The Study: The German phase 3 NOA-09 trial randomized 141 patients ≤70 years with newly-diagnosed MGMT-methylated GBM to adjuvant conventionally-fractionated radiation with standard concurrent and maintenance temozolomide (TMZ) +/- lomustine. In arm  TMZ was dosed 75 mg / m2 daily x 42 days during radiation then maintenance 150-200 mg / m2 on days 1-5 of a 28-day cycle x 6. In arm  combo lomustine 100 mg / m2 was delivered on day 1 + TMZ 150-200 mg / m2 on days 2-6 of a 42-day cycle x 6 starting day 1 of radiation. Better yet, just look at figure 1. The primary endpoint of median overall survival (from time of randomization) was assessed among the cohort receiving at least the first cycle of chemo (n=129), and it was significantly improved from 31 to 48 months with the addition of lomustine. Whoa. These survival times are roughly twice that achieved in the standard and experimental arms of the landmark EF-14 trial. That’s with the major caveat these patients are exclusively MGMT-methylated versus only 41% of the EF-14 population. However, even among this specific subset in EF-14, median survival (from time of completion of chemoradiation) was roughly 18 versus 30 months without and with the addition of tumor-treating fields.
Bottom Line: The addition of lomustine to concurrent and maintenance TMZ with upfront adjuvant radiation for MGMT-methylated GBM results in unprecedented survival times. | Herrlinger, Lancet 2019