologist, and he said if they didn’t tell me to get chemotherapy or radiation therapy, it was because they weren’t necessary,” Bass recalls.

Throughout her cancer journey, Bass received an array of supportive care from her medical team, friends and family. Nurses addressed her pain, helped her learn to breathe properly again and demonstrated how to use an oxygen concentrator. She was encouraged to exercise, so she started walking.

But the most significant support Bass says she received from her care team was reassurance that her cancer had a good chance of being eliminated and likely would not reoccur. 

“They told me that the cancer had been slow growing, the biopsy had clear margins and they would be following me for the rest of my life,” Bass says. “Today I’m cancer free.”

Bass’s story illustrates the many benefits of supportive care for patients with lung cancer, a population that tends to skew older and have more comorbid conditions than those with other forms of cancer. Bass, for example, has chronic obstructive pulmonary disease and is a recovering alcoholic, which restricts her use of opioids to alleviate pain. 

When started early in the treatment continuum, guidelines show, supportive care can help patients live longer, improve their quality of life and cope better with the side effects of their disease and treatment, as well as comorbid conditions.

The terms supportive care and palliative care are sometimes used interchangeably, but there can be differences. The Multinational Association of Supportive Care in Cancer defines supportive care as “the prevention and management of the adverse effects of cancer and its treatment. This includes management of physical and psychological symptoms and side effects across the continuum of the cancer experience from diagnosis through treatment to posttreatment care.”

Palliative care, according to the Center to Advance Palliative Care, is “specialized medical care for people living with serious illnesses. It is focused on providing patients with relief from the symptoms and stress of a serious illness — whatever the diagnosis. The goal is to improve quality of life for both the patient and the family.”

Lung cancer is a prevalent disease with a high incidence rate, so it has received a lot of attention from researchers over the years. This has led to advances in treatment and supportive care. 

“This patient population still has a lot of needs, but the good news is that their prognosis and their experience have gotten better,” says

Dr. Jennifer Temel, co-director of Massachusetts General Hospital’s Cancer Outcomes Research and Education Program and professor of medicine at Harvard Medical School in Boston. 

“Targeted therapies and immunotherapy have (become) more effective, so patients are living longer. And for the most part, the physical symptoms associated with these treatments are less. This doesn’t obviate the need for supportive and palliative care for lung cancer patients, but I think their needs have changed over time and they are becoming more like other advanced cancer populations.”

Supportive and palliative care for patients with lung cancer commonly involve the entire care team, observes Betty Ferrell, director of nursing research and education and a professor at City of Hope in Duarte, California. A care team includes physicians, nurses, social workers, physical therapists, occupational therapists, nutritionists, chaplains, psychologists and psychiatrists. Other aspects may include such novel approaches as music therapy, art therapy, acupuncture and massage.

“There are four key disciplines in (patient) care: medicine, nursing, social work and chaplaincy,” Ferrell says. “Physicians evaluate the patient’s medical condition, while nurses do a lot of symptom management and handle other responsibilities. The social worker assists the patient and family with issues such as finances, transportation, and in-home services — you can’t provide good palliative care without a social worker. And chaplaincy addresses the patient’s spiritual needs. Chaplaincy is critical.”

Dr. Arif Kamal, chief patient officer with the American Cancer Society and an associate professor of medicine and population health sciences at Duke University School of Medicine in Durham, North Carolina, agrees that spiritual support is vital. 

“Chaplaincy can help when patients have existential questions, such as ‘Why did the cancer happen to me? I’ve always been a good person,’” he says. “That question usually does not have a scientific answer, but a chaplain can be very helpful in helping the patient work through it.”

On the medical side, supportive and palliative care can address symptoms unique to patients with lung cancer, Kamal adds. These include shortness of breath, cough, difficulty swallowing, loss of voice, coughing up blood, confusion and issues around brain metastases.

Almost all accepted treatment guidelines recommend that supportive and palliative care be started at the time of diagnosis in order to address the symptoms and side effects of treatment before they become debilitating. However, this often is not the case, Ferrell says. 

“When people come to us with lung cancer, everyone is focused on treating the cancer — no one wants to talk about palliative care,” she explains. “Everyone’s response is, ‘It’s not time yet, let’s just start chemotherapy, then maybe later we’ll start palliative care.’ As a result, patients may not receive the supportive care they need until months after they should have. By the time they receive it, their quality of life has been severely impacted.”

Temel says, “We as a research and clinical community still have to find that sweet spot of figuring out how and when to integrate palliative care at the best time. But based on the data, early integration of palliative care for patients with challenging physical or psychological symptoms is still the best strategy.”

According to Temel, Massachusetts General Hospital was among the first institutions to demonstrate the benefits of initiating supportive and palliative care at the time of diagnosis. 

“More than a decade ago, we published a paper that showed that when you involve palliative care early in the course of illness for patients with incurable lung cancer, they have a better experience with their cancer and have better outcomes,” she notes. “They have better quality of life, fewer symptoms of depression, spend less time receiving chemotherapy and have better outcomes at the end of life.” 

Whereas a patient’s care team addresses the physical and emotional impacts of treatment, friends and family also play a critical role in supportive care. But there is always the risk of burnout. 

“If you’re caring for someone with lung cancer, you’re a 24-hour caregiver,” Ferrell says. “That can be a huge burden on some family members.”

Lisa, who asked that her last name not be used, is a writer and publisher in Raleigh, North Carolina. She was a caregiver for her older sister during her lung cancer journey starting in 2014. She assisted her sister with everything from housing and meals to transportation to and from treatment. 

Although she was happy to help, Lisa admits that the two years of caregiving were extremely stressful.

“There were times when my sister could be so critical that it was hurtful,” Lisa recalls. “Things were so hard at times that my goddaughter and I would go away so I could regain my composure. We would have a vent session and try to reboot my compassion meter.”

The family caregiving experience was far less dramatic for Christy Dawkins, 51, of Batesburg-Leesville, South Carolina. When she received a diagnosis of stage 3 non-small cell lung cancer in December 2019, her husband enthusiastically jumped into the role of caregiver. He took a monthlong sabbatical from work to care for her, doing all he could to keep her spirits up. 

“He was there for me through all of the trips to receive radiation treatment and everything,” Dawkins says. “He really helped me through it.” Meanwhile, family friends created a meal train on Facebook so that the family wouldn’t have to worry about cooking during such a stressful time. 

We had people dropping off meals every night,” Dawkins recalls. “That was a huge help.”

Because lung cancer is more commonly diagnosed in older people, many family caregivers are older themselves and may be dealing with their own health issues, such as diabetes, heart failure and arthritis, Ferrell says. But their involvement can be extremely important to the patient. They are an additional pair of eyes and ears, and they often are directly involved in making sure the patient receives the care they need. 

But the heaviest burden they may bear is managing the patient’s emotional symptoms.

“We often don’t realize the role that caregivers play in helping patients
to keep going despite depression or anxiety,” Ferrell notes. “There’s a lot of fear, anxiety and emotions associated with living with lung cancer.”

Though supportive care for patients with lung cancer has been an integral part of treatment for many years, misconceptions still persist. 

“Most common is the belief that palliative care and hospice are synonymous, so that when we talk about palliative care, sometimes patients and their  families have worries that that means they’re at the end of life,” Temel explains. “It’s up to doctors, nurses and social workers to explain the distinction between palliative care and hospice care and the role of both services to allay those fears so patients are more accepting of the involvement of palliative care.”

“There must be educational campaigns that teach people how the emphasis during these conversations is not on end-of-life planning,” he says. “In my clinical practice, most patients are not dying. I have a large number of patients who have been seeing me for years because what we’re talking about is long-term distress, as opposed to an acute end-of-life type plan.”


Ideally, supportive and palliative care discussions are initiated by the patient’s medical team at the time of diagnosis. If that doesn’t happen, the patient and family caregivers should inquire about needed services, Ferrell says. “If my spouse or a parent is diagnosed with lung cancer, what do I want as a spouse or daughter? I want them to receive the best care possible,” she says. “So that’s the question every patient and caregiver should ask: ‘What about palliative care?’”

Concludes Temel: “I often remind my patients and their families, especially if I think they would benefit from something like palliative care but are resistant, that having cancer is hard for everyone and they should at least be open to accepting any support we can give them. Patients and their families talk about how it takes a village on their side to get through a cancer diagnosis. But it also takes a village on the clinician side. As an oncologist, I’m always going to do whatever I can to support my patients and their families. But the struggle is significant, so I rely on my colleagues who are social workers, nutritionists and psychologists to help out. Patients should take advantage of all of the services we have to help them navigate this very challenging time in their life.”

More awareness is needed to understand the benefits of both supportive care and palliative care in lung cancer.

Early Supportive Care Extends Life, Eases Cancer Symptoms

Patients with stage 1A non-small cell lung cancer (NSCLC) who undergo surgery to remove a small portion of their lung have outcomes comparable to patients who have surgery removing an entire lobe, according to recent study results.

 showed that patients with stage 1A NSCLC can benefit from having less lung tissue removed, one of the study’s researchers explained that patient selection is critical before making this decision.

“In a group of patients where the cancer is less than 1 inch ... and is near the edge of the lung, you can go in and biopsy the lymph nodes to make sure that the lymph nodes are clean,” Dr. Nasser Khaled Altorki, chief of thoracic surgery at Weill Cornell Medicine and NewYork-Presbyterian Hospital, said in an interview with 

. “If the lymph nodes are clean of cancer, then it’s OK to take a section of the lobe, not the whole (lobe). ... So you biopsy the lymph nodes first and make sure that these are small tumors and near the edge of the lung.”

Researchers sought to determine whether outcomes would differ if patients with stage 1A NSCLC underwent a wedge resection (a procedure to remove a tumor with a margin of tissue around it) versus having a lobectomy (removing a whole section of the lung).

“Make believe that you’re in an apartment, which is the lobe, and the apartment has rooms,” Altorki explained. “Each room is a segment, or you can take a part of the room, which is a wedge. So either one of those is acceptable and results in similar survival or freedom from cancer recur- rence as taking the whole lobe.”

In this phase 3 trial, researchers analyzed data from 697 patients with stage 1A NSCLC, meaning that their tumor was no bigger than 2 centimeters. Patients were randomly assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients) after it was confirmed that their disease had not spread to nearby lymph nodes.

Researchers focused on several outcomes, including disease-free survival (time between being randomly assigned and either disease recurrence or all-cause death), overall survival (the length of time a patient with cancer remains alive), lung function and disease recurrence. Patients were followed for a median of seven years.

After five years, patients who underwent surgery to remove part of their lung had similar rates of disease-free survival (63.6% versus 64.1%, respectively) and overall survival (80.3% versus 78.9%) compared with those who underwent surgery to remove a whole section of the lung.

Researchers also did not notice any significant differences between the two groups regarding the incidence of locoregional recurrence (recurrence of cancer in the same area as the original tumor or in nearby lymph nodes) or distant recurrence (cancer that has returned in another part of the body far away from its original site).

At six months, patients who under- went surgery to remove part of their lung had improved predicted forced expiratory volume in one second (the volume of air that a patient exhales during a forced breath during a certain period of time) compared with those who had an entire lung removed, although the difference between both groups was just 2 percentage points.

Altorki explained that the area of surgical treatment for stage 1A NSCLC has improved drastically over the past 15 to 20 years. Approximately 80% of
the procedures to remove a lobe of the lung or less than a lobe now are done minimally invasively, which he called “an amazing change in how we practice.” 

He also said that the mortality risk from surgery or during hospitalization is an estimated 1% when the entire lobe is removed and approximately 0.5% for the removal of less than a lobe.

“It’s slightly lower, it’s not significantly lower, but it’s important,” Altorki said. “If you can halve the death rate, that would be great.”

Because the findings from this study confirmed success in removing less than a lobe of the lung in appropriately selected patients with stage 1A NSCLC, Altorki said that the implementation of this surgical tactic may be an easy transition in the operating room.

Altorki said, “I think people were already thinking (that removing less of the lobe would result in similar outcomes) before the trial, and the trial sort of gave them the ‘Yes, you’re right, you could do that. It’s OK.’ And it is good for patients. If there’s any winner in this, it is the patient who won, because you don’t want any more of your body (removed than you) need to.”

For some patients with non-small cell lung cancer, removing part of the lobe rather than the entire lobe still provides benefit, study results show.

Doing More With Less in Lung Cancer Surgery

For years, options for people living with non-small cell lung cancer (NSCLC) were limited, says Dr. Jamie Chaft, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.

But as cancer therapies advance, treatments that were once out of reach for many patients with NSCLC have become available. A therapy that began its history as a last resort has slowly made its way into frontline settings, and researchers continue to discover novel treatments.

And each new discovery saves lives. One example of progress in lung cancer is the Food and Drug Administration’s (FDA’s) January approval of 

Keytruda (pembrolizumab) for patients with stage 1B, 2 or 3A NSCLC

 following resection and platinum-based chemotherapy. Keytruda is an immunotherapy drug that has been approved for a variety of cancers, including advanced (metastatic) lung cancer, but was only recently approved as a post-surgery, or adjuvant, therapy for patients with early-stage NSCLC who have also been treated with chemotherapy.

“This is clearly a very busy space,” Chaft says of NSCLC research. “Postoperative and preoperative spaces were stagnant for decades. And then, in the last 3 years, we’ve now seen some advances, (and) we can bring therapies proven to be beneficial for patients with metastatic cancer into the earlier stage.”

Mechanism of Action and Indications for Keytruda

Like all immunotherapies, Keytruda harnesses the power of the body’s natural immunity to kill cancer. Keytruda is a PD-1 inhibitor, meaning it blocks the production of a cell protein called PD-L1, which is involved in the proliferation of tumor cells and evasion of natural tumor immunity. By blocking PD-1, Keytruda allows the body’s immune system to attack tumors.

“(Keytruda) goes back about eight years at this point in terms of lung cancer,” explains Dr. Dwight H. Owen, a medical oncologist at The Ohio State University Comprehensive Cancer Center-The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus. “At least for (NSCLC), the first approvals were only for stage 4 or metastatic disease — and only after previous treatment with chemotherapy.”

Although initial studies earned the drug approvals for use in patients with tumors expressing high levels of PD-L1, further research found that the drug could benefit patients with NSCLC regardless of their PD-L1 status.
This makes Keytruda the second immunotherapy to be approved as a post-surgical treatment in patients with earlier-stage NSCLC. The first, 

Tecentriq (atezolizumab), was approved in 2021

, but that indication only applied to patients with PD-1 expression. One striking thing about Keytruda is that although it is a PD-L1 inhibitor, patients can receive — and benefit — from Keytruda regardless of their PD-L1 expression levels.

“The way that immunotherapy works is, it tries to reorient our own immune system to attack the cancer cells,” Owen explains. “In theory, our immune system should recognize cancer cells as bad actors. They’re not behaving the way that they’re supposed to; they’re growing when they’re not supposed to. So they should be recognized by the immune system, which should attack and
kill them. Some cancers develop a camouflage to protect cancer cells from the immune system. And what these immune drugs do is essentially remove the camouflage, allowing the immune system to recognize, engage, destroy and then remember what those cancer cells look like to go on and destroy other cancer cells.”

What makes the use of immunotherapy important in patients with early-stage NSCLC is that early treatment offers the best chance of a cure.

“Over the last few decades, we’ve realized that surgery alone is curative for some patients with early-stage lung cancer but not nearly as many as we hope,” Owen says. “The reason for that is almost certainly because there is still ‘microscopic’ or ‘micrometastatic’ disease left behind.”

This is when the use of adjuvant therapies that get rid of any remaining tumor cells becomes crucial.

“Taking what we know from metastatic disease from patients who get treated with immunotherapy, we know that when immunotherapy works, it works even better than chemotherapy,” Owen says. “And that’s why we’ve been very excited to see immunotherapy come in earlier into the disease to be able to cure more patients.”

The FDA based its approval of Keytruda for use in early-stage NSCLC on findings from the KEYNOTE-091 trial, which included 1,177 patients with completely resected lung cancer with disease stages ranging from stage 1B to 3A. Investigators in the phase 3 study randomly assigned patients to receive either 200 milligrams of Keytruda or placebo by IV once every 3 weeks for as many as 18 cycles. Most patients (86%) also received platinum-based chemotherapy after their surgeries.

Investigators reported that patients assigned to Keytruda had a median disease-free survival that was nearly a year longer than that of patients assigned to placebo: 53.6 months in the Keytruda group compared with 42 months in the placebo group. This means that patients assigned to take Keytruda after surgery and platinum-based chemotherapy were disease free for 11.2 months longer than those who received placebo following surgery and chemotherapy.

Dr. Michael Rotkowitz, a medical oncologist with Jefferson Health in Sewell and Cherry Hill, New Jersey, notes that the drug’s improvement in disease-free survival is particularly important.

“What we know historically is that for stage 2, 3A and even stage 1, the recurrence risks after surgery are over 50%,” Rotkowitz says. “The KEYNOTE-091 trial shows a reduction in recurrence risk — a marked disease-free survival benefit. I think this will be practice changing.”

Although a small minority of patients included in the study did not undergo platinum-based chemotherapy, those who did receive chemotherapy appeared to fare significantly better than those who did not.

Using both chemotherapy and immunotherapy appeared especially effective. In KEYNOTE-091, the median length of disease-free survival for patients who underwent platinum-based chemotherapy and were assigned to Keytruda was reported at 58.7 months compared with 34.9 months among patients who underwent chemotherapy but were assigned to placebo.

There were some limitations in the KEYNOTE-091 study. For one, experts were quick to point out that because it was designed several years ago, it makes use of a cancer staging system that is now out of date. By the current staging system, patients in the KEYNOTE trials would all be considered to have disease in stages 2 to 3.

Additionally, one subgroup of patients expected to benefit most from the therapy did not. “The (Keytruda) data showed improvement of disease-free survival irrespective of PD-L1 expression,” says Chaft. “Though oddly, it showed that patients with tumors that did not highly express PD-L1 did not benefit as much.”

Chaft added that she suspects this data point was a statistical anomaly rather than an indication of the drug’s true therapeutic benefit in this subset of patients.

Patients should be aware that Keytruda does come with side effects, although oncologists consider the drug to generally be well tolerated. Most commonly, patients taking Keytruda by itself have experienced nausea, fatigue, muscle and joint pain, rash, constipation, diarrhea, itching, decreases in appetite, fever, coughing and hypothyroidism, a condition in which the thyroid gland produces lower quantities of thyroid hormone than it should.

“The caveat is that anytime you escalate treatment, you are increasing the risk of side effects,” Owen says.

In the KEYNOTE-091 trial, hypothyroidism reportedly occurred in 22% of patients, whereas hyperthyroidism, or an overactive thyroid gland, occurred in 11%. Furthermore, 7% of patients reportedly experienced more severe organ inflammation including pneumonitis, or inflammation of lung tissue. Two patients in the study died of myocarditis (inflammation of the heart).

n general, Chaft says immunotherapies are very well tolerated but says that doctors considering Keytruda for patients with early-stage NSCLC should do so on a case-by-case basis.

“We certainly don’t want to harm patients by trying to increase their chances of a cure,” she explains. “Many of these patients are cured already, either by the surgery or the chemotherapy. Looking at the patient as a whole, what is their likelihood to benefit from the immunotherapy versus harm?”

Chaft and Owen also point out that people with certain genetic alterations, such as those with EGFR and ALK tumor aberrations, are more likely to benefit from treatments targeting those mutations rather than Keytruda.

“If their tumors are driven by one of these genetic alterations, they’re not likely to gain benefit (from Keytruda) and would be more appropriately directed toward a targeted therapy,” says Chaft.

Another important factor for doctors considering Keytruda in this setting is whether the patients have any autoimmune diseases, Chaft notes. In this situation, she says, Keytruda should be avoided.

Unmet Needs and the Future of NSCLC Treatment

Cancer treatments continue to evolve, particularly in the area of immunotherapy. Rotkowitz pointed out that more and more often, patients receive chemoimmunotherapy before surgical resection, even as adjuvant therapies advance.

“There’s been a huge push toward chemo-immunotherapy before surgery, and those patients get chemotherapy with (the immuno- therapy drug) Opdivo (nivolumab),” he says. “On the other side, there’s been a huge emphasis on moving (therapies) to the front line.”

“Considering preoperative chemoimmunotherapy really may be the way of the future,” she says.

Regulatory approval and the release of new data have already begun to reflect this trend. The FDA in March 2022 

approved Opdivo combined with platinum-doublet chemotherapy

 as a neoadjuvant (presurgical) treatment in early NSCLC.

Keytruda also recently made headlines for another NSCLC study, in which Keytruda plus chemotherapy followed by surgery and post-surgical treatment with Keytruda improved event-free survival (the time after treatment ends that a patient is free from complications or events that treatment aims to prevent
or delay) in patients with stage 2, 3A and 3B NSCLC.

Chaft notes that in the coming year, data from two additional studies of immune checkpoint inhibitors also will become available, adding to the growing body of evidence and treatment options for immunotherapy in lung cancer. 

Chaft was also an investigator on a recent study of adjuvant Opdivo.

Additional research is also being done in the metastatic setting, with immunotherapy as well novel targeted therapies, says Rotkowitz. Investigators are evaluating options like CAR-T (cell-based) therapy and anti-CLTA-4 (another immune checkpoint like PD-L1) agents.

“There’s a tremendous amount of research going on,” he says. “A tremendous amount of innovation.”

Feature

Treatment for patients with non-small cell lung cancer has evolved to include immunotherapy after surgery and chemotherapy.

CURE Lung Cancer Special Issue

Inflammatory Biomarkers From Lung Cancer, Depression May Predict Survival Outcomes

Taking Cancer Support to a New Level

Early Supportive Care Extends Life, Eases Cancer Symptoms

Doing More With Less in Lung Cancer Surgery

The Way of the Future for Treating Early-Stage NSCLC

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