Dermatologic Manifestations of Paraneoplastic Syndromes

FDA Approves Drug For Aggressive Small-Cell Lung Cancer

The FDA has approved the drug durvalumab for adults with limited-stage small-cell lung cancer (LS-SCLC) whose disease hasn't gotten worse after getting platinum-based chemo and radiation at the same time.

LS-SCLC is an aggressive form of small-cell lung cancer that starts in the main airways of the lungs (bronchi) and is generally limited to one lung or one side of the chest. The LS-SCLC cells carry special proteins (PD-L1), which allow them to hide from the immune system, promoting their growth and spread. Often, despite early success with standard chemotherapy and radiotherapy, LS-SCLC often comes back with only about 15% to 30% of people surviving five years after diagnosis. This highlights the need for treatments that can target PD-L1 proteins to improve life expectancy.

Durvalumab, marketed under the brand name Imfinzi, is a human monoclonal antibody, a type of drug that uses your body's immune system to fight cancer. It binds to the PD-L1 protein and prevents tumor cells from evading the immune system, helping it to find and attack cancer cells more effectively.

Imfinzi was first approved by the FDA in 2017 for use against various lung and liver cancers, either alone or along with other treatments. Imfinzi is now the first and only immunotherapy approved for treatment in patients with LS-SCLC, according to a news release from AstraZeneca, the drug's maker. 

The effectiveness of Imfinzi was studied in a clinical trial done at 164 centers across 19 countries in North and South America, Europe, and Asia. It included 730 patients with LS-SCLC whose cancer had not worsened after platinum-based chemotherapy and radiation therapy. Patients were randomly selected to receive either Imfinzi alone, Imfinzi along with Imjudo (tremelimumab), or a placebo.

The results showed that the patients on Imfinzi lived longer (nearly 56 months, on average) than those receiving a placebo (33.4 months). Imfinzi also delayed the cancer's progression. The average time before the disease worsened was 16.6 months for those on Imfinzi, compared to 9.2 months for the ones receiving a placebo. The most common side effects were inflamed lungs and tiredness. The treatment's safety profile was the same as seen in previous trials, with no new safety concerns.

This Remarkable MSK Patient Is Living With Two Kinds Of Stage 4 Cancer

To see Michael Simien darting in and out of New York City streets on his bike, you'd never guess he is 70 years old — let alone that he is living with two kinds of metastatic cancer: lung cancer that was diagnosed 10 years ago and a rare, aggressive type of non-Hodgkin lymphoma called mantle cell lymphoma that was diagnosed five years ago.

Michael is keenly aware that he has beaten the odds. When a persistent cough led him to the emergency room of another hospital, a physician told him in the waiting room his scans suggested he had lung cancer. "There goes a bone fide walking dead man," he heard another patient say as Michael left the ER, stunned.

Michael wept and prayed, and then he got to work. His research led him to Memorial Sloan Kettering Cancer Center (MSK) for treatment, where he met with thoracic medical oncologist Helena Yu, MD. The cancer was inoperable, so Dr. Yu prescribed him chemotherapy for eight months. The side effects were rough.

"It hit me hard," remembers Michael. "My hands and feet darkened. I kept comparing myself to a burnt match, trying to keep a sense of humor about this."

Dr. Gilles Salles, Chief of MSK's Lymphoma Service, found a drug to control Michael's cancer.

The next course of treatment was much easier: an immunotherapy called nivolumab, infused every two weeks. The tumors started shrinking, and in September 2019, Michael rang the remission bell to celebrate his last treatment.

"It felt great," remembers Michael. "I was walking up out of the valley of the shadow of death."

Life was good again. Michael was able to work odd jobs, after years as a New York City corrections officer and bus operator. He relished spending time with his sister and his son, Michael Jr., whom he calls "Slim."

A Shocking Second Diagnosis: Stage 4 Mantle Cell Lymphoma

Seven months after he thought he was done with cancer, Michael was shaving and noticed swelling near his left ear and a lump in the back of his throat. A biopsy at MSK revealed stage 4 mantle cell lymphoma. He couldn't believe it. How could he have a second cancer diagnosed at stage 4? 

"This is it for me. I was thinking about where I was going to be buried," says Michael. "I really felt like giving up."

His MSK care team told him the two cancers were unrelated. They were just bad luck. But there was hope: MSK's unique diagnostic test, MSK-IMPACT®, found his cancer was caused by a mutation of the gene called TP53. It was a rare subtype of a rare kind of lymphoma. Then came the good luck: MSK's Chief of Lymphoma Service, Gilles Salles, MD, PhD, informed Michael that he qualified for an MSK clinical trial that was testing a combination of drugs including ibrutinib.

Since the clinical trial ended in July 2024, Michael has been taking a similar drug (zanubrutinib) that's keeping his cancer at bay with fewer side effects.

Full Speed Ahead

Michael Simien with his son, Michael Jr.

Now Michael is doing remarkably well. His cancer is not detectable and considered "dormant." Dr. Salles sees him at quarterly checkups, with scans every six months. He takes two zanubrutinib pills twice a day, and they're covered by Medicare. When Michael faced other financial challenges, such as covering his rent, the team at MSK patient financial services helped him apply for a grant to help pay for necessities.

Michael tries to spread hope whenever he can. He took the dire words he heard 10 years ago in the ER and turned them into the name of his poetry blog, "Walking Dead Man."

"People are coming to MSK thinking they are on their last legs," says Michael. "I remember talking to a patient one day, and I ended up reciting one of my poems. I had a little audience, and they all clapped. "

Michael says he's able to bike full speed ahead in life, thanks to the care he's received at MSK and his positive outlook.

"It took years," he says. "I used to think because of cancer I might not see this or I might not see that. But now I know it doesn't matter. Because I'm here now. "

'It's Not A Death Sentence': How Mum Of Two Overcomes Stage 4 Lung Cancer And Finds Calling In Comforting Others

Eight years ago, Ms Lee Hong Eng, then 38, battled a persistent cough for three months. Then she developed shortness of breath and an unexplained pain in her right shoulder.

An X-ray at a polyclinic revealed shadows in her lungs, and she was immediately transferred to the hospital, where she would spend almost three months under supervised medical care.

Further tests revealed she had fluid in her lungs that was pressing against her shoulder. This was her body's reaction to the cancer cells, which had spread from her right lung, where the tumour originated, to her left lung, affecting her spine and lymph nodes.

"I couldn't walk for more than 50m without feeling breathless," recounts Ms Lee, now 46, who did not expect her initial symptoms to lead to a life-changing diagnosis.

According to the 2022 Singapore Cancer Registry, lung cancer has one of the lowest five-year survival rates in both males (21.9 per cent) and females (37.8 per cent). It is also often diagnosed only in the advanced stage.

Dr Teh Yi Lin, a consultant at the Division of Medical Oncology at the National Cancer Centre Singapore, explains that the cancer's poor outcomes are largely due to its silent progression in its early stages1.

She adds: "The growth of lung cancer may not cause any obvious swelling, discomfort or breathlessness at first, and symptoms become more apparent once it has started to grow and spread to other areas."

With Ms Lee's lung cancer at stage 4 – the most advanced stage – the mother of two knew she faced significant challenges ahead. Her daughters were only in primary school then.

She recalls: "After the initial shock and tears, I knew I had to fight the cancer. I could not let myself be taken away from my girls."

Today, Ms Lee's cancer is in remission – her journey shows how advances in treatment and comprehensive care are helping more lung cancer patients live fuller lives.

Navigating lung cancer treatment

During Ms Lee's hospital stay in 2016, doctors arranged for a biopsy, followed by genetic testing on a cancer-stricken lymph node to check for mutations causing non-small cell lung cancer (NSCLC).

The test revealed that Ms Lee has the c-ros oncogene 1 rearranged NSCLC mutation, or ROS-1.

Dr Teh explains: "In general, NSCLC with gene mutations are more common in non-smokers and younger people."

In Western and Asian populations, she adds, ROS-1 rearranged NSCLC is among the rarer mutations often found in females and non-smokers like Ms Lee. A similar rare mutation is the Anaplastic Lymphoma Kinase (ALK).

"Depending on the type of lung cancer and stage of disease, patients may need to undergo surgery, chemotherapy, radiotherapy and targeted therapy or a combination of treatments," says Dr Teh.

"Advanced-stage lung cancer is incurable, and treatments are used to limit the spread of the disease, manage symptoms and prolong life."

Ms Lee (top right) has her cancer in control through a new long-term targeted medicine, allowing her to lead an active, fulfilling life with her family.PHOTO: COURTESY OF MS LEE HONG ENG

These treatments are also tailored to a patient's medical fitness and response to the treatments.

In Ms Lee's case, she began with a cycle of chemotherapy every three weeks for about 1.5 years. She was then switched to a ROS-1 targeted therapy treatment for another 18 months, which helped to shrink the cancer.

However, during a routine magnetic resonance imaging (MRI) scan, doctors discovered that the cancer had spread to Ms Lee's brain, resulting in 11 lesions. This is a common progression in lung cancer patients, Dr Teh notes.

As such, Ms Lee had to endure a brief but intensive course of gamma knife radiotherapy – her head fixed in place for hours during treatment.

She was then put on a new type of long-term targeted medicine, which has helped to control the cancer to date. She experiences side effects such as slurred speech, brain fog, hand numbness and constipation, which she manages through medication adjustments, diet and exercise.

While the journey has been challenging, Ms Lee has found strength in support groups, and has even gone further by helping cancer patients like herself.

A support network for lung cancer patients, caregivers and survivors

Led by Dr Teh since 2019, Lung Cancer Education and Advocacy for Patients (Leap) has helped over 600 lung cancer patients with comprehensive services – from coordinating medical appointments and treatments to financial assistance and emotional guidance.

"Each patient's journey is unique," says Dr Teh. "Through Leap, we've created a space where patients, families and survivors can connect and support one another while learning about the latest developments in lung cancer care."

Initially a beneficiary, Ms Lee received valuable assistance through patient navigators who helped her manage hospital appointments and access various support services. Today, she serves as a Leap patient advocate, working to improve cancer care services for fellow patients.

"I want to share my journey and show them there's hope," says Ms Lee. "I understand that when patients are first diagnosed, it feels like a death sentence. But it's not."

As part of the Leap community, she also facilitates and participates in its monthly activities, which range from educational talks to exercise sessions, art therapy and coffee appreciation. These activities create informal opportunities for the lung cancer community to connect and seek emotional support.

For Lung Cancer Awareness Month, Leap held its recent Resilience in Bloom event on Nov 2, 2024. Around 60 patients and caregivers attended to share their experiences.

Despite her cancer journey, Ms Lee has remained optimistic. A homemaker when diagnosed, she took up a few part-time roles on top of her advocacy work after her condition stabilised. She has since completed a data engineering course and now has a full-time job as an operations manager at a tech start-up.

Family time is also precious, and she cherishes being able to watch her daughters, now aged 16 and 19, blossom into young adults.

Find out more about Leap here.

References:

1Guirado, M., Fernández, E., Fernández, A., Navarro-Martín, A., Sánchez-Hernández, A. Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review. Clin Transl Oncol. 2022 Aug;24(8):1549-1568. Doi: 10.1007/s12094-022-02796-w. Epub 2022 Mar 7. PMID: 35257298; PMCID: PMC8900646.

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