Dorff, Tanya B.

4563 Background: We previously reported no difference in favorable response rate (FRR) or PFS for TIP vs BEP. Here we present results of a pre-planned analysis of biomarkers of outcome. Methods: HCG and AFP were drawn on days 1 and 15 of each cycle and rates of decline classified as satisfactory [S] or unsatisfactory [US] by MSK (Motzer JCO 2007) and GETUG (Fizazi Lancet Oncol 2014) methods. IHC for ERCC1, RAD51, PARP1, HER-2, and p-AKT was performed on pre-treatment tumor samples. An H-score (0 – 300) was calculated for each stain (H = stain intensity [0 – 3] x % positive cells [0-100]). H-score and marker decline category were correlated with FRR (PR + CR) and PFS. Patients (pts) who received disease-stabilizing chemotherapy were excluded from marker analyses. Results: Of 91 pts, 80 did not receive disease-stabilizing treatment with 79 having sufficient marker values for analysis by the MSK method and 75 by GETUG. By MSK, 49 had S decline vs 30 US; by GETUG, 34 S vs 41 US. FRR and PFS were improved for pts with S vs US decline by both methods and remained significant by the MSK method when stratified by IGCCCG group (Table). IHC (n=77) quality was adequate in 71 to 73 pts (varied by stain) and was positive (H >0) for PARP in 68/73, ERCC1 in 54/71, RAD51 in 54/73, p-AKT in 5/72, and HER2 in 4/72. Only PARP1 was associated with outcome with worse PFS for the lowest expression tertile (H < 180; p=0.013). Conclusions: PARP1 expression and tumor marker decline rates, particularly by MSK method, were significantly associated with outcome to initial chemotherapy in int/poor risk GCT. Future trials incorporating marker decline into treatment allocation and validating the prognostic effect of PARP1 expression are warranted. Clinical trial information: NCT01873326. [Table: see text]

The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.

5023 Background: Skeletal-related events (SREs) drive morbidity in patients with metastatic castration-resistant prostate cancer (mCRPC). In the ALSYMPCA study, Radium-223 (Ra223) was found to palliate pain in addition to prolonging survival and reducing SREs. Earlier onset of pain relief was noted when zoledronic acid (ZA) was administered within 24-48 hours of samarium; we evaluated whether the timing of bone supportive therapy (BST) affected pain palliation fromRa223. Methods: We identified patients who received Ra223 at University of Southern California or Mayo Clinic Arizona. Data extracted: Ra223 administration dates, pain scores, pain medications, ZA or denosumab administration dates, alkaline phosphatase (ALP) levels, prostate specific antigen (PSA) levels, and concurrent prostate cancer therapy. Patients were evaluable for pain response if they had at least 2 pain scores documented before and after Ra223 with pain medication use data. Pain response was defined as > 2 point decrease in pain on a 10 point scale; flare was defined as > 2 point increase followed by return to baseline or lower. Results: Of 65 patients, 20 had baseline pain score > 0 and 34 were evaluable. Median #doses Ra223 was 5 (range 2-6). 18 patients received concurrent abiraterone (abi) or enzalutamide (enza), 16 did not. Pain response occurred in 6/6 (100%) patients who received BST within 1 month prior to first Ra223 dose and 4/8 (50%) patients who did not receive BST. Pain flare occurred in 6/21 patients (29%) without BST and 2/13 (15%) with BST. 6/10 (60%) patients with pain response had ALP decline but there was no consistent pattern of ALP changes in patients with flare. 8/8 patients with pain response had no PSA decline (6 increased, 2 stable). 6/12 (50%) and 2/22 (9%) patients on abi/enza had pain response and flare respectively, and 4/8 (50%) and 6/19 (32%) patients without concurrent abi/enza had response/flare. Conclusions: BST within 1 month prior to first Ra223 may be associated with increased likelihood of pain palliation and may prevent pain flare. PSA/ALP changes do not predict pain response. Concurrent use of abi/enza does not increase the likelihood of pain response and may decrease the likelihood of flare.