Expanding Treatment Arsenal Renews Hope for Improved Outcomes in Limited and Extensive SCLC

Isabel Preeshagul, DO, MBS

Recent developments in the management of small cell lung cancer (SCLC), including data supporting the use of durvalumab (Imfinzi) following concurrent upfront chemotherapy in limited-stage disease (LS-SCLC) and the FDA approval of tarlatamab-dlle (Imdelltra) for patients with extensive-stage disease (ES-SCLC), are making strides towards addressing the urgent need for expanded treatment options in both settings, according to Isabel Preeshagul, DO, MBS.

In an interview with OncLive®, Preeshagul noted that the phase 3 ADRIATIC trial (NCT03703297) data on durvalumab are “practice changing for most of us, myself included, and we are excited to have something else to offer these patients.” Durvalumab given as primary or adjuvant therapy is now recommended by the NCCN as a preferred regimen for the treatment of patients with LS-SCLC.¹

Preeshagul highlighted how data on durvalumab following concurrent chemoradiation have generated considerable excitement and hope for improving outcomes in LS-SCLC, discussed expanded second-line treatment options in ES-SCLC, and detailed lingering uncertainties regarding patient selection and treatment sequencing after progression on frontline regimens in the interview.

In a concurrent interview, Preeshagul expanded on updated data informing treatment strategies for patients with EGFR-mutant non–small cell lung cancer, as well as ongoing topics of debate regarding the use of neoadjuvant vs adjuvant approaches. Preeshagul is a thoracic medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in Montvale, New Jersey.

OncLive: How have data on the use of durvalumab following concurrent chemoradiation impacted patient outcomes and treatment expectations in LS-SCLC?

Preeshagul: The ADRIATIC trial evaluated the role of durvalumab following concurrent chemotherapy and radiation for patients with LS-SCLC. These data are exciting because they [may support] a new approval in this space. We have had no new approvals in LS-SCLC for decades. Finally, we [may] have something in this space. It was like a light shined in an area that had not had much activity in way too long. [In this study], we found that the addition of durvalumab for [up to] 2 years following concurrent chemotherapy and radiation not only improved progression-free survival [PFS] by 7.4 months, but overall survival by 22.5 months.

Typically, patients with LS-NSCLC would get concurrent chemotherapy and radiation, and that was it. We would [consider] prophylactic cranial radiation for them, but they were [just] getting their scans every 3 months per NCCN guidelines—patients were waiting for the other shoe to drop and were appropriately anxious. Now we’re telling them that we have something else we can offer them, that can extend their survival [as well as] the time that they have before the cancer could potentially come back. It’s really exciting.

How have treatment options expanded in the second line setting and beyond for ES-SCLC?

ES-SCLC has become the poster child for [progress in SCLC] as of late. We had the FDA approval of lurbinectedin [Zepzelca] a couple of years ago, and more recently we had the approval of tarlatamab, which is a bispecific T-cell engager. Both drugs are approved after progression on platinum-etoposide plus immunotherapy. Tarlatamab is approved in the second line and beyond. From my perspective [as a clinician] it’s fairly well tolerated, but I can’t speak to the patient [experience] as truthfully as I would like to.

But from the data, it seems to be fairly well tolerated outside of cytokine release syndrome [CRS], which tends to be the main toxicity that we worry about. That tends to happen within the first cycle. For the first cycle, we usually split the dose and administer the agent in a hospital setting to monitor for the occurrence of CRS. If this doesn’t happen within the first cycle or 2, it typically does not occur. Outside of cytopenias and other adverse effects that we worry about with tarlatamab, once you pass that initial threshold, it tends to be well tolerated. [Regarding efficacy,] we’re looking at a response rate of 40% and a median PFS of 4.9 months.

What questions remain about the optimal use of these newer agents in ES-SCLC?

Overall, tarlatamab is a good option for my clinical practice. [However, in addition to] these 2 options, we also have topotecan, irinotecan, and temozolomide and a taxane [FDA approved] in this space. My main question is: How do we know what the right [treatment option] is in the second line setting for patients with ES-SCLC? I don’t think we know that answer.

Another question that I have is: Should we be including antibody-drug conjugates [ADCs] in this space? We know there are over 300 in development right now, and they’re creeping into the SCLC space, so maybe there’s a role for combining [approved agents] with ADCs. I’m still [figuring out the best way to proceed] when patients progress on frontline chemoimmunotherapy in the extensive-stage setting, but I’m grateful that we now have options.

Reference

1. NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 2.2025. Accessed October 7, 2024. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf