Back Back
FAQs: ES SCLC
Answers to Key Questions in the Multidisciplinary Management of Extensive-Stage SCLC Using Novel Therapies

Released: January 22, 2025

Expiration: January 21, 2026

Christine L. Hann
Christine L. Hann, MD, PhD
Ticiana Leal
Ticiana Leal, MD
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Rechallenge with an anti–PD-L1 antibody regimen may be considered for patients with extensive-stage small-cell lung cancer and evidence of disease progression 6 months or more after completing concurrent chemoradiation for limited-stage disease.
  • The DLL3 x CD3 bispecific antibody tarlatamab is a viable option for patients with disease recurrence following progression on first-line treatment with platinum/etoposide chemotherapy and an anti–PD-L1 antibody.
  • DLL3xCD3 bispecific antibody therapy requires close monitoring for cytokine release syndrome and/or ICANS following infusion, including hospital readmission for suitable management of these serious adverse events.

In this commentary, experts address key questions from healthcare professionals (HCPs) on the care of patients with extensive-stage (ES) small-cell lung cancer (SCLC) that were posed during a live webinar on this topic held in January 2025. These responses provide actionable, applicable information that busy HCPs can use in the clinic.

Would you consider rechallenge with an anti–PD-L1 antibody for a patient with ES SCLC who previously received durvalumab in the ADRIATIC study, or would you manage such a patient as second line following progression?  Would there be any benefit to challenging with a different anti–PD-L1 antibody?  

Ticiana Leal, MD:
For a little context, in the phase III ADRIATIC study, patients with limited-stage SCLC who had not progressed after concurrent chemoradiation therapy then received consolidation treatment with durvalumab with or without tremelimumab, or placebo, every 4 weeks for up to 2 years. In that study, we saw that the use of durvalumab following chemoradiation yielded significant improvement in median progression-free survival (16.6 vs 9.2 months; HR: 0.76; P = .02) and median overall survival (55.9 vs 33.4 months; HR: 0.73; P = .01), with an acceptable safety profile.

Regarding rechallenge with an anti–PD-L1 antibody at progression to ES SCLC, because an immune checkpoint inhibitor was used alone as consolidation therapy in the setting of limited-stage SCLC (ADRIATIC regimen), you might want to use it in combination with a platinum-chemotherapy backbone per current standard of care. However, you also have to consider if their disease remains platinum sensitive. And perhaps the other most important question is whether they are still sensitive to immunotherapy as well. I would say that it may be reasonable to reconsider an anti–PD-L1 antibody if the treatment-free interval is 6 to 12 months. A treatment-free interval of less than 6 months would make me less excited about rechallenge with an anti–PD-L1 antibody, in particular because we have other active agents in that setting like tarlatamab, a DLL3 x CD3 bispecific antibody.

When we look at the data from the open-label, phase II DeLLphi-301 trial of tarlatamab, the median overall survival of 15.2 months was seen independent of platinum sensitivity or platinum-refractory disease. Thus, in a patient with rapid disease progression, you may realistically only have one opportunity to change the outcome.

Chirstine L. Hann, MD, PhD: 
I agree with Dr Leal. I would also use a chemotherapy-free interval of 6 months to inform my next step in regard to therapy. I also want to clarify that this is 6 months after completion of chemoradiation, not if they are 6 months out from finishing the ADRIATIC regimen, which includes 2 years of durvalumab. In which case, after 6 or more months they should be rechallenged with the same chemoimmunotherapy. There is a chance that they will still be sensitive. At this time, I do not think we have good data to suggest that a different anti–PD-L1 antibody would do better.

Ticiana Leal, MD:
I agree. I would not rechallenge with a different anti–PD-L1 antibody, but I do think that if patients are in the middle of ADRIATIC and they have progression on the maintenance phase, I probably would rechallenge with platinum/etoposide alone and would not add the immune checkpoint inhibitor back on.

How frequent are your follow-up calls for patients receiving tarlatamab after they are discharged home?

Ticiana Leal, MD:
As you may know, data from the DeLLphi-301 study showed patients receiving tarlatamab have an increased risk of developing cytokine release syndrome (CRS) and immune effector cell‒associated neurotoxicity syndrome (ICANS) during cycle 1 of treatment, which goes down from cycle 2 onwards. These CRS and ICANS risks necessitated implementation of an adverse event mitigation/management program for tarlatamab that incorporates step-up dosing and close monitoring for CRS and ICANS during the first hours and days after initiating therapy. In addition, tarlatamab is recommended to be administered only by a qualified HCP with appropriate medical support to manage potential severe reactions. Also, based on the prescribing information for this agent, we recommend that patients stay within 1 hour of a healthcare facility while receiving this treatment.

As mentioned, cycle 1 is where the highest potential risk of developing CRS events is being closely monitored in an inpatient setting. When patients receiving tarlatamab go home, after cycle 1 Day 1, we have a clinical pharmacist do follow-up within 48 hours. In addition, our patients have a card stating what their treatment is and who to call in the event of an emergency. We also educate the patient and their family members about when to call and/or when to go to the emergency department.

Chirstine L. Hann, MD, PhD:
Our nurse practitioner will call the patient within 24 hours of their infusion and check in with them several times between the discharge and next planned admission. We have had patients return to the hospital for what we thought were potentially ICANS episodes that were later determined not to be ICANS. That is to say that patients can still experience challenges related to their underlying ES SCLC that may need to be addressed as well. It is critical to have an engaged multidisciplinary team to help promptly address the new potential adverse events with some of the newest treatments for ES SCLC. 

Other emerging treatments in clinical trials include the phase I study of BI 764532 (obrixtamig), a DLL3 x CD3 bispecific antibody and the phase I/II trial of MK-6070, also a DLL3 x CD3 bispecific antibody with an anti-albumin domain. Data for both ongoing studies suggest encouraging efficacy and the potential for CRS and ICANS development, suggesting we need to keep educating ourselves and our clinical teams about managing CRS/ICANS with this novel class of agents for ES SCLC.

Your Thoughts?
How do you plan to incorporate novel therapies, including DLL3 x CD3 bispecific T-cell engagers in the care of patients with ES SCLC?

Visit the program page and download the slides on newly diagnosed or recurrent ESCLC to further your learning on this topic. Answer the poll and leave a comment to join the discussion!

Continue

Poll

1.

Are you using tarlatamab for your patients with ES SCLC?

Submit