How a Targeted Drug Developed for Breast Cancer Is Helping People with Lung Cancer

A photo of Paula with her dog; Paula in a graduation cap and gown; Paula at a pottery wheel; and Paula snowboarding.

(Clockwise from left) Paula Freitas and her therapy dog, Fogo, in December 2020; Paula at her graduation from the Nurse Anesthesia program at SUNY Downstate in 2013; Paula at her pottery wheel in the mid-1990s; Paula snowboarding in 2003. Photos courtesy of Paula Freitas

Paula Freitas has had many callings in her life: mother, anesthesia nurse, world traveler, ceramics artist, extreme sports enthusiast, and professional skydiver. Unfortunately, for the past two years, she’s had a role she never wanted: a person with stage 4 lung cancer.

But now she’s also playing an important part in a clinical trial testing a new treatment for lung cancer, using a drug originally developed for breast cancer.

“When I found out about this trial, my MSK oncologist, Jamie Chaft, told me this was a great opportunity,” says Paula, 58, who lives in New York. “I asked her if she would advise a member of her own family to enroll in the trial, and she said, ‘Yes.’ So I jumped on it.”

The drug — called trastuzumab deruxtecan (also known as T-DXd or Enhertu®) — targets a protein called HER2, most often found in breast cancer. HER2 mutations in lung cancer are more commonly found in younger people, women, and nonsmokers like Paula, although experts aren’t sure why.

Delivering a Toxic Payload to Tumors

Paula is enrolled in a phase II clinical trial led by MSK thoracic oncologist Bob Li, who presented results at the European Society for Medical Oncology annual meeting September 18, 2021. The study, which also was published in the New England Journal of Medicine, found that among 91 patients who were enrolled in the study, more than half (54.9%) responded to the drug, which means that their tumors got substantially smaller. In 84 patients (92.3%), T-DXd produced disease control.

Trastuzumab deruxtecan works like a targeted missile, delivering a toxic payload right to tumors.

The average duration of that response was just over nine months, and the average survival time was almost 18 months — with some patients continuing to respond quite well beyond that time. “For a patient population in which standard treatments have failed, this is a significant advancement,” Dr. Li says.

The drug works like a “targeted missile,” he explains. It’s made up of two parts: an antibody called trastuzumab that’s linked to eight molecules of a type of chemotherapy called deruxtecan, a topoisomerase 1 inhibitor. The antibody homes in on the abnormal HER2 protein, which is found on cancer cells, and delivers its toxic payload right to the tumors.

T-DXd was originally developed for breast cancer. MSK breast medical oncologist Shanu Modi oversaw much of the research that led to its approval for breast cancer by the US Food and Drug Administration in December 2019. T-DXd is also approved for people with advanced stomach (gastric) cancer that’s caused by an excessive amount of HER2 protein.

But lung cancer caused by HER2 is different from some other cancers caused by this protein. In breast and stomach cancers, cancer cells make too much HER2 protein (called overexpression), which drives the growth of cancer cells. But in lung cancer, in addition to overexpression, the tumors may also have mutations in the HER2 gene. The mutations can cause the production of a faulty HER2 protein, which makes the cancer grow.

Dr. Li has studied the connection between HER2 mutations and cancer for many years. A phase I trial, which he published in March 2020, found that T-DXd is also effective against colorectal, biliary tract, uterine (endometrial), and salivary gland cancers with either HER2 overexpression or a HER2 mutation. Another of Dr. Li’s papers explained how two-part, HER2-targeted drugs like T-DXd work on a molecular and cellular level.

Molecular Testing Guided Paula’s Treatment

When Paula was diagnosed with cancer in 2019, she was already very familiar with MSK — she worked there as a certified registered nurse anesthetist. When she began to feel pain in her hip, she initially chalked it up to her active lifestyle, although she didn’t remember any injury. After an x-ray didn’t find anything out of the ordinary and physical therapy failed to provide relief, Paula insisted on an MRI. By that point, the pain was so bad she had difficulty walking.

When the MRI revealed a tumor on her hip, Paula immediately went to see MSK orthopedic surgeon Nicola Fabbri, with whom she frequently worked in the operating room. Dr. Fabbri performed a biopsy and learned that Paula did not have a sarcoma, as originally suspected. Instead, a non-small cell lung cancer had spread to her hip. A CT scan later revealed that the cancer had also spread to her brain. The news was devastating.

Maintaining the function of her hip was important to Paula, so her first treatment was radiation therapy to shrink that tumor. She also had radiation to shrink the tumors in her brain. Dr. Fabbri then performed hip replacement surgery. Once she had recovered, Paula began chemotherapy with Dr. Chaft.

“Paula responded well to the chemotherapy for a while, but not for long,” Dr. Chaft says. “This is not uncommon in the first line treatment of lung cancer.”

But MSK has a groundbreaking test to help identify cancer cells that don’t respond to more-traditional treatments. When she was first diagnosed, Paula’s tumor was analyzed with MSK-IMPACTTM, which looks for mutations driving tumor growth that can be targeted with drugs. That test revealed that her cancer had a mutation in the HER2 gene, which produced a faulty protein and fueled its growth. Those results made her a candidate for Dr. Li’s trial. She began receiving T-DXd in June 2020.

Thanks to MSK-IMPACTTM, a groundbreaking test to help identify cancer cells that don’t respond to more-traditional treatments, doctors learned that Paula’s cancer had a mutation in the HER2 gene.

A Targeted Treatment with Fewer Side Effects

Because the therapy is designed to affect cells with elevated or abnormal HER2, it has fewer side effects than regular chemotherapy. Paula has experienced some nausea, but most of her side effects, including pain and tingling in her feet, are likely from her earlier chemotherapy, Dr. Chaft says. In Dr. Li’s trial, the most common side effect was low white blood cell counts. A small number of patients experienced a potentially fatal condition called interstitial lung disease, and two died from it. This side effect was known from the earlier trials for breast cancer and stomach cancer, and it’s something for which patients in the trial receive regular monitoring, guided by Elizabeth Panora, an MSK clinical trials nurse who works in thoracic cancers.

Only about 2 to 4% of non-small cell lung cancers carry a HER2 mutation, but because lung cancer is so common, thousands of patients could benefit from this drug every year.

During the COVID-19 pandemic, Paula has been living in upstate New York, where she’s working on her pottery and taking lots of hikes. She comes to the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center every three weeks to see Dr. Chaft and receive her T-DXd, which is given as an infusion. “The treatment is very quick compared to chemo — it only takes about half an hour,” Paula says. “I’m very grateful for the chance to participate in this trial and for my wonderful care team.”

This role is not one Paula sought out, but she says she’s pleased to play a part in finding a new therapy for thousands of patients like her.


Key Takeaways
  • Trastuzumab deruxtecan, a drug that was originally developed to treat breast cancer, is also effective against some lung cancers, a new study shows.
  • The drug consists of two parts: an antibody that seeks out a protein called HER2 and that’s linked to chemotherapy molecules that it delivers right to the tumor.
  • Paula Freitas, a certified registered nurse anesthetist at MSK, has been receiving the drug for more than a year.
  • MSK medical oncologist Bob Li recently published results from a clinical trial that found the drug shrinks tumors in more than half of people with advanced lung cancer driven by HER2.

This trial was funded by Daiichi Sankyo and AstraZeneca. 

Dr. Li is supported by Research Project Grant R01CA249666 from the National Institutes of Health. He has served as an uncompensated advisor and consultant to Daiichi Sankyo, AstraZeneca, Amgen, Genentech, Boehringer Ingelheim, Lilly. He has received research grants to his institution from Daiichi Sankyo, AstraZeneca, Amgen, Genentech, Lilly, Illumina, GRAIL, Guardant Health, Hengrui USA, MORE Health and Bolt Biotherapeutics. He has received academic travel support from MORE Health and Jiangsu Hengrui Medicine. He is an inventor on two institutional patents at MSK (US62/685,057, US62/514,661) and has intellectual property rights as a book author at Karger Publishers and Shanghai Jiao Tong University Press. Dr. Chaft has relationships with and/or financial interests in AstraZeneca; Clinical Care Options; Flame Biosciences, Inc.; Genentech; Imedex, Inc.; MJH Associates; Merck KGaA; Novartis; OncLive; PeerView Institute for Medical Education (PVI); Physicians’ Education Resource; Practice Point Communications, LLC; Shanghai JoAnn Medical Technology Co., Ltd; and i3 Health. Dr. Fabbri has relationships with and/or financial interests in Illuminoss, Onkos Surgical, Smith & Nephew, and Springer Publisher.