Standard of Care in SCLC: Treatment Across Limited- and Extensive-Stage Disease

Jacob Sands, MD Dana-Farber Cancer Institute | Rahul Gosain, MD, MBA Wilmot Cancer Institute | Rohit Gosain, MD Roswell Park Comprehensive Cancer Center

Key Points

• The standard of care treatment for small-cell lung cancer (SCLC) in the early-stage setting is resection followed by adjuvant chemotherapy.

• The ADRIATIC study established concurrent chemoradiation followed by 2 years of durvalumab as the standard of care for limited-stage SCLC.

• In extensive-stage patients, the first-line standard of care is chemotherapy plus atezolizumab followed by maintenance with atezolizumab plus lurbinectedin, based on the IMforte trial.

• If patients with extensive-stage SCLC progress on the IMforte regimen, tarlatamab is the preferred second-line treatment based on the DeLLphi-304 trial.

• Across SCLC treatment settings, clinical trials are investigating promising novel agents, and patients should be referred when possible.

Reviewing Standard of Care Treatments for SCLC Populations

Jacob Sands, MD, a thoracic medical oncologist at Dana-Farber Cancer Institute, joined the Oncology Brothers podcast to review standard SCLC treatment algorithms with cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center. The discussion covered the standard of care treatment for SCLC in the limited-stage and extensive-stage settings, which have both seen major updates in recent years. Even with these advancements, many promising clinical trials are underway across SCLC treatment settings, and oncologists should consider referring patients when possible, said Dr. Sands. 

Treatment Algorithm for Limited-Stage SCLC

The doctors first reviewed the treatment algorithm for limited-stage SCLC, including the early-stage setting. While early-stage SCLC is rare, modern lung cancer screening is improving the detection of this population. The standard of care treatment for early-stage SCLC is upfront surgery followed by 4 cycles of adjuvant chemotherapy with a platinum agent plus etoposide. This standard may evolve pending a phase II trial, co-chaired by Dr. Sands, evaluating the addition of durvalumab to adjuvant chemotherapy. 

For the broader limited-stage SCLC population, the standard of care treatment is concurrent chemotherapy and radiation, followed by 2 years of durvalumab based on the ADRIATIC study. ADRIATIC found that adding durvalumab improved median progression-free survival (PFS) by 7.5 months and median overall survival (OS) by 22.5 months. These “astonishing” data further validate the efficacy of durvalumab in SCLC, and very clearly establish chemoradiation followed by durvalumab as the standard of care treatment for limited-stage SCLC, said Dr. Sands.

The use of prophylactic cranial irradiation (PCI) is debated in limited-stage SCLC. Early studies suggested PCI improved survival in both limited-stage and extensive-stage SCLC. However, a 2017 phase III trial from Japan reassessed the efficacy of PCI in patients with extensive-stage SCLC and reported it did not improve survival compared with observation, calling into question the strength of the data supporting PCI in limited-stage SCLC. The ongoing MAVERICK trial will reevaluate PCI across SCLC populations. Still, until that data are available, Dr. Sands has leaned away from using PCI in limited-stage patients given the potential long-term toxicities.

Standard of Care Treatment for SCLC in the Extensive Stage

The first-line standard of care treatment for extensive-stage SCLC is induction with platinum-based chemotherapy plus atezolizumab followed by maintenance with atezolizumab plus lurbinectedin based on the IMforte trial. Like other cytotoxic agents, lurbinectedin is associated with cytopenias, fatigue, and nausea. While these toxicities are familiar and typically resolvable, patients on prolonged lurbinectedin maintenance should be managed carefully so that, if they experience disease progression, they are still eligible for second-line clinical trials. Trilaciclib can be very effective for managing cytopenias in select patients receiving lurbinectedin, Dr. Sands suggested. 

If patients progress on first-line therapy, the second-line standard of care treatment is tarlatamab based on the DeLLphi-304 trial. When starting patients on tarlatamab, community providers may benefit from partnering with hospitals or centers that can support the first treatment cycle where the risk of cytokine release syndrome is highest, said Dr. Sands. After the first cycle, all providers should be able to continue tarlatamab in the outpatient setting.

Alternate standard-of-care second-line treatments for extensive-stage SCLC include lurbinectedin (if patients did not receive it in first-line therapy), topotecan, and single-agent chemotherapy. Rechallenging with platinum-based chemotherapy may be appropriate if at least 6 months have passed since patients were last exposed. Alongside these options, physicians should always consider potential clinical trials.