NCCN Updates Small Cell Lung Cancer Guidelines With New LEMS Recommendations

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Small Cell Lung Cancer (SCLC) have been updated to include critical guidance on Lambert-Eaton Myasthenic Syndrome (LEMS). The revisions incorporate important LEMS updates, including recommendations on the use of amifampridine (Firdapse) and antibody testing for PQ- and N-type voltage-gated calcium channels (VGCC).¹

The updated guidelines now clearly define LEMS symptoms—notably proximal muscle weakness and autonomic dysfunction. In the section, “Signs and Symptoms of Small Cell Lung Cancer” (SCL-A 2 of 2),” it is recommended that the diagnostic evaluation involves a neurological assessment conducted with the consultation of a neurologist. Testing for PQ- and N-type VGCC antibodies may be included to aid diagnosis. In the “Principles of Supportive Care” (SCL-D) section, the guidelines advise considering amifampridine therapy, with neurology consultation, as part of comprehensive care for patients with LEMS.

LEMS is a rare disorder of the neuromuscular junction that can occur either as a paraneoplastic syndrome, most often in association with small cell lung cancer, or as a primary autoimmune condition. It is characterized primarily by progressive muscle weakness. The condition arises when antibodies target VGCCs on presynaptic nerve terminals, impairing calcium influx and thereby reducing the release of the neurotransmitter acetylcholine.²

“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. Accurate identification through VGCC antibody testing and comprehensive neurological evaluation is essential,” William Andrews, MD, FACP, chief medical officer, Catalyst Pharmaceuticals, stated in a press 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 healthcare providers make more informed choices when addressing this serious unmet need.”¹

FDA Approval for Amifampridine

Amifampridine, which is manufactured by Catalyst, is a potassium channel blocker that was approved by the FDA in 2018 for the treatment of adult and pediatric patients with LEMS. One of the key studies that led to the approval was a randomized, double-blind, placebo-controlled phase 3 discontinuation trial (NCT01377922) that included 38 patients with LEMS (median age 54 years; range, 21-88).³

After completing an open-label run-in phase, the study patients were randomized in a double-blind manner to either continue amifampridine (n = 16) or undergo a 7-day tapering down to placebo (n = 22). After this tapering period, participants remained on their assigned blinded treatment for an additional 7 days. Treatment efficacy was evaluated on day 14 of the double-blind phase.

The co-primary outcome measures for the study were change from baseline to the end of the discontinuation period in the physician-assessed Quantitative Myasthenia Gravis (QMG) score for muscle weakness and in the patient-assessed Subject Global Impression (SGI) score, which measures a patient’s assessment of a treatment’s efficacy on their physical well-being. Higher scores on the QMG correlate with greater impairment, whereas lower scores on the SGI indicate a lower perception of the efficacy of the study treatment.

During the double blind-period from baseline to day 14, both the QMG scores SGI scores mostly worsened in both randomized arms; however, there was a significantly greater worsening in the placebo arm vs the amifampridine arm for both the QMG (P \ .045) and SGI (P =.003) assessments.³

Amifampridine is currently the only FDA-approved therapy that is specifically for the treatment of patients with LEMS.

REFERENCES:

1. 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. August 6, 2025. Accessed August 8, 2025. https://tinyurl.com/4ebrdwh2

2. Jayarangaiah A, Lui F, Kariyanna PT. Lambert‑Eaton Myasthenic Syndrome. StatPearls. Published online October 23, 2023. Accessed August 8, 2025. https://www.ncbi.nlm.nih.gov/books/NBK507891

3. Catalyst Pharmaceuticals, Inc. FIRDAPSE (amifampridine) tablets: Highlights of Prescribing Information. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.; 2024. Accessed August 8, 2025. https://firdapsehcp.com/pdfs/firdapse-