Response assessment of NovoTTF-100A versus best physician's choice chemotherapy in recurrent glioblastoma

Eric T. Wong (1) , Edwin Lok (1) , Kenneth D. Swanson (1) , Shiva Gautam (1) , Herbert H. Engelhard (2) , Frank Lieberman (3) , Sophie Taillibert (4) , Zvi Ram (5) , John L. Villano (6)

1 Beth Israel Deaconess Medical Center
2 UIC - University of Illinois [Chicago]
3 University of Pittsburgh School of Medicine
4 CHU Pitié-Salpêtrière [AP-HP]
5 Tel Aviv Sourasky Medical Center [Te Aviv]
6 UK - University of Kentucky

The NovoTTF-100A device emits frequency-tuned alternating electric fields that interfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less toxicity when compared to Best Physician's Choice (BPC) chemotherapy. We analyzed the characteristics of responders and nonresponders in both cohorts to determine the characteristics of response and potential predictive factors. Tumor response and progression were determined by Macdonald criteria. Time to response, response duration, progression-free survival (PFS) AE Simon–Makuch correction, overall survival (OS), prognostic factors, and relative hazard rates were compared between responders and nonresponders. Median response duration was 7.3 versus 5.6 months for NovoTTF-100A and BPC chemotherapy, respectively (P = 0.0009). Five of 14 NovoTTF-100A responders but none of seven BPC responders had prior low-grade histology. Mean cumulative dexamethasone dose was 35.9 mg for responders versus 485.6 mg for nonresponders in the NovoTTF-100A cohort (P < 0.0001). Hazard analysis showed delayed tumor progression in responders compared to nonresponders. Simon–Makuch-adjusted PFS was longer in responders than in nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P = 0.0222). Median OS was longer for responders than nonresponders treated with NovoTTF-100A (P < 0.0001) and BPC chemotherapy (P = 0.0235). Pearson analysis showed strong correlation between response and OS in NovoTTF-100A (P = 0.0002) but not in BPC cohort (P = 0.2900). Our results indicate that the response characteristics favor NovoTTF-100A and data on prior low-grade histology and dexamethasone suggest potential genetic and epigenetic determinants of NovoTTF-100A response.

Mots clés: NovoTTF-100A; recurrent glioblastoma; response

Domaines: Cancer

Eric T. Wong, Edwin Lok, Kenneth D. Swanson, Shiva Gautam, Herbert H. Engelhard, et al.. Response assessment of NovoTTF-100A versus best physician's choice chemotherapy in recurrent glioblastoma. Cancer Medicine, 2014, 3 (3), pp.592-602. ⟨10.1002/cam4.210⟩. ⟨hal-01311566⟩