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The National Comprehensive Cancer Network (NCCN) updated their Clinical Practice Guidelines in Oncology for the treatment of patients with small cell lung cancer (SCLC) to include new additions involving Lambert Eaton myasthenic syndrome (LEMS), amifampridine (Firdapse), and the tests for PQ- and N-type voltage-gated calcium channel (VGCC) antibodies.1,2
The revisions include symptom specificity for LEMS, defined by proximal muscle weakness and autonomic dysfunction. Additionally, the guidelines now recommend diagnosis through a neurological evaluation, preferably in conjunction with a neurologist, which may include testing for PQ- and N-type VGCC antibodies. Moreover, the guidelines state that amifampridine should be considered as a treatment in consultation with a neurologist. The latter two revisions can be found housed in the guidelines under “Signs and Symptoms of Small Cell Lung Cancer” (SCL-A 2 of 2) and “Principles of Supportive Care” (SCL-D), respectively.
“Early diagnosis of LEMS in SCLC is critical, as it may enable patients to have better outcomes if their LEMS symptoms are effectively treated while fighting SCLC.1 Accurate identification through VGCC antibody testing and comprehensive neurological evaluation is essential,” William Andrews, MD, FACP, chief medical officer of Catalyst stated in a news release. “The NCCN Guidelines are a trusted standard for guiding treatment decisions, and we believe this update will drive greater awareness. Ultimately, it will help patients, caregivers, and health care providers make more informed choices when addressing this serious unmet need.”
Approximately half of LEMS cases are tied to an underlying malignancy, and in most cases SCLC. Data suggest that LEMS occurs in 3% of patients with SCLC. An internal health case database from Catalyst of SCLC claims found that 90% of patients with LEMS and SCLC were undiagnosed with the former condition, bearing the brunt of SCLC treatment while experiencing disease-related symptoms.
Other Notable Guideline Updates
In terms of pathologic assessment, bullet 8 of section SCL-B 1 of 2 (“Principles of Pathologic Review”) was adjusted to remove the number of daily cigarettes as a threshold (<10 cigarettes/day). The update now states that comprehensive molecular profiling via blood, tissue, or both can be considered in rare cases, particularly for patients with extensive-stage or relapsed SCLC who do not smoke tobacco, lightly smoke, have remote smoking history, or have diagnostic or therapeutic dilemma, or at time of relapse—if not previously done, because this may change management.2
Regarding imaging, footnote e within section SCL-1 (“Initial Evaluation and Staging”) was amended, now stating that brain MRI is more sensitive than CT for identifying brain metastases and is preferred over CT.
With respect to treatment, under section SCL-E 1 of 6 (“Principles of Systemic Therapy”) the guidelines moved carboplatin at an area under the curve 5 or 6 on day 1 and etoposide 100 mg/m2 on days 1, 2, 3 from other recommended regimen to preferred as primary or adjuvant therapy for patients with limited stage disease.
Additionally, a fifth sub-bullet was added to section SCL-F 2 of 7 (“Principles of Radiation Therapy”), noting the significant survival benefit associated with adjuvant durvalumab (Imfinzi) in patients who have not progressed after the completion of chemoradiotherapy. The addition was added with the caveat that the optimal dose and schedule of radiation therapy in the context of immunotherapy is at present, undefined.
To read more about the NCCN’s guideline updates published throughout 2024, click here.
To learn more about LEMS, check out this OncLive Insights program, featuring David Gerber, MD, and Steven Vernino, MD, PhD.
References
- Lambert Eaton Myasthenic Syndrome (LEMS) Antibody Testing and Treatment Recommendations Added to NCCN Clinical Practice Guidelines for Small Cell Lung Cancer (SCLC). News release. Catalyst Pharmaceuticals, Inc. August 6, 2025. Accessed August 7, 2025. https://ir.catalystpharma.com/news-releases/news-release-details/lambert-eaton-myasthenic-syndrome-lems-antibody-testing-and
- NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 1.2026. Accessed August 7, 2025. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf