Progression-Free Survival (Pfs) As A New Endpoint For Designing Phase Ii Trials In Patients With Refractory Germ Cell Tumors (Gct).

4583 Background: Refractory GCT patients have a poor prognosis and limited treatment options. Identification of novel active agents is a priority but may be impaired by use of response as the main endpoint in phase II trials. Improved endpoints may hasten the development of new effective agents. Methods: We retrospectively reviewed the characteristics and outcome of refractory GCT patients enrolled in 7 single-agent phase II trials conducted at MSKCC between 1990 and 2008. Study agents included: suramin, all- transretinoic acid, topotecan, pyrazoloacridine, temozolamide, ixabepilone, and sunitinib. For patients treated on more than 1 study, baseline characteristics and outcome to the first trial therapy were used. The major endpoints evaluated were response, PFS, and overall survival (OS). Results: 90 patients (M:F 87:3) were treated, including 4 patients enrolled on more than 1 study. The median age was 35 (range 17-64) and primary tumor site was testis in 65, mediastinum in 17, retroperitoneum in 4, and other in 4. 86 patients had non-seminoma and 4 had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95%CI: 0.8-1.3) and 4.7 months (95%CI: 3.5-6.4), respectively. 86 patients died; of the remaining 4 patients, 1 was rendered disease-free by salvage resection of a lung nodule, 1 achieved a durable complete response to single agent paclitaxel, and the other 2 have been lost to follow-up. The 12- and 16-week PFS rates were 9% and 6% respectively. Conclusions: Patients with refractory GCT progress rapidly when treated with ineffective agents. PFS may be a useful endpoint for designing phase II trials testing novel agents in this population. A 12-week PFS endpoint (with comparison to the 9% benchmark rate reported herein) is recommended. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Lilly, Pfizer Bristol-Myers Squibb, Genentech, Lilly, Pfizer