Ask AI
Back Back
Care for Veterans With SCLC
Enhancing Care for Veterans With Small-Cell Lung Cancer: Integrating Immunotherapy and Emerging Therapies to Improve Outcomes

Released: November 07, 2025

Mark A. Socinski
Mark A. Socinski, MD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • LS-SCLC: Durvalumab consolidation following concurrent chemoradiotherapy is the standard of care, significantly improving OS and PFS in patients enrolled in ADRIATIC and is now a preferred approach.
  • ES-SCLC: The preferred first‑line treatment option remains platinum/etoposide plus a PD‑L1 inhibitor (atezolizumab or durvalumab), showing consistent survival benefits. The IMforte trial supports the use of lurbinectedin combined with atezolizumab as maintenance therapy following induction for ES-SCLC, showing superior OS and PFS vs atezolizumab alone.
  • Relapsed ES‑SCLC: Tarlatamab and lurbinectedin represent important additions to the treatment arsenal for relapsed ES-SCLC; investigational agents such as sacituzumab govitecan (TROPiCS-03) and ifinatamab deruxtecan (IDEATE-Lung01) are showing promising results in early-phase trials.

Introduction
Emerging data continue to reshape the treatment paradigm for small-cell lung cancer (SCLC) across disease stages. These advances with novel agents and new combination approaches in extensive-stage (ES) SCLC reflect meaningful progress in a historically treatment-refractory disease. As the treatment paradigm continues to evolve, the importance of timely diagnosis, multidisciplinary collaboration, and equitable access to these approaches, particularly within veteran populations, is necessary to optimize clinical outcomes.

LS-SCLC: The Case for Consolidation Immunotherapy
The phase III ADRIATIC trial, which evaluated durvalumab vs placebo after concurrent chemoradiotherapy (cCRT), established the current standard of care for limited-stage (LS) SCLC. This trial demonstrated a significant improvement in overall survival (OS) (median 55.9 vs 33.4 months; HR: 0.73; P = .0104) and progression-free survival (PFS) (16.6 vs 9.2 months; HR: 0.76; P = .0161) with durvalumab consolidation vs placebo in patients with stage I/II inoperable or stage III LS-SCLC and no progression after cCRT with 3-4 cycles of platinum and etoposide and radiotherapy. Of importance, 3.1% of patients treated with durvalumab experienced grade ≥3 pneumonitis/radiation pneumonitis, which was similar to placebo (2.6%) and consistent with the established safety profile of durvalumab. These results led to the FDA approval of durvalumab for the treatment of adult patients with LS-SCLC whose disease has not progressed following cCRT.

In contrast, the randomized phase III NRG-LU005 trial enrolled patients to receive atezolizumab concurrently with CRT and then atezolizumab as consolidation vs CRT alone and did not demonstrate a significant improvement in OS or PFS. The differences in the trial designs and subsequent outcomes for the ADRATIC and NRG-LU005 trials reinforce the current practice of utilizing post-cCRT consolidation immunotherapy rather than starting immunotherapy concurrently with CRT.

First-line Treatment of ES-SCLC: Stable Backbone, New Maintenance
In phase III trials of patients with treatment-naive ES-SCLC, both atezolizumab (IMpower133) and durvalumab (CASPIAN) added to platinum/etoposide and followed by maintenance with the immunotherapy yielded consistent OS benefit vs treatment without the immunotherapy. Specifically, in the IMpower133 trial, median OS was 12.3 months with the addition of atezolizumab vs 10.3 months without (HR: 0.76; P = .0154), and in the CASPIAN trial, median OS was 12.9 months with the addition of durvalumab vs 10.5 months without (HR: 0.75; P = .0003).

As a new combination maintenance option, the FDA recently approved lurbinectedin, a marine-derived tetrahydroisoquinoline alkaloid, plus atezolizumab for adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with carboplatin plus etoposide and atezolizumab based on the randomized phase III IMforte trial. This trial reported superior outcomes for the combination vs atezolizumab alone measured from randomization into the maintenance phase (median PFS: 5.4 vs 2.1 months, HR: 0.54, P <.0001; median OS: 13.2 vs 10.6 months, HR: 0.73, P = .017). This combination represents a significant change to the standard of care, offering a novel strategy to delay disease progression and extend survival.

Relapsed ES-SCLC: Expanding Treatment Options
The landscape for relapsed ES-SCLC continues to evolve, bringing new targets and approaches to the second-line and later settings.

Lurbinectedin, which was granted accelerated approval in the second-line setting before the subsequent approval for first-line maintenance, was evaluated in the single‑arm phase II basket B‑005 trial. Among the 105 patients with ES-SCLC after 1 prior chemotherapy-based regimen who enrolled in this trial, the overall response rate (ORR) reached approximately 35%, with higher responses in patients with platinum‑sensitive disease (ORR: 45%). Although the incidence of grade 3 or 4 neutropenia was high (46%), the rate of febrile neutropenia was reported as 5%.

Tarlatamab, a bispecific T-cell engager targeting DLL3 and CD3, received accelerated FDA approval for ES-SCLC with disease progression on or after platinum-based chemotherapy, based on the phase II DeLLphi-301. Recently, the phase III DeLLphi‑304 trial demonstrated improved OS vs standard of care therapy with topotecan, lurbinectedin, or amrubicin (median OS: 13.6 vs 8.3 months; HR: 0.60; P <.001) and PFS (median PFS: 4.2 vs 3.7 months; HR: 0.71; P =.002) in the second-line setting. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) events, which are associated with most bispecific antibody therapies, were typically grade 1-2 and occured early in therapy but require structured monitoring.

Due to the risk of CRS and ICANS, the FDA recommends step‑up dosing schedule for tarlatamab. Patients should be monitored for 22-24 hours from the start of the infusion in an appropriate setting on cycle 1 Day 1 and Day 8 and are recommended to remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from the start of those infusions. Management includes administering supportive care for grade 1 CRS, while grade 1 ICANS requires withholding tarlatamab until resolution. For escalating cases (≥ grade 2), treatment should be withheld and interventions, including tocilizumab for CRS and corticosteroids for both CRS and ICANS, should be utilized.

In contrast, the primary safety consideration for lurbinectedin in combination with atezolizumab is associated with the risk of severe myelosuppression, including neutropenia and thrombocytopenia. To mitigate this risk, primary prophylaxis with granulocyte colony-stimulating factor is recommended. Treatment should only be initiated if the absolute neutrophil count is ≥1500 cells/mm3 and the platelet count is ≥100,000/mm3. Blood counts must be monitored closely prior to each administration, and dose modifications or treatment withholding are necessary for severe or prolonged cytopenias.

Emerging Agents For Patients With ES-SCLC
Although recent approvals have expanded the therapeutic landscape for SCLC, the prognosis for many patients, particularly those with relapsed or refractory disease, remains poor. Continued exploration of novel treatment strategies is essential to address unmet needs, improve survival, and enhance quality of life.

In the phase II TROPiCS‑03 study of second-line sacituzumab govitecan (SG), an ADC targeting TROP-2, the updated ORR among patients with ES-SCLC after first-line platinum-based chemotherapy plus immuno-oncology was 41.9%, with manageable toxicity. This result led to SG receiving Breakthrough Therapy Designation for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy, though it is not yet FDA-approved (phase III trial is ongoing). 

In the phase II IDeate-Lung01 study of the B7‑H3–directed ADC ifinatamab deruxtecan (I‑DXd), patients with previously treated ES‑SCLC experienced clinically meaningful responses (52.4% with 12 mg/kg and 26.1% with 8 mg/kg), leading to I-DXd receiving Breakthrough Therapy Designation for patients with pretreated ES-SCLC; however, it is not yet FDA-approved. 

VA-Focused Equity and Access Considerations
The Veteran’s Health Administration lung cancer initiatives and screening pathways have laid a critical foundation for earlier diagnosis, but the aggressive nature of SCLC still challenges the effectiveness of fixed screening intervals. To advance equity in patient care, especially within integrated systems like the Veteran’s Health Administration, it is essential to address logistical and clinical barriers that impact access and continuity. For example, the following strategies may help to optimize implementation of emerging therapies and supportive care:

  • Tarlatamab Monitoring: Ensure infusion monitoring capacity is aligned with treatment protocols, and consider support for travel/housing, especially for patients living in rural areas, for the required cycle 1 Day 1 and Day 8 observations.
  • IMforte Scheduling: Streamline the maintenance schedule for lurbinectedin plus atezolizumab post induction to ensure continuity of care by promoting consistent follow-up and minimize care disruptions.
  • Supportive Care: Implement early palliative and supportive care consultations to proactively manage symptom burden and treatment-related AEs.

Your Thoughts
These recent approvals and trial readouts significantly change our approach to both LS-SCLC and ES-SCLC. How is your team integrating the new logistical requirements for tarlatamab and the IMforte maintenance regimen into your clinical workflows?

Continue

Poll

1.

Have you integrated newer treatment options, like lurbinectedin and tarlatamab, into your clinical practice?

Submit