Benjamin P. Levy, MD, is clinical director of Medical Oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital and associate professor of oncology at Johns Hopkins University School of Medicine.

Panelists discuss how the ADRIATIC regimen integrates immunotherapy post-chemoradiation in late-stage small cell lung cancer (LS-SCLC). In patients with paraneoplastic syndromes or immune disorders, immunotherapy requires caution. Prophylactic cranial irradiation (PCI) is considered for high-risk cases, while MRI surveillance is preferred for select patients to reduce neurotoxicity.

Expert Insights on Recent Advancements in LS-SCLC

Video content above is prompted by the following:

How are you incorporating the ADRIATIC regimen into your clinical practice?

What is the role of immunotherapy in patients with LS-SCLC and paraneoplastic syndromes or immune disorders, and how might you approach treatment in this patient subgroup?

What is the role of prophylactic cranial radiation in LS-SCLC? In which patients would you consider PCI vs MRI surveillance alone?

Videos

Dr Shields on Key ADRIATIC Trial Data With Adjuvant Durvalumab in LS-SCLC

“More studies are needed to understand this trend [in] improvement [with immunotherapy] in LS-SCLC vs ES-SCLC, [although data still demonstrate the benefit of] immunotherapy in both settings.”

Misty D. Shields, MD, PhD, assistant professor, clinical medicine, Department of Medicine, Division of Hematology/Oncology, Indiana University (IU) School of Medicine; and associate member, Experimental and Developmental Therapeutics, IU Melvin and Bren Simon Comprehensive Cancer Center, discusses the implications of the phase 3 ADRIATIC trial (NCT03703297) investigating adjuvant durvalumab (Imfinzi) vs placebo in patients with limited-stage small cell lung cancer (LS-SCLC).

The international, randomized ADRIATIC trial demonstrated that consolidation durvalumab administered every 4 weeks for a maximum of 2 years following concurrent platinum-based chemoradiotherapy significantly improved progression-free survival (HR, 0.76; 97.195% CI, 0.61-0.95; 

= .0161) and overall survival (HR, 0.73; 95% CI, 0.57-0.93; 

= .0104) compared with placebo in patients with LS-SCLC. Benefits with durvalumab were observed regardless of whether patients had received prophylactic cranial irradiation and irrespective of prior use of carboplatin and cisplatin, Shields says. However, greater improvements were noted in those who received carboplatin as chemosensitizing therapy during radiation, she explains. 

 and is established as the standard of care for the treatment of patients with LS-SCLC whose disease has not progressed after concurrent platinum-based chemoradiotherapy. Notably, the recommended dose of durvalumab is 1500 mg every 4 weeks for patients with a body weight of at least 30 kg and 20 mg/kg every 4 weeks for those with a body weight of less than 30 kg for a maximum of 24 months, or until disease progression or unacceptable toxicity.

However, the underlying mechanisms explaining why immunotherapy demonstrates greater efficacy in LS-SCLC compared with extensive-stage SCLC (ES-SCLC) remain unclear, Shields notes. This represents an unmet translational need, warranting further investigation, she emphasizes. Potential factors include its activity in specific neuroendocrine subtypes (such as inflamed subtypes), abscopal effects of immunotherapy following radiation, or increased neoantigen presentation, she states. Ultimately, though, immunotherapy continues to generate favorable outcomes in both LS-SCLC and ES-SCLC, Shields concludes.

Misty D. Shields, MD, PhD, discusses the implications of the ADRIATIC trial of adjuvant therapy with durvalumab vs placebo in patients with LS-SCLC.

Misty D. Shields, MD, PhD, discusses the FDA approval of tarlatamab for patients with extensive-stage small cell lung cancer.

Dr Shields on Incorporating Tarlatamab into Clinical Practice for ES-SCLC

Misty D. Shields, MD, PhD, assistant professor, Clinical Medicine, Department of Medicine, Division of Hematology/Oncology, IU School of Medicine; associate member, Experimental and Developmental Therapeutics, translational medical oncologist, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, discusses the significance of the FDA approval of tarlatamab-dlle (Imdelltra) for patients withextensive-stage small cell lung cancer (ES-SCLC), as well as highlights challenges associated with the incorporation of this agent into clinical practice. 

Shields begins by stating that the incorporation of the DLL3-targeted bispecific T-cell engager into the treatment arsenal for relapsed SCLC is one of the most striking updates in 2024. On May 16, 2024, 

the FDA granted accelerated approval to tarlatamab

 for patients with ES-SCLC who have experienced disease progression following platinum-based chemotherapy, she reports.

The regulatory decision was supported by data from the phase 2 DeLLphi-301 trial (NCT05060016), in which patients with relapsed/refractory ES-SCLC (n = 99) experienced an objective response rate (ORR) of 40% (95% CI, 31%-51%) and a median duration of response (DOR) of 9.7 months (range, 2.7 to 20.7+) with tarlatamab. This high response rate has generated considerable excitement and hope for improving outcomes in relapsed SCLC, a disease known for its aggressive nature and poor prognosis, Shields comments. However, the transition from clinical trials to widespread clinical implementation presents unique challenges, she says.

Operational and logistical barriers to implementing tarlatamab therapy are significant and will vary by institution and health system, Shields states. One of the primary concerns is the administration protocol, which requires that patients be observed in the hospital for a minimum of 22 to 24 hours during the first 2 treatment days of cycle 1, she explains. Each institution will need to develop and refine their standard operating procedures to accommodate this requirement, which could strain hospital resources and necessitate additional training for healthcare staff, Shields says.

Furthermore, ensuring equitable access to tarlatamab will be a challenge, Shields continues. The infrastructure and resources required to administer this therapy may not be uniformly available, potentially leading to disparities in patient care, she explains. Effective implementation will depend on each institution's ability to navigate these challenges, requiring close coordination and planning, Shields emphasizes.

More research is needed to confirm tarlatamab's efficacy and understand the biomarkers that predict responses with the agent, Shields adds. Determining the optimal patient selection and treatment sequencing is essential to maximize the therapeutic benefits and minimize unnecessary risks, she concludes.

Misty D. Shields, MD, PhD, assistant professor, clinical medicine, Department of Medicine, Division of Hematology/Oncology, associate member, Experimental and Developmental Therapeutics, Indiana University School of Medicine, discusses systemic therapy updates for patients with extensive-stage small cell lung cancer (ES-SCLC).

At the 2023 IASLC World Conference on Lung Cancer, Dr Shields presented the latest updates in upfront systemic therapy for patients with ES-SCLC. One important study discussed at this meeting was the IMbrella A trial, Shields says. IMbrella A was an observational extension study of the phase 3 IMpower133 trial (NCT02763579), which evaluated atezolizumab (Tecentriq) or placebo plus carboplatin and etoposide in patients with treatment-naïve ES-SCLC. Patients from the atezolizumab arm of IMpower133 were eligible for enrollment in IMbrella A if they continued to receive atezolizumab after the study’s closure or were in survival follow-up after IMpower133 closed. At a median follow-up of 59.4 months (range, 0.0-72.6), the median OS in the atezolizumab arm of IMpower133 was 12.3 months (95% CI, 10.8-15.8). The median OS in the placebo arm of this study was 10.3 months (95% CI, 9.3-11.3) at a median follow-up of 26.4 months (range, 0.0-34.4).

Additionally, the combined 5-year OS rate in the IMpower133 and IMbrella A atezolizumab cohort was 12% (95% CI, 7%-17%).

Findings from the phase 3 ETER701 trial (NCT04234607) were also reported at the meeting. This trial evaluated the PD-L1 inhibitor benmelstobart (TQB2450) plus anlotinib (AL3818) and carboplatin/etoposide vs anlotinib plus placebo and carboplatin/etoposide vs placebo plus carboplatin/etoposide in patients with previously untreated ES-SCLC, Shields explains. In this trial, patients in the benmelstobart arm achieved a median OS of 19.32 months (95% CI, 14.23-not evaluable) vs 11.89 months (95% CI, 10.74-13.37) for those in the placebo plus carboplatin/etoposide arm. Additionally, the median progression-free survival was 6.93 months (95% CI, 6.18-8.25) in the benmelstobart arm vs 4.21 months (95% CI, 4.17-4.24) in the placebo plus carboplatin/etoposide arm.

Misty D. Shields, MD, PhD, discusses systemic therapy updates for patients with extensive-stage small cell lung cancer.

Misty D. Shields, MD, PhD

Articles

Expert Insights on Recent Advancements in LS-SCLC

Dr Shields on Key ADRIATIC Trial Data With Adjuvant Durvalumab in LS-SCLC

Dr Shields on Incorporating Tarlatamab into Clinical Practice for ES-SCLC

Dr Shields on Updates in Upfront Systemic Therapy in ES-SCLC