Correspondence
Using Choi criteria, the decreased tumour density under regorafenib might demonstrate the drug efficacy. Conversely, progression occurring at the rim of the tumour (or inside the tumour) might not be recognised by RECIST, and lead to unnecessary maintenance of regorafenib. These concerns led to the development of Choi and modified RECIST 1.1 criteria that could be retrospectively assessed in the CORRECT and GRID trials to provide physicians with appropriated tools to measure drug activity in routine practice.2,6 ER and TA have received honoraria from Bayer. AdG declares that he has no conflicts of interest.
*Thierry André, Eric Raymond, Aimery de Gramont
[email protected] Hôpital Saint-Antoine, 75012 Paris, France (TA, AdG); and Hôpital Beaujon, Clichy, France (ER) 1
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Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303–12. Demetri GD, Reichardt P, Kang YK, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 295–302. Mross K, Frost A, Steinbild S, et al. A phase I dose-escalation study of regorafenib (BAY 734506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012; 18: 2658–67. Strumberg D, Scheulen ME, Schultheis B, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer 2012; 106: 1722–27. George S, Wang Q, Heinrich MC, et al. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol 2012; 30: 2401–07. Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007; 25: 1753–59.
might not be enough to support the cost-effectiveness of regorafenib.2 Therefore, as stated by the authors,1 the search of markers of clinical benefit is important for future development. Regorafenib multikinase spectrum of inhibition, is unlikely to be linked to a mechanistic molecular biomarker presently assessable.3 We reasoned that some radiological tumour changes noticed with agents such as bevacizumab,4 but previously unreported with regorafenib, could represent imaging markers of clinical outcome. We analysed retrospectively 37 patients with mCRC enrolled at our institution in the CORRECT trial (22 received regorafenib, 15 received placebo, and overall 98 target lesions). Regorafenib induced changes of radiological tumour density as well as cavitation of lung metastases. The latter occurred among patients with lung involvement (eight of ten receiving regorafenib vs zero of 12 receiving placebo; Fisher exact twotailed: p
