Surgical and Radiotherapy Choices in Limited-Stage SCLC

Video content above is prompted by the following:

In your experience, what percentage of limited-stage disease is amenable to resection and does lobectomy remain the preferred procedure for stage I-IIA (T1-2, N0, M0) disease?

does a surgeon operate on a small cell nodule, and what is the next step in treatment? 

Under what circumstances would surgery vs radiotherapy (SABR ) be a preferred, definitive treatment choice for a patient with stage I-IIA small cell lung cancer (SCLC)? 

What factors inform your decision to select systemic treatment and 

ation factor into your treatment plan for patients with limited-stage SCLC?

Videos

Panelists discuss how the surgical approach to limited-stage small cell lung cancer varies, including the percentage of cases amenable to resection, the preference for lobectomy in stage I-IIA disease, and the role of mediastinal lymph node staging in shaping treatment strategies, alongside considerations for choosing between surgery and radiotherapy, the selection of systemic treatments, and the integration of prophylactic cranial irradiation in treatment plans.

Current Landscape of First-Line Treatment for Limited-Stage SCLC: Diagnostic Workup & Multidisciplinary Approaches

Briefly explore the current landscape of 

for limited-stage small cell lung cancer (LS-SCLC):

What clinical factors influence the initial diagnostic workup and managementof patients with LS-SCLC? 

approach adopted when developing a treatment plan for patients with LS-SCLC? 

Panelists discuss how the current landscape of first-line treatment for limited-stage small cell lung cancer is shaped by various clinical factors that influence the diagnostic workup and management, emphasizing the importance of a multidisciplinary team approach in developing effective treatment plans for these patients.

Triparna Sen, PhD, discusses updated findings from the phase 3 MARIPOSA study (NCT04487080).

Dr Sen on Interim IDeate-Lung01 Data in Extensive-Stage SCLC

Triparna Sen, PhD, cell and molecular biologist, associate professor, Department of Oncological Sciences, director, Lung Cancer PDX Platform, Icahn School of Medicine at Mount Sinai, discusses findings from an interim analysis of the phase 2 IDeate-Lung01 trial (NCT05280470), which is evaluating the B7-H3–directed antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in patients with extensive-stage small cell lung cancer. 

IDeate-Lung01 enrolled patients who had undergone at least 1 line of prior platinum-based chemotherapy and no more than 3 prior lines of systemic therapy. Patients were randomly assigned 1:1 to receive I-DXd every 3 weeks at a dose of 8 mg/kg (n = 46) or 12 mg/kg (n = 42), Sen explains.

Data from an interim analysis of IDeate-Lung01 presented during the 

2024 IASLC World Conference on Lung Cancer

demonstrated that patients who received the 12 mg/kg dose achieved an objective response rate per blinded independent central review of 54.8% (95% CI, 38.7%-70.2%) compared with 26.1% (95% CI, 14.3%-41.1%) in the 8 mg/kg arm, Sen says. The disease control rate (DCR) was 90.5% (95% CI, 77.4%-97.3%) vs 80.4% (95% CI, 66.1%-90.6%), respectively. However, the median duration of response was 4.2 months (95% CI, 3.5-7.0) compared with 7.9 months (95% CI, 4.1-not estimable).

The 12 mg/kg dose was selected as the recommended dose of I-DXd for the second part of IDeate-Lung01 and for the phase 3 IDeate-Lung02 study (NCT06203210). Although these data are promising, further research into the toxicity profile of I-DXd is needed and the full data from the study will need to be analyzed, Sen concludes.

Triparna Sen, PhD, discusses findings from an interim analysis of the phase 2 IDeate-Lung01 trial in patients with extensive-stage small cell lung cancer. 

Dr Sen on the Goal to Identify Actionable Biomarkers of Interest in SCLC

Triparna Sen, PhD, cell and molecular biologist, associate professor, Department of Oncological Sciences, director, Lung Cancer PDX Platform, Icahn School of Medicine at Mount Sinai, discusses the importance of identifying actionable or targetable biomarkers for the treatment of patients with small cell lung cancer (SCLC).

Identifying effective biomarkers for SCLC is challenging, Sen begins, as SCLC doesn’t lend itself to mutation-driven biomarkers due to its high mutation rate, often resulting from patients’ long histories of smoking. This makes mutation-based biomarkers ineffective when making clinical decisions in SCLC, she explains. Consequently, research focuses in SCLC have shifted to expression-based biomarkers, which are more dynamic and complex to implement, Sen reports.

At present, there are no established biomarkers for selecting SCLC treatments; however, developments are emerging in both preclinical and clinical research, she continues. One key area of exploration involves identifying distinct subtypes of SCLC, according to Sen. These subtypes are characterized by transcriptomic and proteomic profiles, and can be broadly divided into 4 categories, including major neuroendocrine subtypes, non-neuroendocrine subtypes, and prominent immune gene signatures, Sen states. However, these subtypes require validation through prospective clinical trials to determine their relevance as biomarkers, she elucidates.

There is a potential need to reclassify these SCLC subtypes because they might represent different cell states rather than distinct categories, she says. Sen also highlights the biomarker Schlafen 11 (SLFN11), which was initially evaluated in preclinical studies and retrospectively validated in a trial involving veliparib (ABT-888) and temozolomide (Temodar). SLFN11 was later prospectively evaluated in the phase 2 SWOG S1929 trial (NCT04334941). This trial selected patients with SCLC based on SLFN11 expression levels and tested the efficacy of combining a PARP inhibitor with immunotherapy, she explains. The results indicated that patients with high SLFN11 expression hadmarginally better progression-free survival outcomes than those with low SLFN11 expression, Sen adds.

Although these findings demonstrate the potential for biomarker-driven treatment approaches in SCLC, they also underscore that more research is needed, she expands. The field is still evolving, and there is a significant amount of work required to refine and validate these biomarkers before they can be reliably used in clinical settings, Sen concludes.

Triparna Sen, PhD, discusses the importance of identifying actionable or targetable biomarkers for the management of small cell lung cancer.

Triparna Sen, PhD

Articles

Surgical and Radiotherapy Choices in Limited-Stage SCLC

Current Landscape of First-Line Treatment for Limited-Stage SCLC: Diagnostic Workup & Multidisciplinary Approaches

Dr Sen on Interim IDeate-Lung01 Data in Extensive-Stage SCLC

Dr Sen on the Goal to Identify Actionable Biomarkers of Interest in SCLC