Survival outcomes of patients who develop new lesions while participating on phase I oncology studies.
Authors: R. K. Jain, J. Lee, C. S. Ng, D. S. Hong, J. Gong, A. Naing, J. Wheler, R. Kurzrock
Journal: Journal of Clinical Oncology (2010)

e13076 Background: Clinical trials of anticancer treatments commonly employ the Response Evaluation Criteria in Solid Tumors (RECIST), by which any patient with a newly discovered lesion is defined as having progressive disease (PD). This has important implications for patients and for the development of new treatments given these patients are almost always discontinued from the trial medication. However, the commonly held assumption that development of new sites of disease translates into poor outcomes is not well studied. Methods: Our dataset included 570 patients on 24 consecutive phase I trials of systemic therapy at MD Anderson between 10-01-04 and 6-30-08 who underwent at least one re-imaging study after initiation of phase I study treatment. Kaplan-Meier estimates of overall survival (OS) were calculated for patients binned by response as defined by RECIST. Survival estimates were compared using the log-rank test. Landmark analyses were performed to address the issue of comparing survival between response groups. Results: Of 570 patients, 102 had at least one new lesion at re-imaging and were therefore classified as having PD and taken off study. These patients had a median OS of 5.3 months. This was similar to the patients who had a best response of PD based on a quantifiable change of ≥20% increase in tumor size but without any new lesions (n = 152, median OS = 6.5 months; p = 0.10). In comparison, patients with a best response of stable disease (SD) had median OS of 14.1 months (n = 291; p < 1x10−6 when compared to patients with PD because of new lesions), and patients with a best response of partial or complete response (PR or CR) had OS = 2.7 years (n = 25; p < 1x10−6 when compared to patients with PD because of new lesions). Landmark analyses at three months, six months, and one year demonstrated identical trends. Conclusions: These data support the currently employed practice of removing patients from phase I oncology studies when re-imaging after initiation of therapy reveals the appearance of new lesions. Analysis is ongoing to determine if outcome is influenced by the number of new lesions, and/or when regression is observed in some lesions in patients who still develop other new lesions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Centocor Ortho Biotech, Johnson & Johnson, Maxygen, Merck Amgen, AstraZeneca, Enzon, Genentech, IDSC, ImClone Systems, Johnson & Johnson, Maxygen, Merck, Pharmion, Roche Abraxis BioScience, Amgen, AmpliMed, Antigenics, AstraZeneca, Bayer, Bristol-Myers Squibb, Callisto Pharmaceuticals, Centocor Ortho Biotech, Concordia, Curagen, Eisai, Enzon, Exelixis, Genentech, GlaxoSmithKline, Globomax, Kinex, Lilly, Merck, Metastatix, MGI Pharma, Myriad, Nereus, Novartis, Pfizer, Pharmacyclics, Pharmion, Phoenix Biotech, Reata, Roche, Taiho Pharmaceutical, Vioquest, Ziopharm