Other / General Medicine
Haylee Yepson, DO
Resident Physician
University of Colorado
Denver, Colorado, United States
Franchesca Konig, MD
DIRECTOR, CANCER REHABILITATION
University of Colorado
Aurora, Colorado, United States
Tejas Patil, MD
Assistant Professor
University of Colorado
Aurora, Colorado, United States
Haylee Yepson, DO
Resident Physician
University of Colorado
Denver, Colorado, United States
Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for certain Epidermal Growth Factor Receptor (EGFR) positive non-small cell lung cancers (NSCLC). This study aims to identify lower extremity nocturnal cramping as a distinct, previously unreported treatment-related adverse event (TRAE) of osimertinib and provide therapeutic recommendations.
Design:
This case series reviews nine patients with EGFR-mutant NSCLC who developed leg cramping after starting osimertinib. Charts were reviewed for demographics, symptoms, functional impact, laboratory data, treatment and outcomes. Descriptive statistics were calculated.
Results:
Mean age at osimertinib initiation was 57.4 years, and all patients were female. Symptom onset occurred at a mean of 207.25 ± 162.32 days. All patients experienced lower extremity cramping; 66.6% had primarily nocturnal symptoms. Two patients experienced functional limitations, one required temporary discontinuation and dose adjustment. Creatine kinase and magnesium were measured in 77.7% and 100% of patients and were all within normal ranges. Management strategies included vitamin and electrolyte supplementation and physical modalities. Medications trialed included gabapentin, muscle relaxants, duloxetine, pramipexole, and lorazepam. Symptom control often required multimodal approach with 22.2%, 44.4%, and 22.2% requiring two, three, and four treatment modalities, respectively. No cases had documented symptom resolution, though 33.3% of patients showed improvement.
Conclusions:
Muscle cramps were not reported as TRAEs in osimertinib’s registration studies. In our cohort, nocturnal cramps appeared distinct from previously described myalgia or rhabdomyolysis and may arise anytime during treatment. This under recognized adverse event can affect quality of life, function, and treatment adherence. Physiatrists are essential in crafting multimodal plans with oncology teams. Initial treatments may include magnesium , B-complex, stretching, and neuropathic pain medications. Notably, 22.2% of patients tried tonic water, despite FDA warnings due its quinine content. No large studies yet define the prevalence, impact, or safe effective treatments for osimertinib-related nocturnal leg cramps—underscoring the need for further research.
