The ketogenic diet plus standard of care for adults with recently diagnosed glioblastoma: Results from a phase 1 trial.

Abstract

2076 Background: Facing limited treatment options, brain tumor patients are often highly motivated to use complementary therapies, including diet, to help themselves. There is now an abundance of preclinical evidence suggesting possible benefit with a ketogenic diet (KD) for brain tumor patients, but clinical evidence is still limited. Thus, we conducted a single-arm, phase 1 safety and feasibility trial of a KD among patients with recently diagnosed glioblastoma (GBM) during standard- of-care (SOC) treatment. Methods: Adults with GBM within 3 months of diagnosis followed a supervised 16-week diet intervention of a standard 3:1 KD (Fat(g):Carbohydrate+Protein(g)) plus SOC chemoradiation. Primary outcome was safety, evaluated by weekly assessments of weight and body mass index (BMI). Secondary outcomes included feasibility (pre-specified as > 50% of patients maintaining blood ketone levels > 0.3 mM over 50% of study days), progression-free survival (PFS), overall survival (OS), health-related quality-of-life (QOL), and cognitive function. Twice daily blood glucose and ketone levels, weight/BMI, physical activity, and sleep were assessed by remote monitoring. Results: Seventeen patients were evaluable: 53% women, median age 55, median Karnofsky Performance Status 85. All participants met the primary safety objective with no instances of excessive weight loss or related serious adverse events. Adherence to KD was high: all 17 patients maintained nutritional ketosis (≥0.3 mM/dL) >50% of study days, where 14 patients maintained nutritional ketosis >85% of study days. Median time to ketosis from diet initiation was 3 days. Diet-related AEs were mild and manageable; no patients came off study due to inability to tolerate KD. Median progression-free survival (PFS) and overall survival (OS) were 12.5 months and 28.6 months from KD initiation respectively. QOL, symptom control, and cognitive function remained stable or improved, although these did not reach statistical significance. Conclusions: This phase 1 trial demonstrates that KD is safe and feasible for GBM patients receiving SOC, may improve outcomes, and provides a foundation for future randomized trials to assess efficacy. Clinical trial information: NCT03451799 .