Overall Survival Benefit In Patients Research Articles

World Health Organization Grade II Meningiomas: The Role of Adjuvant/Salvage Gamma Knife Surgery After Initial Surgery and Prognostic Factor Assessment.

This study was performed to evaluate the efficiency of Gamma Knife surgery (GKS) on reducing recurrence of World Health Organization (WHO) grade II meningiomas after surgery and to define the risk factors associated with tumor recurrence/progression and patient's death. This retrospective study included 75 patients who were diagnosed with WHO grade II meningiomas after initial surgery. The Kaplan-Meier method with a log-rank test was used to calculate the survival curves. Univariate and multivariate Cox proportional hazards model were used to identify the risk factors associated with tumor recurrence/progression and patient's death. The median follow-up period was 70 months. The overall survival (OS) was 97.2% at 2 years and 89.8% at 5 years. The progression-free survival (PFS) at 1, 3, and 5 years was 89.3%, 72.6%, and 59.3%, respectively. Comparing the effects on PFS and OS between different groups, there were no statistically significant differences between the surgery-alone group and the surgery with adjuvant/salvage GKS group (P= 0.512; P= 0.949). In multivariate Cox proportional hazards model analysis, extent of resection (P= 0.001) and tumor location (P= 0.015) were associated with tumor recurrence; only histologic subtypes (P= 0.005) were associated with patient's death. There was no significant PFS or OS benefit for patients with WHO grade II meningiomas treated with adjuvant/salvage GKS postoperatively. Convexity meningiomas with gross total resection tended to benefit PFS. We suggest trying to achieve maximum safe gross total resection for patients with WHO grade II meningiomas, then following up closely.

Clinical Potential of Statins in Prostate Cancer Radiation Therapy.

Statins are cholesterol- lowering drugs that have been shown to possess anti-tumour properties. Observational studies have shown that 3-hydroxy-3-methlyglutaryl coenzyme A reductase inhibitor (statin) use may be associated with reduced prostate cancer risk. Preclinical studies suggest that statins possess anticancer and radiosensitising properties. This review aims to determine the impact of statin use in the efficacy of radiation therapy and the therapeutic window in prostate cancer. The scientific databases PubMed, Science Direct, EMBASE, Cochrane Collaboration, and Google Scholar were searched for articles identifying statin use in histologically confirmed prostate cancer treated with external beam radiation therapy. Improvement was observed in freedom from biochemical failure (91% vs. 79%), relapse free survival (72% vs. 69%), distant metastasis free survival (96% vs. 94%), and prostate-specific antigen (PSA) relapse free survival (89% vs. 83%) with statin use, however this did not translate into an overall survival benefit for patients. Conflicting data concerning clinical outcomes reduce the integrity of these findings. The literature supports the radiosensitising properties of statins and their potential antitumor effects in prostate cancer. Statin use in prostate cancer presents many obstacles yet to be overcome, which warrant attention prior to the routine implementation of statins in treatment regimes. However, there is evidence to support their beneficial use.

Real-World Utilization Of Blinatumomab In Acute Lymphoblastic Leukemia In The US

Blinatumomab is the first bispecific CD19 directed CD3 T-cell engager immunotherapy to demonstrate overall survival benefit in patients with Philadelphia chromosome-negative (Ph-) relapsed/refractory acute lymphoblastic leukemia (ALL). In December 2014 the FDA granted an accelerated approval to blinatumomab in patients with Ph- relapsed/refractory B-precursor ALL based on findings from a phase II trial in 185 adults followed by the supplemental BLA approval to include new data in pediatric patients. Approved on 12/3/2014, blinatumomab is the first CD19 targeting bi-specific T-cell engagers (Bites) in the immuno-oncology arsenal. As it will likely compete with CD19 targeted CAR-T therapeutics, its uptake since approval may predict CAR-T potential in a similar clinical setting. Patients diagnosed with ALL on systemic therapy (ST) between 12/2014 and 12/2016 were identified from the Symphony Health claims database. Market share and time to treatment discontinuation (TTD) were examined. TTD was defined as time from ST initiation to switch or last administration date plus 90 days if no other ST was administered. TTD was described with Kaplan-Meier curves. Of the 18,162 ALL patients on ST since blinatumomab approval, 218 (1.2%) were treated with blinatumomab; of them 29 (13.3%) appeared to be Ph+ (indicated by utilization of nilotinib, ponatinib, dasatinib, imatinib, or bosutinib). The most common regimen was blinatumomab monotherapy followed by combination with methotrexate and/or cytarabine. Of the 218 patients treated with blinatumomab, 123 (56.4%) were male, 83 (38.1%) received blinatumomab in the first-line, and mean (SD) age was 43.9 (18.0) years. The mean (SD) number of prior antineoplastic regimens was 3.2 (3.6). Mean (median) TTD was 122.5 (110.0) days. This is the first real-world evidence study of blinatumomab and it demonstrates the uniqueness of the patient population for which it is currently indicated. CAR T-cell economic modeling should be informed by this research.

Salvage Re-Irradiation for Recurrent High-Grade Glioma and Comparison to Bevacizumab Alone

High-grade gliomas (HGGs) are the most common lethal primary brain tumor in adults and almost always recur after initial treatment. Despite this, there is little evidence arguing superiority of a single treatment strategy at time of recurrence, with options including supportive care, re-resection, systemic therapy, or re-irradiation. While bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is now commonly used for recurrent HGG, there has been longstanding interest in re-irradiation for patients with local-only recurrence. The purpose of this study is to examine outcomes of patients with recurrent HGG treated with re-irradiation. This is a retrospective analysis of patients with recurrent HGG who received salvage re-irradiation at a major academic institution from 2010-2014, as well as those who received bevacizumab alone. Progression-free survival (PFS) and overall survival (OS) were calculated from date of re-irradiation completion, or date of bevacizumab initiation in the bevaciumab alone cohort. Cox proportional hazards modeling was used to examine factors associated with OS. Propensity score modeling was used to compare survival after re-irradiation vs. bevacizumab alone. Sixty-seven patients received re-irradiation for recurrence, and 177 patients received bevacizumab alone. Among the re-irradiation cohort, 51% received concurrent bevacizumab. Median time in the re-irradiation cohort from initial diagnosis to re-irradiation was 31.4 months. The most common re-irradiation dose/fractionation regimens were 6 Gy x 5 (36%), 3.5 Gy x 10 (21%), 2.67 Gy x 15 (15%), and 18-20 Gy x 1 (15%). No early or late toxicities > grade 2 were observed. Median PFS and OS after re-irradiation were 4.8 months 10.7 months, respectively. Number of progressions prior to re-irradiation (adjusted hazard ratio [AHR], 1.6; 95% CI, 1.1-2.3; P = .007), and recurrence in a new brain location (vs. local-only; AHR, 7.4; 95% CI, 2.4-23.1; P < .001) were associated with OS; dose/fractionation regimen was not. Compared to bevacizumab alone, patients who received re-irradiation had a non-significant increase in OS (HR, 0.80; 95% CI, 0.53-1.23; P = .31). Among patients with local-only recurrence, there was a trend towards longer median OS after re-irradiation compared to bevacizumab alone (12.4 vs. 8.0 months; P = .12). Re-irradiation for recurrent HGG appears safe and was associated with reasonable PFS and OS even as many patients received bevacizumab and had >2 prior progressions. Number of progressions prior to re-irradiation and recurrence location were associated with OS, while dose/fractionation regimen was not. While re-irradiation was not associated with OS benefit in propensity score adjusted analysis compared with bevacizumab alone, there was a trend towards OS benefit in patients with local-only recurrence.

The Contemporary Use of Radium-223 in Metastatic Castration-resistant Prostate Cancer.

Radium-223 dichloride (radium-223) was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases in the United States and Europe in 2013. This followed a reported overall survival benefit for patients treated with radium-223 and best standard of care (BSoC) when compared with placebo and BSoC in the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial. At that time, docetaxel was the standard first-line choice for patients with metastatic CRPC (mCRPC). Since then, the treatment landscape has changed dramatically with new hormonal agents (abiraterone and enzalutamide) considered to be the first-line choice for many patients. The optimal patient profile for radium-223 in the modern setting, and its best use either in sequence or in combination with other approved agents are unclear, with few definitive guidelines available. This article reports on the views of a group of urologists and medical oncologists experienced in treating patients with mCRPC with radium-223 in routine clinical practice. The aim is to provide an overview of the current use of radium-223 in the treatment of patients with mCRPC, and to discuss best practices for patient selection and on-treatment monitoring. Where agreement was reached, guidance on the optimal use of radium-223 is provided.

Factors Influencing Disease Progression in Patients with Head and Neck Melanoma.

Histological parameters as well as the status of sentinel lymph node are known to be strong prognostic factors in patients with melanoma. In this study, we retrospectively analyzed 1,384 patients who were diagnosed with head and neck melanoma between 1976 and 2010 regarding prognostic factors [tumor thickness, level of invasion, sentinel lymph node (SLN) status, ulceration, histological subtype, localization, and gender], overall survival, and disease-free survival. Patients who developed metastases had a significantly thicker tumor than patients without metastases. Additionally, a thicker tumor was often associated with a higher level of invasion (Clark level). There was no overall survival benefit in patients who underwent SLN dissection when compared to patients who did not (p=0.07). Compared to SLN-negative patients, patients with SLN involvement had a significantly shorter disease-free period (p<0.001) and shorter overall survival time (p<0.001). In summary, tumor thickness is the most important prognostic factor. SLN dissection does not affect the overall survival of patients with melanoma. However, a positive SLN is a marker for a worse outcome in these patients.

Abstract 5648: Combined immune checkpoint targeting with anti-PD-1 plus anti-CD40 antibodies as the most effective approach to eradicate head and neck squamous cell carcinomas (HNSCCs) in mouse models

Abstract Introduction: Immunotherapy with single agent anti-PD-1 antibody confers modest overall survival benefits in patients with recurrent/metastatic HNSCCs. Combined immune checkpoint targeting has shown promising results for melanomas and other solid tumors. Thus, evaluation of combination immunotherapy in animal models specific to HNSCCs could inform prioritization and design of human clinical trials for this disease. We conducted this pre-clinical study to test the hypothesis that combining anti-PD-1 with either anti-CTLA-4 or co-stimulatory immune checkpoint agonist antibodies would be more effective than anti-PD-1 monotherapy in a mouse model of oral carcinoma. We also aimed at identifying the combination regimen with highest anti-tumor activity. Methods: C57BL/6 mice were subcutaneously grafted with 2x106 mouse oral cancer 1 (MOC1) cells derived from a carcinogen-induced tumor molecularly similar to human HNSCC. After 25 days, mice were randomized into one of 12 treatment groups (IgG, or antibodies targeting PD-1, CTLA-4, CD40, OX-40, GITR, 4-1BB, PD-1+CTLA-4, PD1+CD40, PD-1+OX-40, PD-1+GITR, or PD-1+4-1BB), N=8-9 mice/group. Antibodies were administered every 4 days for 3 doses. Tumors were measured twice per week. The primary endpoint was overall survival. Mice were sacrificed when tumor diameter was &amp;gt;2 cm or tumor ulceration was &amp;gt;5 mm. Survival curves were computed using the Kaplan-Meier method and compared using the log-rank (Mantel-Cox) test. Results: In analogy to human clinical trials, anti-PD-1 therapy led to a modest improvement in survival compared to IgG [HR=0.41; 95%CI 0.06-0.53; P=0.015], indicating that this model recapitulates, in part, the effects of immunotherapy in HNSCC patients; none of the animals survived long term. Monotherapy with anti-CTLA-4, anti-CD40, anti-OX-40, or anti-4-1BB also improved survival compared to IgG (P=0.0001, 0.003, 0.02, and 0.003, respectively), but were not more effective than anti-PD-1 alone (P=0.09, 0.12, 0.72, and 0.77, respectively). Combination therapy did not prolong survival compared to anti-PD-1 alone, with the exception of anti-PD-1+ anti-CTLA4 [HR=0.36; 95% CI 0.07-0.6; P=0.016], and anti-PD-1+ anti-CD40 [HR=0.125, 95% CI 0.02-0.24; P=0.0003]. Notably, 50% of mice receiving anti-PD-1+ anti-CD40 antibodies had complete tumor eradication and are alive and disease-free 120 days after tumor grafting. Conclusions: Single agent immunotherapy targeting PD-1, CTLA-4, CD40, OX-40 and 4-1BB modestly improved survival in a mouse model of oral cancer. Combination with anti-PD-1+ anti-CTLA4 and anti-PD-1+ anti-CD40 antibodies outperformed anti-PD-1 monotherapy. Complete responses were exclusively seen with PD-1+CD40 dual targeting. This regimen should be prioritized for evaluation in HNSCC clinical trials. Citation Format: Jose Augusto Monteiro de Oliveira Novaes, Alissa R. Poteete, Marlese A. Pisegna, Uma Giri, Fahao Zhang, Patrick Hwu, John V. Heymach, William N. William. Combined immune checkpoint targeting with anti-PD-1 plus anti-CD40 antibodies as the most effective approach to eradicate head and neck squamous cell carcinomas (HNSCCs) in mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5648. doi:10.1158/1538-7445.AM2017-5648

Impact of adjuvant chemotherapy in non-metastatic node positive bronchial neuroendocrine tumors (BNET).

8533 Background: BNET are a rare and frequently indolent group of neoplasms. Lobectomy is frequently done for patients with non-metastatic disease, and the role of adjuvant chemotherapy for patients with node positive disease (N+) is debated. Methods: Utilizing the National Cancer Database from 2004-2012 we identified 1682 patients with N+ non-metastatic BNET. All patients underwent primary resection, had pathologically confirmed diagnosis, complete follow up data, and were alive &gt; 30 days following surgery. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used to compare 2 groups of patients that differed based on receiving or not adjuvant chemotherapy. Subgroup analyses were performed based on histologic subtypes. Cox proportional hazards was performed to control for age, sex, race, grade, surgical margins, type of surgery, year of diagnosis, Charlson/Deyo Score, insurance, facility type, and location. Results: 651 patients with typical carcinoid (CT), 239 atypical carcinoid (ACT), 426 large cell neuroendocrine carcinoma (LCNEC), and 366 neuroendocrine carcinoma (NEC) were analyzed. The cohort median age was 61, and the female:male ratio was 1.8 for CT, ACT and NEC, and 1 for LCNEC 90% of patients were White and there were no significant differences amongst histologic subtypes. 6% of patients with CT received ADJ-CT, compared to 40% ACT, 42% NEC, and 70% LCNEC. In a multivariate analysis, only increasing age was associated with worse prognosis across all histologic subtypes, and non-academic facility for CT, and male sex for NEC. ADJ-CT was not associated with OS benefit for patients with ACT (HR 1.1; 95% CI 0.68-1.78; p:0.6), was associated with inferior OS in CT (HR: 3.8 (95% CI 1.9-7.0; p = 0.004) and NEC (HR: 2.15; 95% CI 1.5-3.0; p &lt; 0.001), and may provide benefit for LCNEC (HR: 0.67; 95% CI 0.5-0.9; p = 0.009). Conclusions: Adjuvant chemotherapy was not associated with survival benefit for patients with node positive and non-metastatic BNET except for LCNEC, and may be harmful for patients with CT and NEC.

A randomised phase 2 study of 3 weekly cabazitaxel vs weekly paclitaxel chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer.

TPS1122 Background: Breast cancer (BC) represents 25% of all cancers in women. Whilst the majority have early stage disease approximately 30% will develop metastatic breast cancer (MBC). In HER2 negative MBC, palliative chemotherapy is one of the main treatment options. It remains to be seen whether the use of adjuvant taxane chemotherapy leads to an increase in taxane resistance at the onset of MBC, although for patients with a relatively short disease free interval this may be the case. Cabazitaxel (CBZ) is a novel taxoid selected for development from preclinical evidence in cell lines resistant to docetaxel and paclitaxel including activity in a HER-2 positive BC tumour xenograft, with innate resistance to docetaxel. Clinically CBZ is licensed for metastatic castration-resistant prostate cancer following progression during or after docetaxel chemotherapy. A phase 3 RCT in this patient group showed a 3 month overall survival benefit for patients receiving CBZ and prednisolone compared with mitoxantrone and prednisolone. Methods: CONCEPT is an open label randomised phase 2 trial of first line chemotherapy in patients with HER-2 negative MBC where paclitaxel would be considered the standard treatment. Patients are randomised to cabazitaxel 25 mg/m2 every 21 days for 6 cycles or paclitaxel 80 mg/m2 weekly for 18 weeks. Eligibility includes patients who are PS 0 or 1 who may have received prior docetaxel in the adjuvant setting or be taxane-naïve. The primary endpoint is progression free survival (PFS), defined as the time between the date of randomisation and progression (according to RECIST version 1.1) or death from any cause. Secondary end-points include safety, overall survival and assessment of quality of life factors by FACT-B and EQ-5D-5L. For the current phase 2 study 90 patients will be recruited, with a 1:1 randomisation, proceeding to phase 3 of 160 patients, if the interim analysis does not show futility. To date 38 patients have been recruited from 10 centres. The IDMC met in Oct 2016 and recommended the study continue recruitment.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

BackgroundCurrent guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. MethodsUsing the NCDB 2006–2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. Results3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). ConclusionAdjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS.

MP71-09 EFFECTIVENESS OF ADJUVANT CHEMOTHERAPY AFTER RADICAL NEPHROURETERECTOMY FOR LOCALLY ADVANCED AND/OR POSITIVE REGIONAL LYMPH NODE UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2017MP71-09 EFFECTIVENESS OF ADJUVANT CHEMOTHERAPY AFTER RADICAL NEPHROURETERECTOMY FOR LOCALLY ADVANCED AND/OR POSITIVE REGIONAL LYMPH NODE UPPER TRACT UROTHELIAL CARCINOMA Thomas Seisen, Ross E. Krasnow, Joaquim Bellmunt, Morgan Rouprêt, Jeffrey J. Leow, Stuart R. Lipsitz, Malte Vetterlein, Mark A. Preston, Nawar Hanna, Adam S. Kibel, Maxine Sun, Toni K. Choueiri, Quoc-Dien Trinh, and Steven Lee Chang Thomas SeisenThomas Seisen More articles by this author , Ross E. KrasnowRoss E. Krasnow More articles by this author , Joaquim BellmuntJoaquim Bellmunt More articles by this author , Morgan RouprêtMorgan Rouprêt More articles by this author , Jeffrey J. LeowJeffrey J. Leow More articles by this author , Stuart R. LipsitzStuart R. Lipsitz More articles by this author , Malte VetterleinMalte Vetterlein More articles by this author , Mark A. PrestonMark A. Preston More articles by this author , Nawar HannaNawar Hanna More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , Maxine SunMaxine Sun More articles by this author , Toni K. ChoueiriToni K. Choueiri More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , and Steven Lee ChangSteven Lee Chang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2265AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is limited evidence supporting the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with an overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. METHODS Within the National Cancer Data Base (2004-2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients in the two treatment groups. Additionally, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathological stage (pT3/T4N0, pT3/T4Nx and pTanyN+) and surgical margin status. RESULTS Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation after RNU, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC vs. observation (47.41[IQR,19.88-112.39] vs. 35.78 [IQR,14.09-99.22] months; P<0.001; Figure 1). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 43.90% vs. 35.85%, respectively. In IPTW-adjusted Cox regression analysis, AC was associated with a significant OS benefit (HR=0.77; 95%CI=[0.68-0.88]; P<0.001). This benefit was consistent across all subgroups examined (all P<0.05) and no significant heterogeneity of treatment effect was observed (all Pinteraction>0.05; Figure 2). CONCLUSIONS We report an OS benefit in patients who received AC vs. observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e948-e949 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Thomas Seisen More articles by this author Ross E. Krasnow More articles by this author Joaquim Bellmunt More articles by this author Morgan Rouprêt More articles by this author Jeffrey J. Leow More articles by this author Stuart R. Lipsitz More articles by this author Malte Vetterlein More articles by this author Mark A. Preston More articles by this author Nawar Hanna More articles by this author Adam S. Kibel More articles by this author Maxine Sun More articles by this author Toni K. Choueiri More articles by this author Quoc-Dien Trinh More articles by this author Steven Lee Chang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effectiveness of adjuvant chemotherapy after radical nephroureterectomy for locally advanced and/or positive regional lymph node upper tract urothelial carcinoma.

305 Background: There is limited evidence supporting the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with an overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Methods: Within the National Cancer Data Base (2004-2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients in the two treatment groups. Additionally, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathological stage (pT3/T4N0, pT3/T4Nx and pTanyN+) and surgical margin status. Results: Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation after RNU, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC vs. observation (47.41 [IQR, 19.88-112.39] vs. 35.78 [IQR, 14.09-99.22] months; P&lt; 0.001). The 5-year IPTW-adjusted rates of OS for AC vs. observation were 43.90% vs. 35.85%, respectively. In IPTW-adjusted Cox regression analysis, AC was associated with a significant OS benefit (HR = 0.77; 95% CI = [0.68-0.88]; P&lt; 0.001). This benefit was consistent across all subgroups examined (all P&lt; 0.05) and no significant heterogeneity of treatment effect was observed (all Pinteraction&gt; 0.05). The 3-month conditional landmark IPTW-adjusted analysis demonstrated little impact of immortal time bias (HR = 0.79; 95% CI = [0.70-0.91]; P = 0.001). Conclusions: We report an OS benefit in patients who received AC vs. observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

Abstract P5-14-02: Triple negative breast cancer - Adjuvant chemotherapy use and survival outcomes in Stage IA disease

Abstract Background: The potential benefit of adjuvant chemotherapy in patients with Stage IA triple negative breast cancer (TNBC) has not been defined. In general, patients with T1a and T1b lesions have not been included in adjuvant chemotherapy trials and the inclusion of T1c tumors has been limited. In this study using National Cancer Data Base (NCDB) we investigated the actual use of adjuvant chemotherapy in Stage IA TNBC patients relative to tumor size (T1a, T1b, T1c) and report their survival outcomes. Patients and Methods: Using NCDB we evaluated a cohort of 13,065 women with TNBC diagnosed between 2010-2012 who had American Joint Committee on Cancer Stage IA (node-negative with pathological T1a, T1b or T1c) tumors. Overall survival (OS) was the primary outcome variable. Based on the tumor size, patients were stratified on receipt of adjuvant chemotherapy or not. Patients were also stratified according to receipt of adjuvant radiation, radiation with boost, or none. Other adjusted variables included: age, race, Charlson comorbidity index, payer status, income, education, distance traveled, treating facility, and treatment delays. Multivariate Cox regression was employed to analyze the effect of adjuvant chemotherapy on overall survival. Results: The mean patient age for the entire cohort was 59.2 years (range 22-90 years), 55.8 years for the chemotherapy group, and 67.8 years for the non-chemotherapy group. There were 1275 T1a, 3197 T1b, and 7729 T1c patients. Tumor size was a very strong predictor of survival. Compared to T1a tumors, HR for death was 1.43 (95% CI: 0.86 –2.37) for T1b tumors and 3.00 (95% CI: 1.86 – 4.83) for T1c tumors. Out of all T1a, T1b, and T1c tumors in this cohort, 48.1 %, 72.6%, and 89.3% of patients received adjuvant chemotherapy respectively. A hazard ratio (HR) of death was 0.42 (95% CI: 0.31 – 0.57) for all patients who received chemotherapy compared to non-chemotherapy group. 4-year OS by tumor size and chemotherapy usage is listed in the table indicating an absolute increase of OS with adjuvant chemotherapy employment. HR for death was 0.90 (CI: 0.62 – 1.31) with use of radiation only and 0.67 (95% CI: 0.53 – 0.85) with use of radiation with boost when compared to no radiation therapy. 4-year OS (in percentage) with and without adjuvant chemotherapy use for node-negative T1a, T1b, and T1c TNBCTumor sizeNo ChemotherapyChemotherapyP ValueT1a93.78 %98.36 %0.146T1b91.91 %97.10 %&amp;lt;0.0001T1c80.62 %94.41 %&amp;lt;0.0001 Conclusion: NCDB indicated that the majority of patients with Stage IA TNBC received adjuvant chemotherapy, including 48% of patients with T1a lesions. Our data analysis demonstrated a statistically significant 4-year OS benefit in patients with T1b and T1c tumors who received adjuvant chemotherapy compared to those who did not. The survival benefit of adjuvant chemotherapy in patients with T1a tumors, however, did not reach statistical significance. Prospective randomized trials could define the potential benefits of adjuvant chemotherapy in patients with Stage IA TNBC, particularly for those with T1a and T1b tumors. Citation Format: Patel AN, Shi R, Peddi P, Burton GV. Triple negative breast cancer - Adjuvant chemotherapy use and survival outcomes in Stage IA disease [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-02.

Abstract P4-21-42: MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results

Abstract Background: MetaPHER investigates fixed-dose subcutaneous trastuzumab (Herceptin® [H SC]) in combination with intravenous (IV) pertuzumab (PERJETA® [P IV]) plus docetaxel (D IV). The MetaPHER study treatment regimen is based on CLEOPATRA (phase III; NCT00567190), which demonstrated a significant progression-free and overall survival benefit in patients (pts) with HER2-positive metastatic breast cancer (BC) following first-line treatment with IV trastuzumab (Herceptin® [H IV]) plus P IV plus D IV. Fixed-dose H SC was non-inferior to H IV in terms of pathological complete response and serum trough concentration, and had a comparable safety profile to H IV, in pts with HER2-positive early BC in HannaH (phase III; NCT00950300). Furthermore, PrefHer (NCT01401166) results showed compelling patient preference for H SC vs H IV (88.9% vs 9.6%) in the HER2-positive early BC setting. To date, limited data exist for H SC in combination with P IV and D IV; we report the first results of safety and tolerability from MetaPHER for this combination in pts with HER2-positive advanced BC. Methods: MetaPHER enrollment is ongoing at &amp;gt;100 sites in 12 countries. Females aged ≥18 years with metastatic or locally recurrent HER2-positive BC previously untreated with non-hormonal anticancer therapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, and left ventricular ejection fraction (LVEF) ≥50% receive fixed-dose H SC 600 mg/5 mL q3w, P IV (840 mg loading dose, then 420 mg at subsequent cycles q3w), and D IV (at least 6 cycles with a recommended initial dose of 75 mg/m2 q3w; possible escalation to 100 mg/m2 q3w and continuation of D IV after Cycle 6 at the investigator's discretion). Study treatment is given until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. The primary endpoint is safety and tolerability of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Adverse events (AEs) and serious AEs (SAEs) were graded per National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results are descriptive. Results: 150 pts were enrolled and received a median of 4 treatment cycles by the data cutoff date of June 23, 2016. Safety data are shown in the table. Pts with ≥1 event, n (%)H SC + P IV + D IV (N = 150)Any grade AEs136 (90.7)Grade ≥3 AEs59 (39.3)SAEs23 (15.3)Deaths2 (1.3)AEs leading to discontinuation of H SC, P IV, or D IV16 (10.7)AEs leading to discontinuation of H SC5 (3.3)AEs of Interest Administration-related and local injection-site reactions for H SC5 (3.3)*Cardiac: Grade ≥3 cardiac AEs†1 (0.7)Any grade congestive heart failure‡0Pts with a significant LVEF drop§1 (0.7)*Grade 1 &amp; 2 AEs only; †Events classified as System Organ Class Cardiac Disorders; ‡Preferred terms of reported AEs; §≥10% from baseline to LVEF &amp;lt;50%. Conclusion: MetaPHER's first report of H SC with P IV and D IV as first-line treatment for pts with HER2-positive advanced BC is consistent with the known safety profile for H IV with P IV and D IV from CLEOPATRA, and no new safety signals were identified. Citation Format: Kümmel S, Abraham J, Martin M, Crepelle-Fléchais A, Swat A, Nüesch E, Shing M, Tondini CA. MetaPHER phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer: First results [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-42.

Distinct Benefit of Overall Survival between Patients with Non-Small-Cell Lung Cancer Harboring EGFR Exon 19 Deletion and Exon 21 L858R Substitution

Background: Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial. Methods: The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R. Results: Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types. Conclusion: Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.

Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma.

Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 [interquartile range,19.88 to 112.39] v 35.78 [interquartile range, 14.09 to 99.22] months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 [95% CI, 0.68 to 0.88]; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all Pinteraction > .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

Impact of Baseline Characteristics on the Survival Benefit of High-Intensity Local Treatment in Metastatic Urothelial Carcinoma of the Bladder

A recent study reported an overall survival benefit for patients with metastatic urothelial carcinoma of the bladder (mUCB) managed with high-intensity local treatment (LT) of the primary tumor (chemotherapy plus radical cystectomy and/or radiation therapy ≥50Gy). Given the non-negligible morbidity of these procedures, adequate patient selection is crucial. Our objective was to identify patients who might benefit the most from high-intensity LT. Data for 3044 patients with mUCB at diagnosis were extracted from the National Cancer Data Base 2004–2013, and patients were categorized on the basis of treatment: high-intensity LT versus conservative LT (chemotherapy plus transurethral resection of bladder tumor and/or radiation therapy <50Gy). Multivariate Cox regression analysis predicted baseline 2-yr overall mortality (OM) risk among patients who received conservative LT. We then assessed the interaction between predicted OM risk and LT type. Compared to conservative LT, high-intensity LT yielded a higher observed OM-free survival rate among all patients with pure mUCB, irrespective of their predicted OM risk (nonsignificant interaction, p=0.7). These findings underline the need for further retrospective and prospective evaluation. Patient summaryAmong patients with metastatic histologically pure urothelial carcinoma of the bladder, we found an overall survival benefit of high-intensity local treatment directed at the primary tumor, regardless of predicted baseline 2-yr overall mortality risk.

Analysis of the Impact of KIR B Haplotype Donors on Outcomes after Haploidentical (HI) and Matched Related (MR) Hematopoietic Stem Cell Transplantation (HSCT)

Introduction:Natural killer (NK) cell alloreactivity has been associated with graft versus leukemia effects in HSCT. These effects are in part mediated through killer cell immunoglobulin-like receptors (KIR) on the surface of NK cells. The absence of inhibition of NK cells via inhibitory KIR in KIR ligand mismatched T-cell depleted HI HSCT, and the use of unrelated donors possessing activating KIR haplotypes (KIR-B) have been associated with improved overall survival (OS) due to relapse protection. Inhibitory KIR ligand mismatch in the setting of T-cell replete HI HSCT has not consistently been shown to be beneficial, and data regarding the impact of using KIR-B donors in T-replete HI and MR HSCT is limited. In this preliminary retrospective review, we compared outcomes between patients with KIR-B donors versus KIR A haplotype (KIR-A) donors after HI and MR HSCT to help inform donor selection.Methods:All patients underwent HSCT on our 2-step approach in which after conditioning, a fixed T cell dose (2 x 108/kg) is administered (step 1), followed 2-3 days later by cyclophosphamide (CY) for bidirectional tolerization. Two days after CY, patients receive a CD 34-selected donor product (step 2). To be included in the analysis, patients had to be alive for at least 1 month post HSCT and be without evidence of graft rejection. Recipients were divided into 2 groups based on whether they were transplanted from a KIR-B (possessing one or more non-framework activating KIR genes) versus a KIR-A donor (genotypically negative for non-framework activating KIR genes). The relationship between the use of a KIR-B donor and the end points of OS, relapse, grades II-IV acute graft versus host disease (GVHD), chronic GVHD and non-relapse mortality (NRM) was examined. Probability of OS was estimated by Kaplan-Meier (KM) method with log-rank analysis and multivariate analyses using Cox proportional hazards. Donor and recipient age and gender, HCT-CI score, Revised Disease Risk Index, presence of any inhibitory KIR ligand mismatch between donor and recipient and CMV reactivation after HSCT were considered as confounding variables. Cumulative incidence functions with competing risk analyses were used to estimate the probabilities of relapse, NRM, acute and chronic GVHD.Results:The study group consisted of 128 consecutive patients with myeloid malignancies (AML=91 MDS=27, CML=1, MPD=9) undergoing HI [n=84] or MR [n=44] HSCT. The median recipient age and follow-up of the study group was 58 (range 19-78) years and 40.6 (range: 1.07-117.27) months respectively. Only 13 (10.2%) patients had grade III or higher acute GVHD and only 7 (5.5%) patients developed severe, chronic GVHD (score of 3) respectively. Seventy-four (58%) and 54 (42%) of recipients had KIR-B versus KIR-A donors respectively. Fifty-five (74.3%) KIR-B donors possessed HLA C1 or C1/2 alleles in the presence of KIR2L2/3/2DS2. On multivariate Cox regression analysis, OS (HR, 0.579; 95% CI, 0.337-0.995; P= 0.048) was significantly higher in patients who received HSCT from KIR-B donors. On competing risk analysis, relapse (HR, 0.756; P=0.403) and NRM (HR, 0.466; P=0.128) were lower in patients who had KIR haplotype B donors though not statistically significant. In contrast, the risk of grades II to IV acute GVHD (with death as a competing event) was higher in patients with KIR-B donors (HR, 1.972; 95% CI, 1.009-3.852; P=0.047). Similarly transplants from KIR-B donors were associated with a higher risk of chronic GVHD (HR, 2.89; P=0.053).Discussion:Our results show that within the context of the 2-step approach, the use of a KIR-B donor is associated with improved OS and an increased risk of acute and chronic GVHD in patients with myeloid neoplasms receiving HI and MR HSCT. While not reaching significance, the results for relapse and NRM suggest that the OS benefit in patients with KIR-B donors was derived from a combination of lower relapse rates and NRM that was not adversely impacted by GVHD which was mostly lower grade in this population. Our findings support the concept of KIR-B donors as more alloreactive than KIR-A donors, specifically those possessing a C1-C1/2/2DL2/3/2DS2 repertoire, the primary type possessed by KIR-B donors in this analysis. The data argues for the continued use of KIR genotyping at our institution and analyses of HSCT outcomes based on donor KIR repertoire and other donor characteristics to optimize donor selection in HI and MR HSCT. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial

Durable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treated with Vosaroxin/Cytarabine Vs Placebo/Cytarabine: Updated Results from the Valor Trial

Assessment of Overall Survival Benefits in Patients Undergoing Complete Hepatectomy for Synchronous Colorectal Cancer With Liver and Lung Metastases.

Assessment of Overall Survival Benefits in Patients Undergoing Complete Hepatectomy for Synchronous Colorectal Cancer With Liver and Lung Metastases.