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SCLC treatment FAQ
Answers to Your Questions on the Evolving Treatment Paradigm in SCLC

Released: July 22, 2025

Expiration: January 21, 2026

Melissa L. Johnson
Melissa L. Johnson, MD
Ticiana Leal
Ticiana Leal, MD
Mark A. Socinski
Mark A. Socinski, MD
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Key Takeaways
  • Durvalumab consolidation therapy is now standard of care following first-line chemotherapy for patients with limited-stage small-cell lung cancer (SCLC) and good performance status based on significantly improved progression-free survival and overall survival (OS) compared with placebo in the ADRIATIC trial.
  • The addition of lurbinectedin to maintenance immunotherapy is currently under FDA review for possible approval based on the IMforte trial that showed improved median OS.
  • Novel therapies including DLL3-targeted T-cell engagers and antibody–drug conjugates are improving outcomes in patients with previously treated extensive-stage SCLC.

This commentary summarizes key discussions and expert insights from a recent symposium on advancing small-cell lung cancer (SCLC) treatment, featuring Melissa L. Johnson, MD; Ticiana Leal, MD; and Mark A. Socinski, MD. This commentary captures their responses to important questions submitted by the audience of healthcare professionals related to the evolving landscape of SCLC therapy including the use of consolidation immunotherapy for limited-stage disease, novel agents, and key clinical decisions in both limited-stage and extensive-stage disease. These advancements are reshaping SCLC clinical management.

LS-SCLC Treatment: Current Standard of Care

Mark A. Socinski, MD:
Radiotherapy advancements have significantly affected our treatment approach for limited-stage (LS) SCLC. A landmark Turrisi trial published in 1999 demonstrated 10% improved survival with twice-daily radiotherapy concurrent with chemotherapy compared with once-daily administration (45 Gy), establishing twice daily as the standard schedule. Follow-up trials have examined more intensive radiotherapy, but optimal fractionation has yet to be conclusively established.

However, a clear clinical benefit for consolidation immunotherapy following chemoradiotherapy was seen in the ADRIATIC trial. Durvalumab treatment up to 2 years significantly improved median overall survival (OS) (55.9 vs 33.4 months; HR 0.73) and progression-free survival (PFS) (16.6 vs 9.2 months; HR: 0.76) compared with placebo, becoming the new NCCN standard of care for LS-SCLC. The inclusion of immunotherapy, either concurrent with or following chemoradiotherapy, is the subject of more recent and ongoing studies. Unfavorable results presented last year from NRG-LU005 found no survival advantage with concurrent use of atezolizumab continuing for 1 year post treatment.

What could explain the differences in efficacy outcomes between the ADRIATIC trial (durvalumab consolidation) and the NRG-LU005 trial (concurrent atezolizumab) in LS-SCLC?

Melissa L. Johnson, MD:
The critical difference likely involves timing. In NRG-LU005 atezolizumab was administered concurrently with radiation, potentially suppressing immune responses because of impaired lymph node drainage. Similar unfavorable findings were noted with concurrent immunotherapy in PACIFIC-2 in NSCLC and other trials in head and neck cancers, supporting sequential immunotherapy after radiation as more effective.

Should patients who relapse after completing 2 years of consolidation durvalumab in LS-SCLC be retreated? Should we consider switching immunotherapies?

Ticiana Leal, MD:
Retreatment with platinum-based chemotherapy plus immunotherapy could be appropriate in patients who showed prior response. Switching from durvalumab to atezolizumab is an option, although it currently lacks robust evidence. Addressing immunotherapy resistance is becoming increasingly important.

Melissa L. Johnson, MD:
Switching immunotherapies (i.e., atezolizumab for ES-SCLC after durvalumab for LS-SCLC) mainly provides psychological reassurance to the doctor rather than clinical necessity for the patient. Nonetheless, retreatment with platinum-based chemotherapy and immunotherapy remains a logical clinical approach.

With durvalumab consolidation becoming standard, when should prophylactic cranial irradiation (PCI) ideally be administered?

Mark A. Socinski, MD:
In ADRIATIC, PCI was administered before starting durvalumab. In clinical practice, close collaboration with radiation oncology will be needed to initiate durvalumab within the recommended 42-day window post chemoradiotherapy.

Melissa L. Johnson, MD:
PCI can take 3 weeks, underscoring the need for careful schedule coordination.

Optimizing First-line Therapy for ES-SCLC: Current Standard of Care

Mark A. Socinski, MD:
First-line extensive-stage (ES) SCLC therapy has also evolved significantly with the introduction of immunotherapy. The pivotal trials IMpower133 and CASPIAN showed clear survival benefits with the addition of atezolizumab or durvalumab, respectively, to chemotherapy, and these regimens are now integrated into standard of care.

Regarding thoracic radiotherapy in ES-SCLC, in what clinical scenarios might stereotactic body radiation therapy (SBRT) be appropriate rather than traditional fractionation?

Mark A. Socinski, MD:
Existing thoracic radiotherapy data such as the Slotman trial (30 Gy in 10 fractions) employed conventional fractionation. SBRT has not been established for thoracic disease in ES-SCLC.

Ticiana Leal, MD:
Current trials of thoracic radiation in combination with immunotherapy use lower doses than SBRT. Caution is needed when combining SBRT with immunotherapy because of potential toxicity. Currently SBRT is typically reserved for palliation of limited metastatic disease such as bony sites rather than primary thoracic treatment.

Lurbinectedin: A Promising Maintenance Therapy

Melissa L. Johnson, MD:
Lurbinectedin has emerged as an FDA-approved option for patients with relapsed metastatic SCLC. More recently, the IMforte trial investigated lurbinectedin combined with atezolizumab as first-line maintenance therapy following induction chemotherapy for ES-SCLC. The trial demonstrated a significant median OS improvement from 10.6 months (atezolizumab alone) to 13.2 months with the combination (HR 0.73), suggesting a transformative role in prolonging patient survival and is currently under FDA review for this indication.

What were the IMforte OS outcomes from the initiation of induction chemotherapy, and how do these compare with historical outcomes?

Mark A. Socinski, MD:
The reported IMforte OS figures are calculated from the beginning of maintenance therapy. Including the induction chemotherapy period (approximately 3 months), OS approaches 16-17 months, marking one of the most substantial survival outcomes in ES-SCLC to date.

Emerging Novel Targets and Therapeutic Strategies

Melissa L. Johnson, MD:
Tarlatamab, a DLL3/CD3 bispecific T-cell engager, provides a novel targeted approach for patients with pretreated ES-SCLC. FDA approval in this indication was based on phase II efficacy, which included intracranial activity. Now the phase III DeLLphi-304 trial has reported a survival benefit of tarlatamab over chemotherapy (median OS: 13.6 vs 8.3 months; HR 0.60) in patients with progressive/relapsed SCLC of any stage. The safety of tarlatamab in combination with durvalumab as first-line maintenance therapy has also been established, and efficacy is being investigated in the phase III DeLLphi-305 trial. Monitoring for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) is necessary with tarlatamab. These adverse events occur primarily during early treatment cycles and can be managed with detailed guidelines included in the prescribing information.

Ticiana Leal, MD:
Several antibody–drug conjugates (ADCs) are currently under investigation in SCLC. Ifinatamab deruxtecan (I-DXd) (targeting immune checkpoint molecule B7-H3) has demonstrated impressive early efficacy (overall response: ~55%) in patients with pretreated ES-SCLC, including those with brain lesions. I-DXd trials are ongoing in the progressive/relapsed setting and in combination with atezolizumab maintenance.

Could ADCs such as I-DXd or T-cell engagers potentially move to frontline ES-SCLC therapy?

Ticiana Leal, MD:
This is currently premature, although some early data have indicated promising synergy. The DLL3/CD3 bispecific antibody obrixtamig in combination with topotecan showed an approximately 70% response rate in progressive/relapsed disease in the DAREON-9 trial. If confirmed, the combination of a T-cell engager with a topoisomerase inhibitor could be strong enough to reshape frontline strategies, although careful toxicity management would be essential. Durability of response would also be a key factor to translate early symptomatic relief into survival benefit, which is not seen with frontline etoposide and carboplatin.

Melissa L. Johnson, MD:
Provocatively, an ongoing trial replaces etoposide with I-DXd as part of first-line therapy, given promising early phase trial data. Carboplatin and etoposide have been given in combination for 30 years, and the degree to which either agent is responsible for the response is unknown. It may be that an ADC will provide early response and a T-cell engager will provide durable response. However, robust clinical validation demonstrating superior outcomes without undue toxicity is necessary.

Your Thoughts
Are you using consolidation therapy with durvalumab for patients with LS-SCLC in your current practice? What challenges or unanswered questions do you have about integrating novel therapeutic strategies into your clinical management of patients with SCLC?

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