Holistic considerations for developing an ES-SCLC treatment plan
Key Takeaways
ES-SCLC is aggressive, with a 5-year survival rate under 2%, necessitating early, honest discussions about treatment goals focused on disease control rather than cure.
Chemoimmunotherapy is standard first-line treatment for ES-SCLC, with newer options such as tarlatamab and lurbinectedin available.
When standard treatments are no longer effective or tolerable, the focus should shift to palliative care and psychological support to maintain patient comfort and dignity.
While there has been great progress in regards to treating non-small cell lung cancer (NSCLC), options for the management of small cell lung cancer (SCLC) remain limited. However, a recent development has offered some hope.
On August 20, 2024, the FDA granted Breakthrough Therapy Designation to GSK5764227 (HS-20093), a novel B7-H3-targeted antibody-drug conjugate linked to a topoisomerase inhibitor, for patients with extensive-stage SCLC (ES-SCLC) who are progressing after platinum-based chemotherapy.[]
The challenging nature of SCLC, combined with the typically late stage at which it is detected and the limited availability of clinical trial data, contributes to a poor prognosis. For ES-SCLC, which is a more advanced form of the disease, the 5-year survival rate is below 2%.[] Many patients face difficulties with aggressive treatments, which often means that palliative care becomes the primary option.
An aggressive and challenging disease
The “extensive stage” in SCLC means the cancer has spread beyond the lungs, and treatment therefore usually centers around slowing the progression of the disease while providing supportive care.
Board-certified oncologist and hematologist Daniel Landau, MD, explains: “Many patients are not aware that they have this disease until they suddenly develop an unexpected symptom like the superior vena cava syndrome.”
He notes that the rapid growth of the cancer can put pressure on the blood vessels above the lungs and cause alarming symptoms like arm or neck swelling. In rare cases, it can cause stroke-like symptoms, severe headaches, or unexplained anemia due to bone marrow suppression.
Managing ES-SCLC also involves monitoring for emergencies, such as spinal cord compression and electrolyte imbalances—particularly hyponatremia from SIADH.
Core treatment approaches
Chemotherapy
The backbone of ES-SCLC treatment traditionally involves chemotherapy, but as Dr. Landau points out, “Chemotherapies unfortunately cause traditional chemotherapy toxicities like hair loss, nausea, and fatigue.” These are the side effects that patients often feel acutely.
Dr. Landau also stresses the importance of being aware of the less visible toxicities that can be just as dangerous, such as kidney damage, anemia, and electrolyte abnormalities. "It's not unusual that we have to give patients IV fluids or electrolyte infusions to help them get through these toxicities," he adds.
Immunotherapy
Immune checkpoint inhibitors targeting the PD-L1 receptor have emerged as a valuable tool in the fight against ES-SCLC. As Dr. Landau explains, “Immunotherapies can affect nearly any part of the body. When the immune system is fired up, it can target legitimately anything.”
He notes the broad potential for side effects, however, such as skin rash, thyroid dysfunction, and even myocarditis. If severe reactions occur, oncologists must be ready to withhold treatment and use immunosuppressants, such as steroids.
Anticipatory management of side effects
Anticipating the likely side effects of chemoimmunotherapy ahead of time and taking appropriate measures to prevent them at the outset can be a fruitful strategy for maintaining the patient’s quality of life during treatment.
Board-certified oncologist Sandeep Nayak, MBBS, MRCS (UK), DNB, emphasizes the need for regular monitoring and preventive measures, particularly to mitigate the impact of treatment on blood cell counts.
He advocates for regular blood tests for early side effect detection, as it allows for timely intervention if such issues arise (eg, neutropenia or anemia). His personal suggestion includes “prophylactic antibiotics or growth factors to reduce the risk of infections or neutropenia.”
Tumor lysis syndrome can also occur rapidly after starting chemotherapy. It can be prevented by ensuring that the patients are well-hydrated and premedicated with allopurinol.[]
The role of emerging therapies
In patients who don’t have a good response to first-line therapy, an alternate regimen can be discussed. Dr. Nayak emphasizes the potential of “targeted therapies [and] combination therapies” as part of the evolving treatment landscape.
In this regard, Dr. Landau is particularly optimistic about the future of bispecific T-cell engager immunotherapy (BiTE). “Bispecific antibodies are a treatment that essentially attaches to both the immune cell and the cancer cell, forcing the immune cell into the cancer cell. This has been proven effective in several cancers, and we suspect it will be the future of care for small cell cancers as well,” he explains.
The FDA has granted accelerated approval to tarlatamab, the first BiTE for ES-SCLC unresponsive to platinum-based chemotherapy.[] The drug has a manageable safety profile, marking a potential milestone in managing small cell cancers.
It should be noted, however, that the phase 2 study only included patients with good performance status.
Patient-centered care
Dr. Landau is candid about the prognosis for ES-SCLC patients: "Unfortunately, most patients with ES-SCLC won't be treated with curative intent. Most of the treatments are to control the disease and help patients live as long as possible." This reality necessitates difficult conversations with the patients and caregivers early to ensure they understand their options and potential outcomes.
"Sometimes, patients tell us they don't want too many side effects and would rather focus on less aggressive therapies and more on quality of life,” Dr. Landau explains.
"It's not considered 'giving up.' It's a change in focus."
— Daniel Landau, MD
Dr. Nayak concurs, stating, “Patient preferences and values should be a priority in treatment decisions.”
If platinum-based chemotherapy is intolerable, oncologists may reduce the dose or try an alternative chemotherapy, like lurbinectedin. When even these modifications are not feasible, palliative care for managing symptoms becomes the primary approach to ensure comfort and dignity in the patient's remaining time.
What this means for you
The FDA recently granted Breakthrough Therapy Designation to a novel B7-H3-targeted antibody-drug conjugate linked to a topoisomerase inhibitor for ES-SCLC progressing after platinum-based chemotherapy. Despite advancements, ES-SCLC treatment remains limited with a poor prognosis, necessitating a focus on symptom management and quality of life. Emerging therapies, including bispecific T-cell engagers, offer new options but require careful management of significant side effects.