The Era of Precision Medicine: Advancing Treatment Paradigms for Small Cell Lung Cancer
Simple Summary
Abstract
1. Introduction
2. Chemotherapy
2.1. First-Line Chemotherapy
2.2. Maintenance Therapy
2.3. Second-Line Therapy and Beyond
3. Radiation Therapy
3.1. LS-SCLC
3.2. ES-SCLC
3.3. Emerging Modalities in RT
4. Immunotherapy
4.1. Immune Checkpoint Inhibitors
4.2. Oncolytic Viruses
5. Targeted Therapy
6. Bispecific Antibodies
6.1. Bispecific Antibody Structure
6.2. Use in Small Cell Lung Cancer
6.3. DLL3-Targeted
6.4. LAG-3-Targeted
6.5. GD2-Targeted
7. Antibody–Drug Conjugates
7.1. DLL3
7.2. Trophoblastic Cell Surface Antigen (TROP2)
7.3. B7-H3
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Trial Identifier/Authors | Treatment Modality | Clinical Setting | Treatment Setting | Outcome(s) |
---|---|---|---|---|
NCT02763579/Horn et al. [22] | Atezolizumab plus carboplatin and etoposide | Patients with ES-SCLC with previous treatment failure | 1200 mg atezolizumab on day 1 of each 21 day cycle for 4 cycles, followed by atezolizumab until toxicity or progression | Atezolizumab plus chemotherapy achieved a median PFS of 12.3 months compared to 10.9 months in the chemotherapy plus placebo |
NCT03043872/Paz-Ares et al. [23] | Durvalumab with or without tremelimumab in combination with EP | Patients with untreated ES-SCLC | 1500 mg durvalumab with or without tremelimumab 75 mg EP every 3 weeks for 4 cycles followed by 1500 mg durvalumab | Durvalumab plus chemotherapy achieved a median OS of 13.0 months versus 10.3 months in the chemotherapy group |
NCT01331525/Arriola et al. [75] | Ipilimumab plus carboplatin and etoposide | Chemotherapy naïve ES-SCLC | 10 mg/kg ipilimumab day 1 of chemotherapy cycles 3 and 6, then once every 12 weeks after week 30 | Ipilimumab had an objective response rate of 84.8% and a median immune-related progression free survival of 7.3 months |
NCT00527735/Reck et al. [76] | Ipilimumab plus paclitaxel and carboplatin (PC) | Chemotherapy naïve ES-SCLC | Phased or concurrent 10 mg/kg ipilimumab with PC every 3 weeks for 18 weeks, followed by ipilimumab every 12 weeks | Phased ipilimumab had an OS of 12.9 months vs. control of 9.9 months. Concurrent ipilimumab had a median OS of 9.1 months |
NCT01450761/Reck et al. [77] | Ipilimumab plus EP | Patients with ES-SCLC | 10 mg/kg ipilimumab with EP every three weeks for four cycles | Ipilimumab plus chemotherapy had a median OS of 11.0 months compared to 10.9 months in control group |
NCT03703297/ Cheng et al. [80] | Durvalumab plus tremelimumab vs. placebo | LS-SCLC that displayed resistance to chemoradiotherapy | 1500 mg durvalumab plus 75 mg tremelimumab or placebo every four weeks for 24 months | Durvalumab plus tremelimumab had a median OS of 55.5 months vs. 33.4 months in placebo |
NCT01928394/Ready et al. [81] | Nivolumab monotherapy | LS-SCLC and ES-SCLC with disease progression who failed two or more chemotherapy regimens | 3 mg/kg nivolumab every two weeks until disease progression or unacceptable toxicity | Nivolumab monotherapy achieved an 11.9% objective response rate and a median duration of response of 17.9 months |
NCT02054806/NCT02628067/Chung et al. [82] | Pembrolizumab monotherapy | Recurrent or metastatic SCLC who failed two or more previous treatment methods | 10 mg/kg pembrolizumab every 2 weeks or 200 mg every 3 weeks for up to 2 years | Pembrolizumab monotherapy achieved a 19.3% objective response rate with two patients achieving a complete response |
NCT03066778/Rudin et al. [84] | Pembrolizumab plus EP | Stage IV SCLC not previously treated with systemic therapy | 200 mg pembrolizumab once every 3 weeks for up to 35 cycles with 4 cycles of EP | 12-month PFS estimates in pembrolizumab plus EP was 13.6% vs. 3.1% in control plus EP |
Clinical Trial Identifier/Authors | Treatment Modality | Clinical Setting | Treatment Setting | Outcome(s) |
---|---|---|---|---|
NCT01286987/Bono et al. [114] | Talazoparib based monotherapy | Recurrent SCLC patients | Administered 1.0 mg talazoparib daily. | Talazoparib gave SCLC patients with BRCA mutations the highest objective response rate of 40%. 9% of patients had a partial response for 3–4 months. |
NCT03009682/Park et al. [115] | Olaparib based monotherapy | Patients who failed prior platinum-based regimen with mutations harboring homologous recombination pathway gene mutation | Olaparib 300 mg twice a day every 12 h administered daily. | Olaparin monotherapy gave an objective response rate of 6.7%. Disease control rate was 26.7%. Median progression-free survival was 1.25 months and median overall survival was 8.56 months. |
NCT03516084/Ai et al. [116] | Niraparib based monotherapy | Patients with complete response or partial response to standardized, platinum-based first-line chemotherapy | 300 mg niraparib if baseline body weight ≥ 77 kg or platelet count ≥ 150,000/μL. Otherwise, 200 mg niraparib once daily until progression or unacceptable toxicity. | Median progression free survival was 1.54 months. Median overall survival was 9.92 months. |
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Corica, D.A.; Bell, S.D.; Zhao, L.; Lawler, N.J.; Poirier, M.A.; Miller, P.J.; Wakefield, M.R.; Fang, Y. The Era of Precision Medicine: Advancing Treatment Paradigms for Small Cell Lung Cancer. Cancers 2025, 17, 1847. https://doi.org/10.3390/cancers17111847
Corica DA, Bell SD, Zhao L, Lawler NJ, Poirier MA, Miller PJ, Wakefield MR, Fang Y. The Era of Precision Medicine: Advancing Treatment Paradigms for Small Cell Lung Cancer. Cancers. 2025; 17(11):1847. https://doi.org/10.3390/cancers17111847
Chicago/Turabian StyleCorica, Derek A., Scott D. Bell, Lei Zhao, Nicholas J. Lawler, McKade A. Poirier, Peyton J. Miller, Mark R. Wakefield, and Yujiang Fang. 2025. "The Era of Precision Medicine: Advancing Treatment Paradigms for Small Cell Lung Cancer" Cancers 17, no. 11: 1847. https://doi.org/10.3390/cancers17111847
APA StyleCorica, D. A., Bell, S. D., Zhao, L., Lawler, N. J., Poirier, M. A., Miller, P. J., Wakefield, M. R., & Fang, Y. (2025). The Era of Precision Medicine: Advancing Treatment Paradigms for Small Cell Lung Cancer. Cancers, 17(11), 1847. https://doi.org/10.3390/cancers17111847