‘Never Give Up’: Treatment Breakthroughs Arrive for SCLC

Photography by Jill Stiffler

For Sabrina Potts, the approval by the Food and Drug Administration (FDA) of Imdelltra (tarlatamab-dlle) in May 2024 for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) was an answer to her prayers.

Potts, now 58, received her diagnosis of SCLC in mid-2023. Amid a tumultuous treatment journey, she says the prospect of Imdelltra’s approval “gave me a reason to keep on going.”

“For a while, things were looking a little grim,” says Potts, who lives in Plumville, Pennsylvania. “And then, this really uplifted me.

“You know, I had been praying for something, a miracle, anything. I’m a true believer in God. And I do believe that he has a hand in all this.”

Before her diagnosis, Potts says, she was energetic, and had worked as a nurse for 25 years before retiring 15 years prior. ”I got the lung cancer diagnosis, and I started going downhill from there,” she says.

“After having severe upper respiratory infections and visiting my primary care provider multiple times, the physician’s assistant, Megan Shugarts, ordered chest X-rays and found a large tumor in my right lung,” Potts says. “Later I began treatment with Dr. Daniel Petro, and his outstanding team. After being seen by them everything went into fast speed, or seemed like it.”

Potts, who is being treated at UPMC Hillman Cancer Center in Pittsburgh, learned that her cancer had spread to her liver and her lymph nodes, and was treated with chemotherapy and radiation. By early 2024, it had further metastasized to areas including her bones and her stomach. She was hospitalized for pneumonia, and then for pain from a rib that had been fractured by persistent coughing.

She began treatment with Imdelltra in June, and says by late August, she felt better than she had prior to her diagnosis. Regarding side effects, in addition to a headache after her first treatment, she has experienced nausea, fever, extreme lethargy, increased pain and an unsteady gait, she says.

Taking a Bite Out of Cancer

Imdelltra is a type of immunotherapy known as a bispecific T-cell engager, or BiTE therapy, which binds to both cancer cells and immune cells, bringing them into close proximity and allowing the patient’s own T cells to attack tumor cells.

“It essentially forces an interaction between the tumor and the T cells that are otherwise repelling or ignoring one another,” says Dr. Carl Gay of the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston. “In doing so, the T cells finally gain access to the tumor, and seemingly recognize they’ve been sleeping on the job, and go about their expected role of attacking the tumor and eliminating at least a portion, if not, in some cases, nearly all of the tumor in some of the patients that have received this therapy.”

The accelerated FDA approval of Imdelltra for patients with ES-SCLC (cancer that has spread throughout the lung to the other lung, or to other parts of the body, according to the American Cancer Society) with disease progression on or after platinum-based chemotherapy was based on phase 2 results from the DeLLphi-301 clinical trial presented at the 2023 European Society for Medical Oncology Congress and published in The New England Journal of Medicine.

Among patients with relapsed/refractory ES-SCLC whose disease progressed after treatment with platinum-based chemotherapy, the objective response rate (patients who responded partially or completely to treatment) was 40%, with a median duration of response of 9.7 months, the FDA reported.

According to the FDA, the prescribing information for Imdelltra includes a boxed warning for serious or life-threatening cytokine release syndrome (CRS) and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS), both consequences of exuberant activation of the immune system and injury to normal cells.

CRS involves symptoms such as fever, nausea, rash, headache, low blood pressure, rapid heartbeat and difficulty breathing after the rapid release of proteins known as cytokines into the blood. ICANS may have symptoms including delirium, confusion, seizures and language difficulties.

“You’re awakening the immune system, and that can be good, bad or even both at the same time,” says Gay.

The most common side effects experienced by more than 20% of patients included CRS, fatigue, pyrexia (fever), dysgeusia (altered taste), decreased appetite, musculoskeletal pain, constipation, anemia and nausea, the agency reported, noting that the most common grade 3 (severe) or 4 (life-threatening) laboratory abnormalities among more than 5% of patients were decreased lymphocytes (a type of white blood cell), decreased sodium, increased uric acid, decreased total neutrophils (a type of white blood cell), decreased hemoglobin (a protein in red blood cells), increased activated partial thromboplastin time (slow blood clotting) and decreased potassium.

“Fortunately, these side effects with [Imdelltra] have proved to be mild and manageable, at least in the trials that led to its approval,” Gay says. “I think we’re all now getting our first experience with treating patients like this in the standard of-care setting.”

Decades of Disappointment

Treatment advancements for SCLC are few and far between, experts note. It has been traditionally considered one of the most aggressive and treatment-refractory cancers. Physicians who spoke with CURE cite obstacles to treatment such as a tendency for SCLC to be diagnosed at late stages and the frequency with which patients relapse after initially responding to treatment.

“We’ve suffered through decades of disappointment in small cell lung cancer, or maybe modest advances at best,” Gay says.

“The limited options of treatment for patients with small cell lung cancer is the reality that we all confront — but that is not for lack of trying,” says Dr. Taofeek K. Owonikoko, executive director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore.

Owonikoko is also the senior associate dean of cancer programs at University of Maryland School of Medicine and the associate vice president of cancer programs at University of Maryland, Baltimore.

“Unlike other forms of lung cancer, where we now have more than 30 approved drugs for, comparatively speaking, a cancer type that starts in the same organ system as small cell lung cancer, one key difference between small cell and non-small cell types of lung cancer is the fact that the past 20 years brought a lot of revolution and innovation in carving out discrete populations of non-small lung cancer patients that we used to lump together as a single cancer type and recognizing them as different from one another, and potentially also responding to different treatment approaches,” Owonikoko says. “So we’ve gone from looking at non-small cell lung cancer as just … two or three different types of cancer … to where we now define them by a mutation that is present within the tumor cells, along with certain expression of biomarkers like PD-L1, HER2, and c-MET present on the surface of the tumors. And combining that approach with efforts to develop new drugs resulted in a plethora of therapeutic options for patients with non-small cell lung cancer. Small cell lung cancer, on the other hand, continues to be viewed as just one disease entity. And we treat all those patients as the same. I think that approach has contributed in no small way to the limited success that we’ve witnessed in the small cell space.”

'Nothing Has Recurred, Nothing Has Advanced'

Photography by Lindsay Ritchie

It was late 2018 when Jennifer Sanborn began experiencing a dry cough, something a physician’s assistant attributed to bronchitis and treated with antibiotics. After the cough persisted for a month, Sanborn’s physician ordered a chest X-ray, which revealed a mass in her right lung.

Within two weeks Sanborn had connected with Dr. Yuanbin Chen of the Cancer and Hematology Centers in Grand Rapids and Norton Shores, Michigan, and had begun a course of chemotherapy and radiation. Chen then approached her about potentially participating in a clinical trial.

“I instantly said, ‘Yes, of course,’” recalls Sanborn, now 65, who lives in Michigan.

Chen was among the researchers on the landmark phase 3 ADRIATIC trial of Imfinzi (durvalumab). The drug, an immunotherapy that the FDA had approved in 2020 in combination with etoposide and either carboplatin or cisplatin as first line treatment of ES-SCLC following results of the CASPIAN trial, was tested in ADRIATIC among patients such as Sanborn who had limited-stage (cancer that is only on one side of the chest, according to the American Cancer Society) SCLC and whose disease had not progressed after chemoradiotherapy.

Results of the trial, which made waves earlier this year at the American Society of Clinical Oncology Annual Meeting and were published in the Journal of Clinical Oncology, showed that at a median follow-up of 37.2 months, the median overall survival (the time a patient lives following treatment, regardless of disease status) was 55.9 months among patients treated with Imfinzi versus 33.4 months among patients treated with placebo. Median progression-free survival (how long a patient lives without their disease spreading or worsening) was 16.6 months and 9.2 months, respectively.

“This is perhaps the only breakthrough advancement in the past 30 years, because we have been using chemotherapy and radiation to treat [patients with] limited-stage small cell lung cancer since more than 30 years ago. However, this is the first time a new treatment has been shown to be able to prolong life for almost two years,” Chen says.

An immunotherapy known as a monoclonal antibody, Imfinzi “works by helping a patient’s immune system, to allow a patient’s own immune system to go attack the cancer and shrink the cancer and kill the cancer cell,” Chen says. Imfinzi specifically blocks the protein PD-L1, which helps the immune system detect and attack cancer.

Researchers reported that 24.3% of patients treated with Imfinzi experienced grade 3 or 4 side effects, with side effects leading to treatment discontinuation in 16.3% of patients and death in 2.7% of patients. Any-grade pneumonitis/radiation pneumonitis (inflammation of the lung tissue) was reported in 38% of patients treated with Imfinzi.

After her initial treatment, Sanborn says she felt like she came down with the flu, experiencing aches, chills and sickness to her stomach.

She initially received scans every three months and is now checked every six months, she says. “Nothing has recurred, nothing has advanced, nothing. I’ve never heard the word ‘remission’ because I don’t know if that exists in this cancer area,” she says.

Over time, her mindset toward scans has changed, she explains.

“[Initially] you’re … looking for days to get the results, and it’s like [you’re] on pins and needles,” she says. “And now I’m to the point where I get them, and I am not on pins and needles. I don’t live for that MRI and CT scan, whereas before, that’s what I was living for, just to be clear, you know? It’s like, ‘Am I going to be OK? Is this just going to come back? Am I going to have to go through the chemo again?’ And no. And I wondered that I’d ever get to this point where I was not dreading that and looking forward to it at the same time.”

Elsewhere, progress continues, with an announcement in August 2024 that the FDA had granted a breakthrough therapy designation to GSK5764227 (GSK’227), an antibody-drug conjugate being evaluated for the treatment of patients with ES-SCLC. Antibody-drug conjugates deliver chemotherapy directly to cancer cells with the intention of sparing healthy cells from harmful effects.

Although this year has seen great strides in treating patients with SCLC, Owonikoko says that unmet needs remain — namely, a cure.

“While the ADRIATIC trial, the CASPIAN trial [and] the [DeLLphi-301] trial [have] all shown good advances in what these treatment options bring for our patients, we’re still far, far away from where we need to be,” he says, “which is, how do we transform small cell lung cancer from being a very mortal diagnosis to something that people can survive? We are beginning to move ahead from wanting to just turn cancer into a chronic illness to trying to cure it.

“And all of these options, while they are really beneficial and with great promise for some patient subset, I don’t think we’re at a point where we can be confident that [the] majority of our patients will be cured because of these treatments that we do have now. Is it possible that as we gain more experience that cure could be the expected outcome for some patients? I will say possibly, but for [the] majority of our patients, the current progress is still not something that we can rely on as a cure. It’s benefiting patients, no doubt, and making patients live longer, but not being able to cure a lot of our patients remains an area of unmet need.”

Potts has advice for fellow patients with SCLC: “Never give up,” she says. “I do believe in these doctors. God has given them a gift. And let them use their gift to help you.”

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