®, has covered medical news for MJH Life Sciences, 

®’s parent company, since 2021. She has written for 

 and a variety of other lifestyle publications. She attended Emerson College, where she studied journalism and publishing. Antonia enjoys traveling, cooking, yoga and all things health and wellness. Follow her on Instagram @antonialdepace or email her at 

Antonia DePace

Tislelizumab plus chemotherapy demonstrated clinically meaningful improvements in progression-free survival (the amount of time that a patient lives with cancer without disease worsening after treatment) versus standard of care chemotherapy as a first-line treatment for patients with stage 3B or 4 advanced squamous non-small cell lung cancer (NSCLC).

Of note, tislelizumab is not approved by the Food and Drug Administration, but there are ongoing trials looking into this monoclonal antibody checkpoint inhibitor.

According to Dr. Jorge J. Nieva, a medical oncologist and section head of solid tumors at USC Norris Comprehensive Cancer Center in Los Angeles, while the data presented don’t necessarily show anything new, these results foreshadow innovations like lower drug prices, which will benefit patients with lung cancer worldwide who may not have been able to afford the treatment otherwise.

“The development of these Chinese drugs is going to drive two things. It’s going to drive lower prices and it’s going to drive innovation,” he explained in an interview with CURE®. “It’s going to be easier for these Chinese firms to replicate Western clinical trial results with new antibodies. From my standpoint, these antibodies are all more alike than they are different. While many of us prefer to drink Coca-Cola or Pepsi, generic colas taste pretty similar. That’s effectively what we have here. This is going to require the drug manufacturers in the U.S. and Europe to begin to develop more innovation. ... These changes are all good for patients.”

In the study, patients received one of the following combinations:

A treatment regimen of tislelizumab plus paclitaxel (group A).

Tislelizumab plus Abraxane (nab-paclitaxel) and carboplatin (group B).

Standard-of-care chemotherapy with paclitaxel plus carboplatin (group C).

Findings showed that progression- free survival was longer in the groups that received tislelizumab. Specifically, for those with stage 3B disease, the median progression-free survival for group A was 9.8 months versus 5.6 months in group C. The median progression-free survival in group B was 11 months.

For patients with stage 4 disease, the median progression-free survival in group A was 7.6 months versus 5.2 months in group C; the median progression-free survival was 7.4 months in group B.

In terms of overall response rate (the number of patients who see a partial or complete response to therapy), patients with stage 3B disease demonstrated an overall response rate of 84.2%, compared with 82.5% in group B and 59.1% in group C. For patients with stage 4 disease, group A showed an overall response rate of 67.1%, compared with 70.9% in group B and 44.2% in group C.

Nieva said the outcomes associated with tislelizumab are similar to those of a common checkpoint inhibitor.

“This is generic Keytruda, and (patients) don’t need to think about it as anything more than that,” he said. “It’s a similar strategy in terms of drug selection (and) effect size. It’s another study of chemotherapy in combination with a PD-1 checkpoint inhibitor. It shows that adding a checkpoint inhibitor to chemotherapy makes it work better, so there’s nothing new to learn here. ... All we learned is that it doesn’t matter who manufactures the antibody; you’ll get a similar effect. And so to that sense, the only thing the study told us is that maybe someday prices will come down.”

The most common side effects across all groups included anemia, hair loss, decreased white blood cell count and low neutrophil count.

“There (are) a lot for patients who have high PD-L1 scores. They can be treated with a checkpoint inhibitor alone, ... with a checkpoint inhibitor plus chemotherapy (or) ... two checkpoint inhibitors and chemotherapy. All of these are options. And they all represent overwhelming advance over how we treated lung cancer patients 10 years ago that no matter which particular strategy is selected by a patient and their doctor, they know that anything that involves these — I could say almost miraculous class of drugs — is going to be giving them an opportunity for cure,” Nieva said.

He also added that he hopes that studies like this will push researchers in the U.S. to discover more innovative treatments, including subcutaneous formulations (drugs given as an injection) instead of intravenous ones (drugs given through the veins). He also said that this could lead to newer checkpoint inhibitors that may generate similar responses.

“There are a number of exciting new checkpoints that are going to come out and understanding how to use those checkpoints in an additive fashion with the current standards of care is going to be important,” Nieva said. “We’re going to have additional science around delivering these drugs and new delivery methods. Are these drugs safe enough to administer at home and self-administer? That’s going to be something that could potentially become a wave of the future for the checkpoint inhibitors, because I do see the drugs as actually being quite safe. Other innovations are going to come from understanding why some people don’t respond and trying to fix that so that they do.”

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

Articles

Recent results may lead to more checkpoint inhibitor options and lower treatment prices, giving accessibility to more patients with lung cancer worldwide.

A ‘Miraculous Class of Drugs’ to Increase Accessibility in Lung Cancer

Jerry Sanford retired to Naples, Florida, after a 29-year career as a New York City firefighter, but the city managed to call him back to help his brothers right before one of the most critical times in the history of the United States: 9/11. Although Sanford later developed cancer potentially associated with the fumes and toxins surrounding Ground Zero, he felt it was important to recount his experiences from the weeks leading up to and following 9/11 in his book, “It Started With a Helmet: A Retired Firefighter’s Return to New York City the Day Before 9/11.”

Within the pages of the book, which was published soon before the 20th anniversary of the attacks, readers will also find stories about Sanford’s time as a New York City police officer before starting with the city’s fire department, as well as his own diagnosis of adenocarcinoma, a type of lung cancer found in the glandular cells in the organ’s tissues, which likely developed from his exposure to the toxic air.

“It’s an appropriate title because it all started in Naples, Florida. How did a helmet from New York City get from the Bronx to Naples, and from Naples back to the Bronx? The book is all about that,” Sanford said in an interview with CURE®. “It’s a very slim novel, but it categorizes a little bit of my life when I was a police officer,
my story about 9/11 and then what happened, what (I did) after 9/11.”

After what he describes as “driving his wife crazy” for five months, Sanford found himself at the North Naples Fire District station for an interview with the chief for a public information officer position.

Sanford shared a copy of his book with the firefighters of Ladder 131 in Red Hook, Brooklyn in August 2021.

About a month into the job, Sanford was presented with an old New York City firefighter helmet that had been dropped off at the station in Florida. “(The chief) said to me, ‘We have an old New York City fire helmet here that a man brought in. It was his father’s, and he didn’t want it anymore,’” Sanford explained. He called Ladder 42, the company the helmet came from. The station was undergoing a renovation, so it was decided that Sanford would return it when the work was done in 2001.

On September 11, 2001, Sanford was flying from New York City back home to Naples with his wife, Maria. A few days before, he had come to return the old helmet to Ladder 42, and participated in a rededication ceremony for it. But two hours before he flew out of LaGuardia Airport, the world changed. The two planes had crashed into the World Trade Center, releasing about 24,000 gallons of jet fuel, at least 100,000 tons of organic debris and 230,000 gallons of transformer, heating and diesel oils. It wasn’t until he was changing planes in Pittsburgh that he learned what was happening.

Jerry Sanford kept some of his credentials from working at the press office after 9/11. He also previously reunited with his first firehouse in Harlem.

“And at first, I didn’t comprehend. I thought it was a sightseeing plane or something. But then we got thrown off the plane and it was pandemonium in the airport. We then quickly tried to get a car and get out of Pittsburgh. And then we found out by listening to the radio that, in fact, the second plane had hit the second tower, (then) Shanksville and the Pentagon. So it (was) a very heavy day,” Sanford remembered.

Two weeks later, Sanford returned to Brooklyn to help. “And the job was just torn apart. We had lost so many men from so many different ranks,” he said.

Jerry Sanford reunited at the Prospect Avenue firehouse in the Bronx, which is home of Ladder 42/Engine 73, where the helmet is displayed.

Sanford was assigned to the press office, where he would handle the media and attend funerals of those rescue workers who had died in the chaos. He recalled: “I could go into the firehouse and cry and grieve, which I did with my brother firefighters, but the media ... you had to kind of keep them at bay because they were from all over the world. This was a worldwide story. It wasn’t just a New York City story.”

Sanford said he knew about half of the rescue workers who lost their lives that day.

“I thought, wait a minute, this can’t be New York City, this can’t be where I served for 30 years,” Sanford recalled. “And it was just a horrible experience seeing that, but you know what, you have to do it, you got to pull up your pants, you got to get out there and you have to do it. Because you know what? They would have done it for me. And that’s why I was there. Because the brothers, we don’t leave anybody behind. We get in there and as the thousands of people are exiting the World Trade Towers — we’re going in. I’m very proud of the role, my small role. Everybody played a role that day. Everybody has a story. But I’m very proud that I was able to come back to New York and help.”

After the towers fell, a giant, toxic cloud loomed over Ground Zero. For hours, days and weeks after, rescue workers — including Sanford — inhaled the fumes. Twenty years later, the impact of those fumes is still being felt. According to Cancer Treatment Centers of America, an estimated 2,000 responders and Ground Zero workers have died from diseases including prostate cancer, leukemia, thyroid cancer and lung cancer, possibly attributed to the fumes they inhaled on the site.

In addition, rescue workers who helped during the aftermath of 9/11 may have a 9% increased risk of receiving a cancer diagnosis.

In December 2007, Sanford was diagnosed with adenocarcinoma in his upper right lung. His oncologist at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, recommended a surgical approach. A recurrence in February 2008 of the same cancer in the lower left lung led to another successful surgery. “I went every year after that to my oncologist, and I had my CAT scan every year and everything was fine,” he explained.

But in 2012, the cancer returned. This time, his oncologist recommended extensive chemotherapy and radiation. “But God is good. I never got sick,” Sanford said.

Sanford has been cancer free since that year.

Twenty years ago, “we all came together as one neighborhood. Everybody was a New Yorker 20 years ago, helping everybody,” Sanford said. “But on the sad side, we keep losing firefighters and police officers every day from something that happened 20 years ago — from that cloud, that terrible cloud that we ingested, including myself. It took six years for (doctors) to detect it in me.”

to Jerry Sanford's full podcast episode here. 

Twenty years after 9/11, a retired firefighter reflects on the weeks following the attacks, as well as his own diagnosis of lung cancer six years later, in a newly published book.

9/11 Firefighters and Unending Tragedy: 'Together as One Neighborhood'

Despite a decrease in lung cancer rates across the country, significant differences in disease rates and outcomes remain at the state level because of a variety of disparities, according to study results presented at the annual meeting.

In the presentation, Dr. Raymond U. Osarogiagbon, a medical oncologist at the Baptist Cancer Center in Memphis, Tennessee, discussed the geographic disparities in lung cancer mortality rates across the United States.

“We know that (lung cancer) is the oncologic challenge of our age. If one takes the perspective of the sheer cost in terms of human life, (it is) the No. 1 killer of men and women in the United States and in a lot of countries around the world. ... In the United States, the good news is it has been going down sequentially over time,” Osarogiagbon explained in an interview with CURE®. “The bad news, though, is in the United States, if you dug in a little bit deeper, you will find a very different picture. At the state level, if we disaggregated lung cancer as a cause of death, you will find a huge difference between the states ... with the cluster of highest per capita death risk in the Southern and Midwestern United States.”

States with the worst lung cancer mortality rates include Kentucky, Mississippi, Arkansas, Tennessee, West Virginia, Alabama, North and South Carolina and Louisiana, according to Osarogiagbon.

“At the county level, the difference is even worse,” he said, noting that there are some that have rising numbers of death due to lung cancer such as the Appalachian Regional Authority and Delta Regional Authority, while others have plateaued with no decrease.

Disparities that come into play include women and racial minorities being at a higher risk for lung cancer despite lower levels of tobacco exposure.

Dr. Kim Lori Sandler, an associate professor of radiology and radiological sciences and co-director of the Vanderbilt Lung Screening Program at Vanderbilt University School of Medicine in Nashville, Tennessee, emphasized that there are exposures other than smoking that can contribute to disparities. “We know that smoking is the No. 1 cause of lung cancer, but there’s also other causes. We know radon exposure and other types of exposures can be a cause of lung cancer. Certain populations are continuing to have those exposures like smoking and other high-risk exposures,” she told CURE®.

This is where the importance of lung screenings comes in, said Sandler, who was not associated with the study presented at the meeting. “The populations that were highlighted in the presentation, a lot of it looks at this Southeast region where we continue to have very high rates of smoking,” she said. “And unfortunately, our rates of lung cancer screening (in that region) have remained lower than other areas of the country, like in the Northeast. If you look at maps of the availability of lung cancer screening programs, you see them very highly localized in these Northeast centers where there are a lot of different programs available, and then when you get to the Southeast, they’re more spread out and patients need to travel further in order to be able to enroll in those programs.”

According to Osarogiagbon’s presentation, keeping up with yearly lung cancer screenings, which are usually covered by insurance, would reduce the risk of dying from the disease by 20%.

“It is from the point of onset on, whether it is finding (lung cancer) early, whether it is receiving optimal treatment for it, whether it is receiving the proper surveillance for it after diagnosis and treatment ... there are highly preventable differences,” he said. “It is people who live in parts of the world, or parts of the country that have resources that are organized in a certain way, who do well and not others. It is White people who do well, better than racial minorities. It is oftentimes when we’re talking about interventions themselves and access to them, it is men who do better
than women. And these are all things that are all necessary — things that significantly inhibit the full benefits of discovered innovations.”

The lack of screenings taking place in those states with higher cases of death from the disease may also lead to later-stage diagnoses. In this circumstance, that means that not as many patients with lung cancer will be able to be cured with surgery. For example, 50% of patients with lung cancer in Wyoming can be cured by surgery versus 90% in states like New Jersey, Massachusetts and Utah.

“If you drill further down and go to the county level, it’s even uglier than that. There are counties at the low end as low as 12% of patients with early-stage lung cancer that can be cured by surgery,” Osarogiagbon added.

Of note, the five-year survival rate of an early-stage lung cancer diagnosis is 90%. But once the disease enters late-stage, the five-year survival rate drops to 10% or lower. “Ideally, when we detect lung cancer, we’d love to find it at its earliest stage where we could cure a patient with a minimally invasive surgery, not requiring chemo- therapy or radiation therapy,” Sandler explained. “In our screening program, it’s unusual to say finding cancer is a win. But if you can find it that early, and truly offer a curative option for the patient, that’s an enormous victory for us.”

These disparities must be confronted with a multipronged approach, according to Osarogiagbon.

“We (need to) begin to focus on preventing, narrowing (and) eliminating disparities. We have to understand that the solutions come from multiple levels. The least effective is the level of directly hectoring, nagging (and) blaming the victims of disparities. (Patients) don’t go in with the idea that they will do something to hurt themselves. A (patient with) lung cancer who is poor does not stand up in the morning and decide, ‘Yippee, I am going to make sure I get the wrong treatment today. I don’t care if I die.’” he said. “When we talk about disparities, it is very important for (providers) to get away from the traditional, narrow lens of who are these people or why do they have such terrible outcomes, and recognize that we have seen the enemy. It is us.”

Sandler agreed with the outlook, emphasizing the need to banish the stigma around smoking and lung cancer, especially when other factors could be at play.

Because of this, Sandler believes that further investigation on eligibility for screenings and expanding eligibility to at-risk populations would make an impact, along with engaging further with communities to enhance outreach and education.

She noted that there have been some steps forward. “In terms of the disparities, the guidelines were just updated earlier this year, and they did decrease the age to 50 (and the pack-year smoking history) to 20, from 55 and 30, respectively,” she said. “And if you look at the recommendations from the (United States Preventive Services Task Force), they specifically say that this is to address disparities in the African American community and for women, because those are the populations that we’re really going to see an increase in eligibility. It’s not perfect. It’s a first step. But I think having that conversation and seeing the readiness of different organizations to accept new guidelines and continue to work on new guidelines is a really, really positive step forward.”

Looking deeper into mortality rates highlights the importance of eliminating disparities in lung cancer and expanding screening eligibility for at-risk populations.

Facing Disparities in Lung Cancer Mortality Rates

Recent drug approvals by the Food and Drug Administration (FDA) are giving patients with non-small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations the first two treatments that specifically target those mutations.

“EGFR is one of the classic driver mutations,” Dr. Catherine Ann Shu, clinical director of the thoracic medical oncology service at Columbia University Irving Medical Center in New York, explained in an interview with CURE®. “When patients hear about having an EGFR mutation, it’s typically associated with drugs like osimertinib (Tagrisso) or lorlatinib (Lorbrena) ... and those patients tend to do very well on those treatments with a very high response rate. ... But unfortunately, there is another type of EGFR mutation. Most people aren’t really aware of it, but it’s called exon 20 insertion. And patients with those EGFR exon 20 insertions generally do not respond to the classic drugs.”

EGFR mutations exist within 85% of lung cancer cases. Of those, about 10% are exon 20 insertions. “Because it’s more rare, it hasn’t been something that’s been explored as much,” Shu said. “And it is more heterogeneous than the other EGFR mutations. The other EGFR mutations tend to be exon 19 deletions and L858R, which is a pretty standard thing. And exon 20 insertions can be a whole variety of insertions or duplications, so they don’t all look exactly the same. Sometimes it’s a little bit harder for patients and providers to know exactly what’s going on.”

Dr. Pasi A. Jänne, a translational thoracic medical oncologist at Dana-Farber Cancer Institute in Boston and a professor of medicine at Harvard Medical School, noted that it’s easiest to think of exon 20 as a collection of mutations that occur within a particular part of the exon 20 part of the gene. He also said there are data that suggest the mutation is more common in those of Asian descent, likely due to a genetic contribution that hasn’t been thoroughly researched.

For patients with lung cancer and an EGFR exon 20 mutation, the standard of care has been chemotherapy, according to Jänne. “Until recently, all of the therapies that have been approved for the more common types of EGFR mutations have not been effective in this subset of lung cancer; hence, there’s been a great interest in trying to develop specific therapies that would be effectivein the EGFR exon 20 subset of lung cancer,” he added.

The emphasis being on “until recently,” Jänne noted that the FDA approved Rybrevant (amivantamabvmjw) as the first targeted therapy for the patient subset in May 2021. In the study that led to the approval, 81 patients with NSCLC and an EGFR exon 20 insertion mutation whose disease had progressed after platinum-based chemotherapy participated. After treatment with Rybrevant, patients had an overall response rate (patients who had a complete

or partial response to the therapy) of 40%. There was also a median duration of response (the time that a tumor responds to treatment without growth or spread) of 11.1 months in all patients, while 63% of the patients experienced a response to the therapy for at least six months.

“The response is higher than probably just chemotherapy would be, but remember that these response rates are in patients who have had chemotherapy,” explained Shu, who was the lead author on the study that led to the drug's approval. “This is post- platinum chemotherapy.

Generally, we see a decrease in response rate with every line of therapy. If you think about it, this 40% is already after they’ve progressed on chemo, so it’s really quite good.”

Common side effects from the drug included rash, skin infections around the fingernails or toenails, nausea, fatigue, sores in the mouth, cough, constipation and vomiting. Shu added that there’s also an infusion-related reaction that typically presents on the first dose as shortness of breath, flushing or nausea. It can be managed by lowering the dose and prescribing pre-medications.

One factor to be aware of, according to Shu, is the scheduling around the drug, which is an IV infusion. “The schedule is a little bit more of a pain than being on a pill,” she said. “You have to go in for infusion, (and) the first infusion is split up over two days.

You have to go on day one and on day two because we try to do it slowly to prevent that infusion-related reaction, then you have to come in again on day eight, which is the following week. You have to come in again on day 15.

It’s weekly for the first few weeks, and then it goes out to every other week. It is a little bit more time intensive than even some chemotherapies, but if you can see past that ... the pros definitely outweigh the cons.”

After the FDA’s first targeted therapy approval for this patient subset, the dominoes quickly fell into a second one. In September 2021, Exkivity (mobocertinib) was approved for the treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression after receiving platinum-based chemotherapy.

Within this study, researchers observed an overall response rate of 28% and a median duration of response of 17.5 months. The median overall survival (the time from treatment that a patient with cancer is still alive) was 24 months, while the progression-free survival (amount of time during and after treatment that a patient lives with cancer without it progressing) was 7.3 months.

“For (Exkivity), the side effect profile is a little bit different (compared with Rybrevant). It’s more gastrointestinal (GI) side effects. There’s more of a diarrhea type of side effect, there is some skin rash, but it’s not as predominant as the GI side effect can be. They’re sort of two different classes: skin side effects and GI side effects. And both, with appropriate management and dose reductions, can be manageable,” explained Jänne, who was the lead author on the study that led to the drug's approval.

More specifically, common side effects included diarrhea, rash, nausea, stomatitis (inflamed and sore mouth), vomiting, decreased appetite, paronychia (infection surrounding the fingernail), fatigue, dry skin and musculoskeletal pain.

According to Jänne, next steps for further investigating therapies for this patient subset include looking at the newly approved drugs as monotherapies or combination therapies. “There are clinical trials to see whether — in combination with chemotherapy — (Rybrevant) would be better than chemotherapy as initial therapy. And as a single agent, whether (Exkivity) would be better than chemotherapy as initial therapy for this subset of individuals,” he said. “The paradigm is typically that you get an approval in a following treatment with prior standard of care. And then the next question is: Is this an agent to replace or add to the standard of care? But it’s exciting to have these options for individuals. We didn’t have these several months ago, and we hope that (these two approvals are the first of) many to come.”

Two new FDA approvals for patients with lung cancer and EGFR exon 20 insertion mutations have given the subset its first targeted therapies.

Antonia DePace

A ‘Miraculous Class of Drugs’ to Increase Accessibility in Lung Cancer

9/11 Firefighters and Unending Tragedy: 'Together as One Neighborhood'

Facing Disparities in Lung Cancer Mortality Rates

The First of Many Advancements to Come for a Lung Cancer Mutation

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