Abstract A70: Clinical outcomes and survival of advanced renal cancer patients in Phase I clinical trials.

Introduction: The main purpose of this study was to describe the basic demographics and to analyze the response and survival experience of advanced renal cancer subjects treated in a Phase I trial. Methods: We conducted a retrospective observational study in 70 advanced renal cancer patients who participated in 25 Phase I trials at the Institute for Drug Development, Cancer Therapy and Research Center, San Antonio between 2002 and 2012. All patients with advanced renal cell cancer of any histological subtype, beginning their first Phase I trial were included. Descriptive statistics, Kaplan Meier analyses, and multivariate Cox proportional hazards analyses were used to examine patient and clinical factors associated with 1) time from study entry to treatment failure and 2) survival after study entry. Results: The median age at diagnosis was 56 years (range 44-76). The most common histological types were clear cell (68%), mixed (11.5%), papillary (10%), and Sarcomatoid (7.2%). Twenty-three percent of the patients had an ECOG performance status of zero; 49% of patients had received ≥2 prior lines of systemic therapy including interleukin 2, tyrosine kinase inhibitors, bevacizumab, and chemotherapy. Prior nephrectomy rate was 94%. Eighty-four percent of patients had ≥2 metastatic sites; 31% had lung only, 8.5% had lymph node only, and 17% had liver only. A median number of 4 cycles of study treatment was delivered (range 1-28). The study was discontinued due to disease progression (78%), toxicity (10%), and non-medical reasons (11%). Twenty-five percent of patients enrolled into another Phase I study upon progression. No treatment related death was observed. Of the 64 evaluable patients, four partial responses (6.2%) and 28 cases of stable disease lasting >4 months (43.7%) were observed. Twenty-two patients (34.3%) had disease progression at the time of first tumor assessment. The median time to treatment failure (TTF) as measured from the start of therapy until disease progression or removal from study was 16 weeks. Kaplan Meier analyses demonstrated that patients who achieved a partial response had longer TTF as compared to subjects with stable disease. In multivariate analyses, males and patients with LDH >1.5 ULN had a shorter time to treatment failure. The median overall survival measured from the time of enrollment in the first Phase I trial to death was 45.5 weeks (319 days). In multivariate analysis, factors predicting shorter survival were baseline ECOG ≥1 (P=0.023), albumin <3.4 g/dl (P=0.042), and liver metastases (P=0.01). Conclusion: This analysis highlights the potential effectiveness of new therapeutic agents currently in development. It provides evidence that a significant proportion of patients with advanced renal cancer derive benefit from treatment in the phase I trials. Absence of liver metastases, good performance status, and normal serum albumin level were independently predictive of better survival. Use of tumor profiling and better patient selection as a routine part of cancer drug development could further improve the results. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A70. Citation Format: Laeeq Malik, Helen Parsons, Devalingam Mahalingam, Benjamin Ehler, Martin Goros, Andrew Brenner, John Sarantopoulos. Clinical outcomes and survival of advanced renal cancer patients in Phase I clinical trials. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A70.