Citations

9090 Background: We identified factors associated with better OS for previously treated, PD-L1–expressing advanced NSCLC using data from KEYNOTE-010 (NCT01905657; Herbst et al. Lancet. 2016;387:1540-50), in which pembrolizumab had superior OS over docetaxel. Methods: 1033 patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel 75 mg/m2 Q3W. Response was assessed per RECIST v1.1 by independent central review. Multivariate analyses were performed using a Cox proportional hazards regression model on OS in the pembrolizumab arms. A set of variable selection methods was applied to 19 baseline demographic and disease characteristics, including smoking status, and identified 7 factors that contributed to OS. Data cut was September 30, 2016. Results: Adjusted hazard ratios (HRs) for the factors in the pembrolizumab arm from the model are shown in the Table. Updated OS with an additional 6 months of follow-up from this data lock for KEYNOTE-010 will be presented. Conclusions: While the overall result of KEYNOTE-010 revealed improved OS with pembrolizumab compared with docetaxel in previously treated patients with PD-L1–positive advanced NSCLC, exploratory, post hoc multivariate analyses showed that some laboratory and tumor characteristics such as nonsquamous histology, normal baseline lactate dehydrogenase (LDH), PD-L1 TPS ≥50%, and wild-type EGFR mutation status were associated with better OS among patients treated with pembrolizumab. Clinical trial information: NCT01905657. [Table: see text]

e18154 Background: Due to an increase in the elective decision to pursue contralateral prophylactic mastectomy (CPM), the incidence of bilateral mastectomy (BM) with/without postmastectomy reconstruction (R) [BM+/-R] has increased in the last decade. While prior studies at academic centers have investigated concerns regarding its impact on subsequent cancer therapy, we hypothesized that BM+/-R is associated with a delay in initiation of adjuvant therapy (AT) in a community oncology clinic. Methods: This study involved chart review of all patients who underwent mastectomy as definitive surgery for stage I-III breast cancer between 2007 and 2012 and were subsequently followed at Essentia Health Cancer Center. The primary endpoint of the study was the proportion of patients receiving subsequent AT within 6 weeks of surgery (TST6) when compared between different surgical groups. Results: A total of 478 patients were included in the study, with a median age of 63 years. Patients were divided into 4 groups, BM-R (n = 133), BM+R (n = 73), unilateral mastectomy (UM) –R (n = 244) and UM+R (n = 28). Significant demographic differences were identified between the groups including age ( p< 0.001), medical comorbidities ( p< 0.001), and BMI ( p< 0.001). The incidence of any major post-operative complication (including flap/implant failure, infection and wound necrosis/dehiscence) or additional surgeries within 6 weeks of surgery was higher in patients undergoing reconstruction, [BM+R (19%) and UM+R (18%)] compared to those who did not [BM-R (6%) and UM-R (4%)] ( p< 0.001). Patients having major complications or needing additional surgeries within 6 weeks had a lower adjusted likelihood of achieving TST6 compared to those who did not (OR = 0.35; p= 0.009). However, there was no significant difference in TST6 between the surgical groups ( p= 0.31). Conclusions: Immediate post-mastectomy reconstruction is associated with a significantly increased risk of postoperative complications or need for additional surgeries within 6 weeks. In an appropriately selected patient population, CPM and reconstruction do not significantly delay subsequent AT in a community oncology clinic.

5000 Background: It is clinically challenging to integrate genomic classifier results that report a continuous numerical risk of recurrence into treatment decisions for prostate cancer (PCa). We aimed to develop a novel clinical-genomic risk system that can readily be incorporated into treatment guidelines for localized PCa. Methods: Four multi-center cohorts (n = 6928 men; 5937 prospective samples and 991 retrospective samples with long-term follow-up) were utilized to identify and validate our clinical-genomic risk system in radical prostatectomy (RP) samples and subsequently in pre-treatment biopsy samples. All patients’ FFPE tissue underwent microarray analysis, and the expression values for 22 prespecified biomarkers that constitute Decipher were extracted. Cumulative incidence curves were constructed to estimate metastasis risk. C-indices were calculated to compare NCCN and CAPRA score to our clinical-genomic system. Results: With a median follow-up of 8 years for men in our RP cohort, the 10-year distant metastasis rates for NCCN low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.8%, 9.4%, 40.1%, and 41.4%, respectively. Our 3-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.7%, 30.7%, and 57.7%, for low, intermediate, and high-risk, which were validated in our pre-treatment biopsy cohort with 10-year rate of distant metastasis of 0%, 30.3%, and 63.2%, respectively. C-indices for the clinical-genomic system (0.84, 95%CI 0.62-0.92) were significantly improved over NCCN (0.71, 95%CI 0.59-0.84) and CAPRA (0.71, 95%CI 0.60-0.81) score. A total of 33.4% of men would be reclassified by the clinical-genomic system, and specifically 17.1%, 41.3%, and 19.4% of men in NCCN low, intermediate and high risk groups would be reclassified by our new system. Conclusions: The use of a readily available genomic classifier in combination with clinicopathologic variables can generate a simple to use 3-tier clinical-genomic risk system that is highly prognostic for distant metastasis, is more accurate than clinical risk, and can be easily incorporated into NCCN guidelines to inform treatment decisions.