Tumor treating fields (TTFields) in combination with lomustine (CCNU) in the EF-14 phase 3 clinical study – a safety analysis

Introduction:

TTFields are low intensity (1-3V/cm), intermediate frequency (100-300 KHz) alternating electrical fields for the treatment of solid tumors. In the EF-14 phase 3 study, TTFields showed a significant overall and progression-free survival benefit for patients with newly diagnosed glioblastoma (GBM), in combination with Temozolomide (TMZ) (OS from randomization 20.9 vs. 16.0 months, p-value<0.001). The OS and PFS benefit of TTFields was seen in all patient subgroups, and was independent of MGMT promotor methylation-status, age, performance status and gender. TTFields were not associated with additional systemic toxicity. At recurrence, patients were allowed to continue TTFields with second line therapies. Here, we analyzed the safety data of TTFields + lomustine (CCNU) to evaluate the safety and feasibility of this combination.

Methods:

Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed in both groups after tumor progression. We compared the patients who received lomustine as second-line chemotherapy in combination with TTFields (n=134) to the patients who received lomustine as monotherapy after first progression (n=39). We compared baseline characteristics and the adverse event profile between the two groups.

Results:

Baseline characteristics were well balanced between both groups except for less female patients in the lomustine only group (7.7% vs. 22.4%). Median age in the TTFields/lomustine group was 55.5 years (29-83) compared to 50.0 years (19-71) for lomustine alone. The addition of TTFields to lomustine therapy was not associated with any significant increase in rates of systemic adverse events compared to lomustine therapy alone (number of patients with > 1 SAE 30 % vs. 31 %) and the distribution, severity and overall incidence of adverse events were not statistically different in patients in the two treatment groups.

Discussion:

The data show that the combination of TTFields and lomustine is a safe and feasible combination. This analysis emphasizes again the strong safety profile of TTFields and the high potential of combining TTFields with other therapy modalities. These data are especially important in light of the recently presented promising data from a small randomized trial that tested the combination of lomustine + TMZ in newly diagnosed (MGMT promotor-methylated only) GBM patients.