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Updates in SCLC: Experts Address Questions on Practice-Changing Evidence From 2025 Global Congresses

Released: May 27, 2026

Charles Rudin
Charles Rudin, MD, PhD
Mark A. Socinski
Mark A. Socinski, MD
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Key Takeaways
  • Maintenance therapy with lurbinectedin plus atezolizumab improves survival for patients with extensive-stage small-cell lung cancer, but appropriate patient selection and toxicity management are important.
  • The DeLLphi-304 phase III trial demonstrated significant survival improvements with tarlatamab vs standard chemotherapy as second-line treatment for extensive-stage small-cell lung cancer.

In this expert Q&A commentary, leading thoracic oncology specialists Dr Mark A. Socinski and Dr Charles Rudin address questions related to evolving treatment strategies for limited-stage (LS) and extensive-stage (ES) small-cell lung cancer (SCLC), including the role and duration of immunotherapy consolidation, maintenance therapy, and emerging bispecific antibodies. Faculty review key clinical trial data and provide practical guidance for integrating newly approved therapies and clinical trial options into routine care.

If a patient with LS-SCLC receives less than 2 years of durvalumab consolidation due to intolerance, will they derive the same benefit as a patient who completes therapy?
Mark A. Socinski, MD: The phase III ADRIATIC trial in patients with LS-SCLC did not show that patients who received less than 2 years of durvalumab consolidation derived a similar benefit, but the phase III PACIFIC trial in patients with non-small-cell lung cancer did show an advantage for participants who completed a full year of therapy, where the median number of doses was 20, or around 9 months of therapy. However, whether this advantage was because the patients were more fit or because of the additional doses remains unanswered.

Charles Rudin, MD, PhD: I do not think there are adequate data in LS-SCLC. There have not been many discontinuation trials in this setting to answer the question of how long to give immunotherapy. In my opinion, patients who benefit from immunotherapy do so early during treatment. If therapy is stopped for toxicity concerns, patients can continue to benefit, likely due to persistent antitumor immune activity.

Mark A. Socinski, MD: Following up on that, there are data to suggest that some level of immune-related adverse events may be favorable as long as patients do not develop high‑grade toxicity.

How do you proceed when you see a patient with newly diagnosed ES-SCLC?
Mark A. Socinski, MD: I always think about first steps, whether there is a role for maintenance therapy, and what the next option would be. I aim to maximize the number of effective treatment opportunities available to each patient.

Charles Rudin, MD, PhD: The phase III IMforte trial demonstrated a survival benefit with lurbinectedin plus atezolizumab as maintenance therapy, but this combination came with a higher incidence of adverse events. It is not appropriate for all patients, but for selected patients, like those with a good performance status who want to maximize a positive outcome, it should be considered.

Mark A. Socinski, MD: I currently manage 2 patients with ES-SCLC on lurbinectedin plus atezolizumab as maintenance, and so far, I have been impressed with the tolerability of this combination. My plan is to transition them to tarlatamab upon disease progression. So far, these patients have received 8 or 9 doses of maintenance therapy after 4 doses of induction therapy. It has been almost 1 year of therapy, and they seem to be tolerating it well. I also feel like tarlatamab is a good option following maintenance.

If a patient received prophylactic cranial irradiation (PCI), would you be concerned about an increased risk for immune effector cell–associated neurotoxicity syndrome (ICANS) associated with tarlatamab?
Mark A. Socinski, MD: I personally have not seen any correlation between prior PCI and an increased risk for ICANS with tarlatamab, but ICANS is a relatively uncommon event, and we are still in the early days of using tarlatamab. In ES disease, I have shied away from considering PCI, as have our radiation oncologists. Instead, we prefer brain monitoring with MRI rather than exposing patients to PCI.

Do you think tarlatamab will move into LS-SCLC or into earlier settings for ES-SCLC?
Mark A. Socinski, MD: I am optimistic that tarlatamab will move into the first-line setting for ES-SCLC pending results from the phase III DeLLphi-305 trial (NCT06211036). I was impressed with the results from DeLLphi-304, which demonstrated significant survival improvements with tarlatamab vs standard chemotherapy as second-line treatment. I think that as tarlatamab moves into the first-line setting, the benefits could be similar, if not greater.

Charles Rudin, MD, PhD: I share your enthusiasm, but of course we need the data. I think it is likely to be more difficult to position tarlatamab in LS-SCLC because it must prove itself better than agents already available in that setting.

How do you see obrixtamig fitting into the treatment landscape for relapsed SCLC?
Charles Rudin, MD, PhD: The dose-escalation phase I DAREON™-9 trial is looking at obrixtamig plus topotecan in patients with relapsed SCLC. There is concern about additive toxicity when combining these agents, as topotecan is not always the easiest agent to combine with, but the interim analysis showed that this combination was tolerable in the second-line setting. Moreover, the combination showed a partial response rate of 65%, with essentially all patients showing at least disease control and no primary progressors. It is an interesting combination, but it is difficult to know what its future looks like, particularly now that tarlatamab is approved. Nevertheless, obrixtamig is clearly an active agent.

Considering there are more smokers in Europe and Asia, is there further research for SCLC beyond the United States?
Charles Rudin, MD, PhD: Yes, much research is happening in Europe and Asia. Most of the initial lurbinectedin trials were conducted in Europe. Drug development in China is exploding: many interesting agents are currently being developed there. Cancer research—not only lung cancer—has become global, with major efforts in Asia that are, in many ways, leading the field.

What are your thoughts on cancer vaccines in SCLC?
Charles Rudin, MD, PhD: Attempts to grind up a tumor and use it as a vaccine have been made, but this is not an effective oncological approach. At present, there is quite a lot of interest in cancer vaccines designed around cancer antigens. Some of the same mRNA technology used to develop the COVID-19 vaccines is being deployed in the context of cancer. I think it is an interesting area, but it is too early to know how it will play out. As we are beginning to better understand how to stimulate an immune response in a cancer, this area could expand rapidly over the next decade.

What advice do you have for community oncologists who manage patients with SCLC?
Mark A. Socinski, MD: Over the past 5 or 6 years, several therapies, including immunotherapy, lurbinectedin maintenance, and tarlatamab, have been added to the armamentarium. My advice for community oncologists is that when you see a new patient with ES-SCLC, you should consider the potential benefits of all these drugs. This requires vigilance in monitoring for progression, carefully selecting patients for maintenance therapy, and managing the side effects of each treatment. Not every patient is going to receive all these therapies, so I recommend an approach whereby the goal is to achieve the best possible outcome with our current options.

Charles Rudin, MD, PhD: I agree. For community oncologists, the NCCN guidelines are a very important resource. Understanding the roles of immunotherapy, tarlatamab, and lurbinectedin is important, as these drugs have become standards of care that community oncologists should be aware of. For patients who are not responding to these agents, referral to a tertiary care center and/or enrollment in a clinical trial with an emerging therapy should be considered. I think understanding the basics is key.

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