RAF plus EGFR Inhibition for BRAF-Mutant Metastatic Colorectal Cancer—Response

We reported that 2 patients achieved partial responses, 8 patients achieved stable disease, and 2 patients had progression of disease by formal RECIST criteria. The RECIST measurements are graphically illustrated in the waterfall plot in Fig. 3 of our article (1). As shown in this figure, none of the patients who experienced “stable disease,” as defined by RECIST, actually had growth of their tumor on imaging studies, but rather had varied degrees of tumor shrinkage; in fact, 6 patients in the study had RECIST minor responses (10%–30% tumor shrinkage). Because the formal definition of “stable disease” is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease (2), the term can describe situations in which tumors actually never regressed, and in fact grew, but simply by less than 20% at the time of first imaging. Such was not the case in our study, however. We used the word “regression” in the abstract to describe this shrinkage, and its definition is the plain English one. Clinically, tumor regression is a meaningful sign of drug activity. As noted in a study by Le Cesne and colleagues (3), the absence of progression as assessed by RECIST can predict for survival to targeted therapies, as they find that regression on RECIST measurements enables early discrimination between patients who benefited from long-term imatinib and those who did not.See the original Letter to the Editor, p. 2187R. Yaeger reports receiving commercial research support from Genentech and Novartis and is consultant/advisory board member for Amgen. L.B. Saltz is a consultant/advisory board member for Lilly, Roche, Sanofi, and Taiho.