PARP Inhibitor Rucaparib In Patients Research Articles

Abstract 966: Exploration of a novel HRD signature (HRDsig) as a biomarker for rucaparib benefit in ARIEL2

Abstract Introduction: The ARIEL2 (Parts 1 and 2) all-comers study tested the effectiveness of the PARP inhibitor rucaparib in patients (pts) with platinum-sensitive or resistant/refractory relapsed high-grade ovarian cancer. Pre-specified analyses identified associations of BRCA1/2 mutation status and genomic LOH (gLOH) with prolonged PFS. Recently, a novel scar-based measure of HRD was described [HRDsig; AACR #1249], and we retrospectively examined its predictive value in the ARIEL2 study. Methods: ARIEL2 (CO-338-017; NCT01891344) was an international multicenter, two-part, phase 2 open-label study conducted across 64 sites. Tumor tissues were profiled with comprehensive genomic profiling for all classes of alterations in at least 287 genes (FoundationOne®). HRDsig was called using a machine learning based algorithm with a broad set of genome-wide copy number and short variant features, independent of gLOH (AACR 2022 #1249). Survival analysis was limited to samples where both gLOH and HRDsig could be evaluated (n=394). Hazard ratios were estimated using a univariate Cox proportional hazards model and objective response rates (ORR) were compared using Fisher’s exact test. gLOH high was defined using a cutoff of 16%, based on ARIEL2 and subsequently FDA approved as a complementary diagnostic. BRCA1 promoter methylation was quantified by digital droplet PCR. Results: HRDsig(+) was identified in 56% (251/449) of cases, including 92% (108/117) of those with deleterious BRCA1/2 alterations and 43% (143/332) of BRCAwt. In the intention to treat (ITT) and in pts with platinum sensitive (plat-sen) disease, HRDsig(+) was predictive of PFS benefit on rucaparib (ITT HR = 0.63 [0.50-0.80], p<0.001; plat-sen HR = 0.44 [0.32-0.60]; p<0.001), similar to gLOH-high (ITT HR = 0.70 [0.56-0.87], p=0.0016; plat-sen HR 0.55 [0.41-0.74], p<0.001). In BRCAwt pts with plat-sen disease (n=179), HRDsig was predictive of objective response and PFS on rucaparib, (ORR 28% in HRDsig(+) vs 10% in HRDsig(-), p=0.002; PFS HR = 0.66 [0.48-0.91]; p=0.012). Tumors with RAD51C/D alterations (5/5; 100%) were identified as HRDsig(+). Most other HRR alterations showed little association with HRDsig, including ATM (0/5 HRDsig(+)), and CHEK2 (0/4 HRDsig(+)). Additionally, 33 BRCAwt pts were identified as BRCA1 methylation positive in the cohort, with 32/33 (97%) identified as HRDsig(+), similar to gLOH-high (30/33; 91%). Conclusions: HRDsig(+) was associated with rucaparib benefit overall and in BRCAwt pts with platinum-sensitive ovarian cancer in this study. HRDsig(+) status exhibited strong association with deficiency caused by both epigenetic (BRCA1 methylation) and genetic (HRR mutation) mechanisms. Additional studies should further explore the utility of this biomarker for pt selection in ovarian cancer and other relevant cancer types to inform the use of PARP inhibitors or other DNA damaging agents. Citation Format: Ethan S. Sokol, Russell W. Madison, Dexter X. Jin, Kuei Ting Chen, Zoe Fleischmann, Justin Newberg, Alexa Shrock, David Fabrizio, Jie He, Neeru Bhardwaj, Kevin K. Lin, Iain A. McNeish, Elizabeth M. Swisher. Exploration of a novel HRD signature (HRDsig) as a biomarker for rucaparib benefit in ARIEL2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 966.

Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

BackgroundATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).MethodsPatients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks.ResultsOf 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration.ConclusionsRucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.Trial registrationThis trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017–004166-10).

Genomic characteristics of deleterious BRCA1 and BRCA2 alterations and associations with baseline clinical factors in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TRITON2.

5031 Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in patients with mCRPC who have a deleterious germline or somatic alteration in BRCA ( BRCA1 or BRCA2) or 1 of 13 other DNA damage repair genes. Here we present analyses of tumor genomics and baseline clinical characteristics in mCRPC patients with a deleterious alteration in BRCA. Methods: Plasma (baseline) and tissue (archival or baseline) samples from patients with a deleterious alteration in BRCA were analyzed using Foundation Medicine next-generation sequencing assays. The alterations and zygosity of the alterations that were detected, as well as the somatic/germline status from Color Genomics testing, were summarized. Associations between genomic alterations, DNA yield, allele frequency, and baseline clinical characteristics were investigated. Results: Results are shown in the Table for a cohort of 40 BRCA2 and 5 BRCA1 patients enrolled in TRITON2 (Abida W et al. Presented at ESMO 2018. Abst 793PD). A biallelic alteration was observed in 21 of the 22 BRCA2 patients (95%) for whom alteration zygosity could be determined. Among the 5 BRCA1 patients, 1 alteration was monoallelic and 4 were of unknown zygosity. Co-occurring alterations in cancer-related or DNA damage repair genes were observed in many patients with BRCA alterations. At baseline, cell-free DNA (cfDNA) yield correlated positively with the sum of target lesions (STL; P= 0.04), but not with prostate-specific antigen (PSA) levels ( P= 0.86). No correlation was observed between allele frequency of the BRCA alteration baseline STL ( P= 0.68) or PSA levels ( P= 0.97). Conclusions: Patients with a BRCA mutation enrolled in TRITON2 demonstrate a profile of genomic alterations consistent with that of prior studies of patients with mCRPC. Plasma cfDNA profiling showed a correlation between baseline cfDNA yield and measurable tumor burden, but not baseline PSA. Clinical trial information: NCT02952534. [Table: see text]

TRITON2: An international, multicenter, open-label, phase II study of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD).

TPS388 Background: Up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM or another homologous recombination (HR) DNA repair gene that can serve as a molecular marker to select those who may respond to poly(ADP-ribose) polymerase inhibitors (PARPis). PARPis are lethal to cells with HRD, and PARPi treatment has shown preliminary evidence of an antitumor effect in patients with mCRPC who harbor a mutation in an HR DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent PARP1, PARP2 and PARP3 inhibitor, in patients with mCRPC associated with HRD. Methods: TRITON2 (NCT02952534) is a phase 2 study evaluating rucaparib 600 mg BID in patients with mCRPC. Patients with a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per prior local test or central test during screening) will be enrolled into 1 of 2 cohorts based on the presence or absence of measurable visceral and/or nodal disease. An exploratory cohort will enroll patients with an alteration in any of 12 other prespecified HR genes (eg, RAD51C, RAD51D and PALB2), with or without measurable visceral and/or nodal disease. Patients must have progressed on androgen receptor signaling–directed therapy and 1 prior taxane-based chemotherapy for mCRPC. Patients who received prior treatment with a PARPi, mitoxantrone, cyclophosphamide or platinum-based chemotherapy are excluded. The primary endpoint is objective response rate measured using modified RECIST v1.1/PCWG3 for patients with soft-tissue disease and prostate-specific antigen response for patients with nonmeasurable disease. Secondary endpoints include duration of response, radiographic progression-free survival, overall survival, clinical benefit rate and safety. Pretreatment blood samples collected from all patients will enable development of a plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈160) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02952534.

Abstract LB-A12: Results from the phase 3 study ARIEL3: mutations in non-BRCA homologous recombination repair genes confer sensitivity to maintenance treatment with the PARP inhibitor rucaparib in patients with recurrent platinum-sensitive high-grade ovarian carcinoma

Abstract Background: High-grade ovarian carcinomas (HGOC) with a mutation in BRCA1/2 or other core homologous recombination repair (HRR) genes are sensitive to treatment with the PARP inhibitor rucaparib. To study whether HRR gene mutations confer sensitivity to rucaparib in the maintenance setting, we performed next-generation sequencing (NGS) on carcinomas from a double-blind, placebo-controlled, phase 3 study of rucaparib in patients with HGOC following response to platinum-based chemotherapy (ARIEL3, NCT01968213). Materials and Methods: Archival ovarian carcinoma specimens were required for all 564 patients who were randomized in ARIEL3 and were sequenced using Foundation Medicine’s NGS-based assay to identify deleterious mutations in a prespecified list of HRR genes (BRCA1/2 and 28 non-BRCA HRR genes, including ATM, BARD1, BRIP1, CHEK2, RAD51C, RAD51D, RAD54L, and FANC family genes). Patients were randomized 2:1 to receive oral rucaparib 600 mg twice daily or placebo. The randomization was stratified by HRR gene mutation status (BRCA, non-BRCA HRR, no mutation in BRCA or HRR gene), progression-free interval of the penultimate platinum-based regimen, and best response to most recent platinum regimen. The primary endpoint for ARIEL3 was investigator-assessed progression-free survival (PFS) per RECIST v1.1. Exploratory analysis of confirmed response was conducted for the subgroup of patients with measurable disease at study entry. Results: Deleterious mutations in non-BRCA HRR genes were detected in ovarian carcinoma specimens from 7.6% (43/564) of randomized patients. In these patients, PFS was significantly longer with rucaparib than with placebo (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.50; P=0.0005), with a median PFS of 11.1 mo and 5.5 mo, respectively. This HR is similar to that found in women with carcinomas containing a BRCA1/2 mutation (0.23; 95% CI, 0.16-0.34). The most commonly found non-BRCA HRR gene mutations among the 28 patients in the rucaparib arm were RAD51C (n=6) and RAD51D (n=4) and among the 15 patients in the placebo arm were BRIP1 (n=5) and RAD51C (n=2). A diverse set of mutation types were detected, including frameshift insertions/deletions, homozygous deletions, and nonsense and splice site mutations. All 10 RAD51C/D mutations were homozygous within the carcinomas, indicating biallelic loss. Additionally, all RAD51C/D-mutant carcinomas exhibited high genomic loss of heterozygosity, which is a type of genomic scar characteristic of HRR deficiency. At the visit cutoff date (15 April 2017), only 2 of the 10 RAD51C/D cases in the rucaparib arm had disease progression; 7 had a PFS duration of at least 1 y (median PFS, 16.4 mo; range 5.4+ to 30.4+ mo). Three of the RAD51C/D cases were in the subgroup of patients who had measurable disease at baseline, and all achieved a confirmed response (1 complete response and 2 partial responses). In comparison, the 3 RAD51C/D cases in the placebo arm had a median PFS of 5.4 mo (range, 3.9 to 5.5 mo). Conclusions: Patients with recurrent platinum-sensitive HGOC harboring a deleterious mutation in non-BRCA HRR genes (including RAD51C/D) had significantly longer PFS with rucaparib maintenance treatment than with placebo. Citation Format: David M. O'Malley, Robert L. Coleman, Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Iain A. McNeish, Elizabeth M. Swisher, Clare L. Scott, Gottfried E. Konecny, Heidi Giordano, Terri Cameron, Lara Maloney, Sandra Goble, James Sun, Thomas C. Harding, Kevin K. Lin, Jonathan A. Ledermann. Results from the phase 3 study ARIEL3: mutations in non-BRCA homologous recombination repair genes confer sensitivity to maintenance treatment with the PARP inhibitor rucaparib in patients with recurrent platinum-sensitive high-grade ovarian carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr LB-A12.

P048 - The TRITON clinical trial programme: evaluation of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

P048 - The TRITON clinical trial programme: evaluation of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

The TRITON clinical trial programme: evaluation of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

The TRITON clinical trial programme: evaluation of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

836TiP - The TRITON clinical trial programme: Evaluation of the PARP inhibitor rucaparib in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

836TiP - The TRITON clinical trial programme: Evaluation of the PARP inhibitor rucaparib in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD)

BRCA1 and RAD51C promoter hypermethylation confer sensitivity to the PARP inhibitor rucaparib in patients with relapsed, platinum-sensitive ovarian carcinoma in ARIEL2 Part 1

BRCA1 and RAD51C promoter hypermethylation confer sensitivity to the PARP inhibitor rucaparib in patients with relapsed, platinum-sensitive ovarian carcinoma in ARIEL2 Part 1

Abstract AP28: BRCA1 and RAD51C Promoter Hypermethylation Confer Sensitivity to PARP Inhibitors in Patients with Platinum Sensitive Ovarian Carcinoma

Abstract Germline and somatic mutations in BRCA1 and BRCA2 (BRCA) confer PARP inhibitor sensitivity. Promoter hypermethylation is an alternate mechanism of gene down-regulation, and BRCA1 promoter methylation is relatively common in sporadic ovarian cancer. The clinical significance of BRCA1 methylation is less clear than for mutations, as the Cancer Genome Atlas (TCGA) and others have failed to show improved survival in ovarian carcinomas with BRCA1 methylation. No one has previously tested whether BRCA1 methylation confers in vivo sensitivity to PARP inhibitors in patients with ovarian cancer. ARIEL2 is a phase 2 study of the PARP inhibitor rucaparib in patients with recurrent platinum sensitive high-grade ovarian, peritoneal or fallopian tube carcinoma. At enrollment, ARIEL2 required pre-treatment tumor biopsies with the goal of developing tissue predictors of PARP inhibitor sensitivity other than BRCA mutations. The number of women with known germline mutations was capped at 15 patients in order to predominantly enroll BRCA wildtype cases. As presented at ASCO 2016, in cases with no BRCA mutations, a high fraction of genomic loss of heterozygosity (LOH) significantly predicted a better progression-free survival (the primary endpoint), longer duration of response, and a higher fraction of responders compared to cases with low LOH. We assessed BRCA1 and RAD51C promoter hypermethylation using methylation-sensitive polymerase chain reaction in paired archival and pre-treatment biopsies from patients on ARIEL2. Of 165 cases for which methylation analyses were completed, 21 (12.7%) were methylated at the BRCA1 promoter and four (2.4%) at the RAD51C promoter. Methylation of BRCA1 and RAD51C was mutually exclusive with mutation in BRCA or other homologous recombination genes. All four cases with RAD51C methylation and 15/19 (78.9%) with BRCA1 methylation were associated with high LOH. In 90 paired samples archival and pre-treatment tissues, RAD51C methylation was 100% concordant and BRCA1 methylation was highly concordant (p<0·001). For 13 cases with BRCA1 methylation in the archival specimen, 4 (30·8%) were unmethylated in the paired pretreatment tumor, but for 77 unmethylated archival specimens, gain of methylation in the pretreatment biopsy was observed just once. Confirmed RECIST responses were seen in 52.4% (11/21) BRCA1 methylated and 75.0% (3/4) RAD51C methylated cases. In conclusion, BRCA1 and RAD51C methylation in ovarian carcinomas correlates with a high response rate to PARP inhibitors. If methylation was to be used as a predictor of PARP inhibitor sensitivity, it would need to be assessed in a pre-treatment (not archival) specimen. The loss of BRCA1 methylation in recurrent ovarian carcinoma, which was common even in these platinum sensitive cases, could explain why BRCA1 methylation is associated with similar survival to methylated cases, despite initial improved therapeutic sensitivity. Citation Format: Elizabeth Swisher, Maria Harrell, Kevin K. Lin, Clare Scott, Sandra Goble, Amit Oza, Robert L. Coleman, Gottfried Konecny, Anna V. Tinker, David M. O'Malley, Rebecca Kristeleit, Ling Ma, James Brenton, Katherine Bell-McGuinn, Ana Oaknin, Alexandra Leary, Elaina Mann, Heidi Giordano, Mitch Rapon, Iain McNeish, Scott H. Kaufmann. BRCA1 and RAD51C Promoter Hypermethylation Confer Sensitivity to PARP Inhibitors in Patients with Platinum Sensitive Ovarian Carcinoma [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP28.

20 - Secondary mutations in RAD51C and RAD51D are associated with acquired resistance to the PARP inhibitor rucaparib in patients with high-grade ovarian cancer

20 - Secondary mutations in RAD51C and RAD51D are associated with acquired resistance to the PARP inhibitor rucaparib in patients with high-grade ovarian cancer

219TiP - Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)

219TiP - Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)

RUCAPANC: An open-label, phase 2 trial of the PARP inhibitor rucaparib in patients (pts) with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation.

4110Background: Pts with PC have a poor prognosis and limited treatment options. Around 9% of pts with PC have a germline or somatic BRCA mutation. Recent studies showed that rucaparib effectively ...

Abstract B102: A phase 2, open-label study of the PARP inhibitor rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation

Abstract Background: Despite the recent progress made with front-line treatment for advanced pancreatic cancer (PC), most patients (pts) will either relapse or be refractory to treatment. Others may not even be eligible due to the toxicity profile of the available options or due to clinical deterioration. Once the disease progresses following front-line treatment, there is no accepted standard of care. Treatment options are clearly needed for patients with refractory disease. Approximately 5% of unselected PC pts, 10% of PC patients of Ashkenazi Jewish descent, and up to 19% of familial PC cases, harbor a germline BRCA mutation. Though less well characterized to date, somatic BRCA mutations also appear to play a significant role in PC. Clinical data have shown that pts with BRCA-mutant (BRCAmut) tumors, including those with PC, respond to treatment with a PARP inhibitor (PARPi). Early data suggest that other genomic characteristics may be surrogate biomarkers of homologous recombination deficiency (HRD) and define a larger group of responders than just BRCA mutation(s) alone. Rucaparib, an oral PARPi, is being developed for treatment of cancers associated with HRD due to a BRCA mutation or other homologous recombination pathway defect. Rucaparib has a desirable PK profile, is well tolerated, and has demonstrated clinical activity (RECIST and/or CA-125 responses) in patients with BRCAmut pancreatic, ovarian, or breast cancer in an ongoing Phase 1/2 study (NCT01482715). Three studies are currently ongoing in ovarian cancer and a trial in BRCAmut pancreatic cancer is now planned. The clinical activity of PARPi, including rucaparib, in BRCAmut PC, combined with the paucity of active 2nd-line therapies, support evaluation of rucaparib in PC pts with a BRCA mutation. Methods: Study CO-338-023 (NCT02042378) is a single-arm, open-label Phase 2 trial of continuous monotherapy rucaparib in up to 100 pts with pancreatic ductal adenocarcinoma (or related subtype) who are known to harbor a deleterious BRCA mutation (germline or somatic). Pts must have received at least 1, but no more than 2, prior regimens for locally advanced or metastatic disease and have relapsed / progressive disease confirmed by radiologic assessment, or are no longer able to tolerate chemotherapy due to toxicity, and radiologic assessment confirms stable or progressive disease. Other key inclusion criteria include measurable disease, ECOG Performance Status 0 or 1, and adequate organ function. Pts with endocrine tumors or who received prior PARPi treatment are excluded. Pts will take 600 mg BID rucaparib continuously and be evaluated for safety every 2–4 wks, disease status (CT scans, CA19–9) every 4–8 wks until disease progression, and then for survival every 4 wks. Blood and archival tumor tissue (if available) will be collected from all pts. The primary endpoint is ORR by RECIST v1.1. Key secondary endpoints include duration of response, PFS, OS, and safety. Exploratory analyses include gene sequence and structural rearrangements of tumor DNA and evaluation of circulating tumor DNA. A group sequential interim monitoring plan will be implemented to stop the study early for either superior efficacy or futility. Interim analyses will occur after every 10th patient enrolled has sufficient disease assessment data available. If robust activity is observed in the BRCAmut PC population, the trial may be broadened to include PC pts with HRD due to other than a BRCA mutation. The trial will be open to enrollment at clinical sites in the US and Israel in 2Q 2014. Citation Format: Susan M. Domchek, Robert McWilliams, Andrew Hendifar, Rachna T. Shroff, Lawrence Leichman, Ron Epelbaum, Ravit Geva, George Kim, Steven R. Alberts, Robert A. Wolff, Andrew Allen, Heidi Giordano, Mitch Raponi, Jeff Isaacson, Lindsey Rolfe, Andrew Biankin, Robert H. Vonderheide. A phase 2, open-label study of the PARP inhibitor rucaparib in patients with pancreatic cancer and a known deleterious BRCA mutation. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B102.