Emerging Maintenance Strategies May be the Key to Extending Survival in ES-SCLC

The 3-year overall survival (OS) rate for patients with extensive-stage small cell lung cancer (ES-SCLC) remains approximately 18% with current chemoimmunotherapy regimens, leaving most patients to progress on maintenance immunotherapy and underscoring the need for strategies that extend durable disease control beyond frontline treatment.¹ Maintenance approaches incorporating lurbinectedin (Zepzelca) or the T-cell engager tarlatamab-dlle (Imdelltra) are among the strategies under evaluation to move that bar, according to Millie Das, MD, chair of a recent State of the Science Summit™ on lung cancer, which took a closer look at some of these strategies.

“It’s always great to be a part of these lung cancer summits that bring together community and academic oncologists to stay on top of the latest developments with the goal of being able to apply it to the next patient that we see in clinic,” Das said in an interview with OncLive® following the event. “Seemingly, every few months, there are new data and press releases, and [we have to ask ourselves] what do we make of these data that are getting released, and how do we incorporate that into our clinical practice? I find it useful to gather with my colleagues to discuss these new data in the context of actual patients, and that’s what I enjoyed about this State of the Science Summit.”

In the interview, Das, a clinical professor of medicine - oncology, member of Stanford Cancer Institute, chief of Oncology at the VA Palo Alto Health Care System, and associate program director of Oncology Fellowship at Stanford University at Stanford Medicine in California, discussed the current landscape in ES-SCLC, the promise of maintenance strategies with tarlatamab and lurbinectedin, and why biomarker-driven treatment selection remains out of reach for now.

OncLive: The 3-year OS rate with current chemoimmunotherapy regimens sits around 18%. What’s the most promising near-term approach for raising that number further?

Das: Most of our patients are going to progress on maintenance immunotherapy, so I do think the maintenance treatment strategy of adding lurbinectedin or now tarlatamab is going to hopefully raise that bar higher, particularly with tarlatamab, where the goal is to have more patients with durable control. We’re seeing that with the T-cell engagers, so that’s what I’m most excited about. I [believe] that’s going to hopefully be practice changing and will allow for more patients to be on that tail of the curve to be long-term responders to therapy and alive at 3 or 5 years out from the time of initial diagnosis.

The phase 1b DeLLphi-303 (NCT05361395) data showed encouraging survival with tarlatamab plus a PD-L1 inhibitor in the first-line maintenance setting ahead of the randomized DeLLphi-305 (NCT06211036) results. How are you thinking about that signal in clinic today, and are you tempted to use it off label ahead of confirmatory data?

The data that we’ve seen with tarlatamab have been quite exciting. It’s our standard second-line treatment option based upon the data from the randomized phase 3 DeLLphi-304 study [NCT05740566] that were presented at the 2025 ASCO Annual Meeting [ASCO 2025]. There’s a lot of excitement about the data in the maintenance setting, and I agree that the phase 1 data that were presented at the 2025 World Conference on Lung Cancer looks great with an unprecedented OS in that phase 1 study exceeding 2 years.² It is tempting to think about using it, but I wouldn’t use it off label at this time. I’m waiting for that phase 3 study to read out, which I think will happen hopefully in the upcoming months and will further alter our treatment paradigm for our patients with extensive-stage disease.

If DeLLphi-305 is positive, how do you see maintenance treatment for ES-SCLC changing in practice?

Our standard of care is offering patients platinum etoposide with a PD-L1 inhibitor, and I think once we get the data for tarlatamab maintenance and we see the approval, I think most of our patients are going to be going on to tarlatamab as maintenance therapy. We know that there's a big drop-off from first to second-line therapy, and I worry about patients not having access to drugs in the second-line setting due to worsening performance status and you know other factors, and so it is really I think important for us to think about treatment strategies in the maintenance setting so that we can ensure that patients are having access to these drugs and are benefiting from them.

Lurbinectedin plus atezolizumab (Tecentriq) has also shown promise in this setting. If that combination and tarlatamab prove viable, how would you choose between them for a given patient?

The phase 3 IMforte trial [NCT05091567] that was presented at ASCO 2025 led to the FDA approval for lurbinectedin as a maintenance treatment strategy in combination with atezolizumab,³ and it is something that I’m discussing with my patients with extensive-stage disease. The chemotherapy toxicities with lurbinectedin are real, and it’s something that we need to be discussing and seeing whether our patients are up for. Tarlatamab is a little bit of a different discussion. It’s not chemotherapy; it’s a T-cell engager, which has its own unique adverse effects, including CRS [cytokine release syndrome] and ICANS [immune effector cell–associated neurotoxicity syndrome]. As we’re thinking about these maintenance treatment options for our patients, we have to discuss risks and benefits and the costs for the patients in terms of needing to come in to receive these treatments. Right now, with tarlatamab, we’re still having to admit patients for cycle 1 day 1 and day 8, so depending on the patient circumstances, there’s going to be different factors that are going to play into whether they would opt for something like tarlatamab vs lurbinectedin.

Current treatment selection remains largely biomarker-free. Do you see that changing in the near term?

That’s one of the frustrating aspects of SCLC. We’re just not there yet with using biomarkers to select patients. Ongoing trials are attempting to do this, but I worry that SCLC is a very heterogeneous disease, so trying to select based upon one specific biomarker may not be the right strategy. The transcriptional subtypes are showing promise in terms of therapeutic vulnerabilities, but how do we really put that into clinical practice? The question of heterogeneity and subtype switching comes up. I think it’s very important to try to develop biomarkers, and certainly we should be doing that as a field moving forward. I worry that it’s not going to be the same application in small cell as it is in non–small cell lung cancer.

References

1. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408
2. Tarlatamab with anti–PD-L1 as first-line maintenance after chemo-immunotherapy for ES-SCLC demonstrates acceptable safety profile and unprecedented overall survival. News release. IASLC. Accessed August 4, 2026. https://www.iaslc.org/iaslc-news/press-release/tarlatamab-anti-pd-l1-first-line-maintenance-after-chemo-immunotherapy-es
3. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. FDA. October 2, 2025. Accessed August 4, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive