Go, no-go decision making for phase 3 clinical trials: ACT IV revisited – Authors' reply

[...]an important lesson learned from ACT IV is that even carefully assembled historical controls can be misleading and an unsuitable basis for clinical trial designs. Obtaining contemporary outcome data to standard therapies is challenging and remains an important issue, especially with the increasing trend for seamless oncology drug development and acceleration of drug development timelines.4,5 MW reports grants and personal fees from Roche, Merck, Actelion, and Novocure; personal fees from MSD, Pfizer, Tocagen, Celldex, Magforce, Bristol-Myers Squibb; and grants from OGD2, Acceleron, and Bayer, outside the submitted work. NB, LDR, HH, LA, LM, JD, and JP declare no competing interests. 1 M Weller, N Butowski, DD Tran, Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial, Lancet Oncol, Vol. 18, 2017, 1373-1385 2 MJ van den Bent, Y Gao, M Kerkhof, Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas, Neuro Oncol, Vol. 17, 2015, 935-941 3 J Felsberg, B Hentschel, K Kaulich, for the German Glioma Network, Epidermal growth factor receptor variant III (EGFRvIII) positivity in EGFR-amplified glioblastomas: prognostic role and comparison between primary and recurrent tumors, Clin Cancer Res, 2017, published online Aug 29.