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Lung Cancer

Emerging Strategies for the Treatment of Small Cell Lung CancerA Review

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JAMA Oncology
Published Online: December 15, 2022
Review
W. Jeffrey Petty, MD1;
Luis Paz-Ares, MD2,3,4
Author Affiliations
  • 1Department of Internal Medicine, Section of Hematology and Oncology, Comprehensive Cancer Center of Wake Forest University, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 2Hospital Universitario 12 de Octubre, Madrid, Spain
  • 3H120-CNIO Lung Cancer Unit, Madrid, Spain
  • 4Universidad Complutense de Madrid and Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain
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Abstract

Importance  Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking.

Observations  This review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined.

Conclusions and Relevance  Therapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.

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Lung Cancer Targeted and Immune Cancer Therapy Oncology
Article Information

Accepted for Publication: September 12, 2022.

Published Online: December 15, 2022. doi:10.1001/jamaoncol.2022.5631

Corresponding Author: Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Av De Córdoba SN, 28041 Madrid, Spain (lpazaresr@seom.org).

Author Contributions: Drs Petty and Paz-Ares had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Paz-Ares.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Both authors.

Critical revision of the manuscript for important intellectual content: Paz-Ares.

Administrative, technical, or material support: Both authors.

Supervision: Both authors.

Conflict of Interest Disclosures: Dr Petty reported receiving nonfinancial support from Cello Health Communications during the conduct of the study; serving on advisory boards for Jazz Pharmaceuticals and Mirati outside the submitted work; being a consultant and advisor for Jazz Pharmaceuticals; and receiving institutional support for contracted research from Merck, Amgen, AstraZeneca, Pfizer, and AbbVie. Dr Paz-Ares reported receiving personal fees for consulting from AstraZeneca, Pfizer, Bristol Myers Squibb, Roche, MSD, Eli Lilly & Company, Pharmamar, Ipsen, Guardant, Merck, Amgen Scientific, Mirati, Bayer, and Novartis; receiving speaker honoraria from AstraZeneca, BMS, Roche, MSD, and Eli Lilly & Company; receiving grants from Pfizer, Bristol Myers Squibb, AZ, and Pharmamar; receiving speaker honoraria from Novartis outside the submitted work; being an external board member for Genomina; and being a cofounder and board member of Altum Sequencing.

Additional Contributions: Danyang Zhou, PharmD, and Sarah Thornburg, MS (Lumanity Scientific Inc), provided medical writing and editorial assistance and were financially supported by Jazz Pharmaceuticals.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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