Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre.

Background Greater understanding of the molecular classification of breast cancer has permitted the development of rational drug design strategies. In a phase I clinical trial setting, molecular profiling with next-generation sequencing of individual tumour samples has been employed to guide treatment.Methods We conducted a retrospective evaluation of clinical outcomes of patients with metastatic breast cancer (MBC) treated in phase I clinical trials at our institution to assess the benefit of molecularly matched compared to non-matched treatments.Results A total of 97 consecutive patients with MBC were enrolled onto ≥1 trial between 2009 and 2015. Fourteen patients participated in multiple trials, and a total of 113 trial encounters were reviewed in this retrospective study. Eighty-three percent of patients with molecular data available were able to participate in trials matched to molecular aberrations. Patients who were treated on matched studies had improved clinical benefit (RR: 1.80, p = 0.005), progression-free (HR: 0.52, p = 0.003) and overall survival (HR: 0.54, p < 0.001). Treatment was well tolerated with low rates of treatment discontinuation for toxicity (8% overall) that did not differ between groups. No toxicity-related deaths were observed.Conclusions Molecular profiling for MBC patients in a phase I setting is feasible and aids therapeutic decisions with improved patient outcomes

Neutrophil to lymphocyte ratio and response to tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma

477 Background: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are markers of host inflammation and have prognostic value in many solid tumors. Here we aimed to explore the association of NLR and PLR with response to tyrosine kinase inhibitor (TKI) treatment in metastatic renal cell carcinoma (mRCC). Methods: Data from patients with mRCC treated at the Princess Margaret Cancer Centrein Toronto with a TKI as first-line treatment were retrospectively collected. The association of several variables with response to treatment (complete response [CR] or partial response [PR] vs. stable disease &gt; 3 months [SD] or progressive disease [PD]) was assessed by binary logistic regression. Significant variables were dichotomized and cut-offs selected by the area under the receiver operating characteristic (AUC) curve. Results: Data from 157 patients treated between 11/2004 and 09/2012 were analyzed. Median age at start of TKI treatment was 61 years and first-line treatment was sunitinib, sorafenib, and other in 49%, 43%, and 8% of patients, respectively. Best response was CR/PR, SD, and PD in 27%, 55%, and 18% patients. On multivariable analysis NLR &gt; 2.5 and Karnofsky Performance Status (KPS) &lt; 90% were associated with a lower likelihood of response and each allocated a score of 1 unit. Response rates for a score of 0, 1, or 2 were 45% (29-61%), 28% (17-38%), 10% (1-19%), respectively. PLR did not retain association with response in multivariable analysis. Conclusions: NLR and KPS are associated with response to TKI treatment in mRCC. Data from an external validation set will also be presented. </jats:p