Greater Overall Survival Research Articles

Survival of Older Adults With Newly Diagnosed Acute Myeloid Leukemia: Effect of Using Multiagent Versus Single-agent Chemotherapy

BackgroundControversy exists regarding the optimal chemotherapy regimen for older adults with acute myeloid leukemia (AML). Patients and MethodsWe analyzed data from the US National Cancer Data Base of 25,621 patients aged 60 to 79 years, with a diagnosis of AML from 2004 to 2014, who had received single-agent versus multiagent chemotherapy. A Cox proportional hazard model was used for overall survival (OS) analysis for the entire study cohort and separately for patients who had received single-agent (n = 6743) versus multiagent (n = 6743) chemotherapy, matched for age, Charlson comorbidity index, and AML subtype. ResultsThe use of multiagent chemotherapy was high overall (70%) but declined with factors, such as increasing age, Charlson comorbidity index, AML subtype other than good risk, academic center, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had greater 1-year OS (43% vs. 28%), especially for patients aged 60 to 69 years and those with good-risk AML or Charlson comorbidity index of 0 to 1. OS (hazard ratio, 1.32; 95% confidence interval, 1.28-1.36) remained more favorable for the multiagent chemotherapy group on multivariable analysis. This was confirmed in a matched cohort analysis. ConclusionsTo the best of our knowledge, this is the largest real-world study that has demonstrated an association between factors such as age, comorbidity, and AML subtype and the use of multiagent chemotherapy. The use of multiagent chemotherapy was associated with improved OS, especially for patients aged <70 years, those with good-risk AML, and those with a low Charlson comorbidity index.

Abstract B05: Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC)

Abstract Background: Localized PDAC management has recently evolved. Due to concerns over micrometastases at diagnosis, the use of neoadjuvant chemotherapy for PDAC has become more common. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. Cancer antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A) has shown promising clinical data in a previously reported study in advanced PDAC (J Clin Oncol 2017;35:suppl 4S; abstract 341). We conducted a prospective, phase 2 clinical trial of patients with resectable, BR, and LA PDAC utilizing a regimen combining A + G + C + paricalcitol (P) with the primary endpoint of CA 19-9 normalization (NCT03138720). Methods: Eligibility criteria include patients with histologically confirmed resectable, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2, P at a fixed dose of 25 μg on days 1, 8 of a 21-day cycle (all treatment IV). Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate, and 2-year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date, 21 of the planned 24 patients have been enrolled: 11 male, 10 female; age range 49 to 85 yo. Patient classifications are 7 R; 7 BR; 7 LAPC. Most common drug-related grade (gr) 3-4 adverse events (AEs) are thrombocytopenia gr 3 40%, gr 4 33%, anemia gr 3 60%, and hypophosphatemia 13%. Of the 21, 16 are evaluable for maximum percent decrease in CA 19-9. CA 19-9 normalization occurred in 44% (7/16) who have completed at least 1 cycle of treatment. To date, 9 individuals went to surgery, with 8/9 achieving R0 (no pCR). Overall response rate in measurable patients is 26% (4/15 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with nonmetastatic PDAC, the use of A+G+C+P resulted in a CA 19-9 normalization rate in 44% of individuals. The study is ongoing and OS data are maturing. (Supported by grants from the HonorHealth Foundation and Marley Foundation.) Citation Format: Erkut Borazanci, Gayle Jameson, Courtney Snyder, Frank Tsai, Michael Gordon, Sunil Sharma, Carol Guarnieri, Amar Thosani, Syed Rahmanuddin, Ronald Korn, Steven Sckolnik, Paula Sedivy, Susan Haag, Kevin Gosselin, Daniel Von Hoff, Albert Amini. Paclitaxel protein bound plus gemcitabine plus cisplatin and paricalcitol neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC) [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B05.

Abstract B16: CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with 80% of patients succumbing within the first year and only 8% surviving &amp;gt;5 years. Responses are rare in later-line, metastatic PDAC trials. Thus, there is a clear unmet need to develop new treatment approaches guided by new and more accurate efficacy markers correlating with overall survival (OS) and not classical RECIST. SM-88 (racemetryrosine) used with methoxsalen, phenytoin, and sirolimus (MPS) has demonstrated effective reduction in circulating tumor cells (CTCs) in prostate and PDAC using multiple CTC assay variations. We now report OS associations. Method: Randomized phase II, multicenter, open-label prospective trial evaluating SM-88 in advanced PDAC. Ninety-nine patients were screened; 49 met inclusion criteria, with 38 evaluable per protocol. The trial evaluated overall survival, CTCs, PK parameters, and RECIST-determined response. Additional metabolism-related measures hypothesized to be impacted by SM-88s were also investigated (leptin, NLR, glucose, and others). CTCs were measured using a next-generation, microfluidic magnetic-based antibody detection method. Results: Preliminary results showed multiple efficacy measures correlated with overall survival. At baseline, in all evaluable patients (n=38, mean age 66yrs, approximately 80% having &amp;gt;2 prior lines) median CTCs were 110.8 CTCs/4mL, whereas those who achieved stable disease (SD) (n=4) and whose CTC levels decreased on SM-88 reported 123.2 CTCs/4mL at baseline. However, one patient who was a CTC responder and achieved a partial response (PR) had 13.3 CTCs/4mL at baseline. Patients with both an absolute and percent decrease from baseline in CTCs demonstrated greater OS using multiple threshold reductions; patients with &amp;gt;80% decrease or reduction in cell count to &amp;lt;50 CTCs/4mL demonstrated the strongest correlation with extended survival (p=0.18). Higher SM-88 Cmax (p=0.07) and AUC-6 (p&amp;lt;0.001) also correlated with OS. Based on RECIST, the clinical benefit rate (stable disease [SD] plus partial response [PR]) was 44%. There was a demonstrated survival advantage for patients who achieved SD (p&amp;lt;0.02). Females also achieved greater OS (p=0.01), which suggests the need for further clinical investigation. Metabolic measures of glucose levels (p=0.46) and leptin (p=0.28) did not appear to differ by sex. Conclusion: These data for SM-88 in PDAC illustrate that there are clear efficacy correlates with overall survival beyond traditional RECIST responses, including CTC measures. This may be of translational significance as the association between decreases in CTCs and overall survival had not been previously well documented prospectively in PDAC as compared to other tumor types. All together, these data are encouraging and warrant additional clinical investigation aimed at improving the dismal outcome of this malignancy. Citation Format: Marcus Smith Noel, Andrea Wang-Gillam, Allyson J. Ocean, Sant Chawla, Vincent Chung, Ron Korn, Giuseppe Del Priore, Vincent J. Picozzi. CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B16.

Comparison of outcomes between metaplastic and triple-negative breast cancer patients

PurposeMetaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. MethodsThe National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. ResultsAltogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS. ConclusionsMBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein.

Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation

BackgroundUncommon epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a rare subset of NSCLC. The aim of this study was to investigate the prevalence, characteristics, and clinical outcomes of metastatic NSCLC harboring uncommon EGFR mutation at Thailand’s largest national tertiary hospital. The secondary objective was to compare treatment efficacy between EGFR-tyrosine kinase inhibitor (EGFR-TKI) and chemotherapy.MethodsThis retrospective chart review included patients that were tested for EGFR-mutation NSCLC during 2014–2018. Patient demographic and clinical data, treatment data, and outcome data were collected and analyzed.ResultsOf the 681 patients that were evaluated for EGFR mutation, 317 (47.0%) had EGFR-mutant NSCLC, and 28 (8.8%) of those harbored uncommon EGFR mutations. The median follow-up was 19.1 months. History of tobacco use was reported in 50% of patients. The most common single mutation among uncommon EGFR was exon 20 insertion (n = 6), followed by L861Q (n = 5) and G719X (n = 4). Thirteen (46%) patients had compound mutations. One hundred percent of male patients with G719X mutation were smokers. Sixteen of 28 patients were treated with EGFR-TKI. Most received first-generation EGFR-TKI, and 29% were treated with chemotherapy alone. The objective response rate was 37.5% in the EGFR-TKI group. Median progression-free survival (PFS) in the EGFR-TKI group was 10.2 months. Median PFS among the 8 patients in the chemotherapy group that received first-line platinum doublet was 6.5 months. Three-year overall survival (OS) among 28 patients was 34%. Three-year OS was significantly better in patients treated with EGFR-TKI.ConclusionsUncommon EGFR mutations was detected in 8.8% of EGFR-mutant NSCLC. Exon 20 insertion was the most common mutation, and 50% of patients had history of tobacco use. First- or second-generation EGFR-TKI demonstrated greater OS benefit than platinum-doublet chemotherapy among patients harboring uncommon EGFR-mutant NSCLC. Survival outcomes were comparable to those reported from previous large cohort studies.

Abstract 4992: The occurrence of immune-related adverse events indicates better efficacy of immune checkpoint blockade in solid tumors: A systematic review and meta-analysis

Abstract Introduction: Immune-related adverse events (irAEs) were mostly induced by immune checkpoint blockade (ICB) and were associated with the immune response. Whether irAEs are associated with clinical benefits during ICB treatment in cancer patients remains unclear. This systematic review and meta-analysis aimed to investigate the relationship between irAEs and clinical efficacy. Methods: We systemically searched and selected irAEs and clinical outcome data from cancer patients treated with ICB in the PubMed, Embase, and Cochrane Central Trial databases up to July 26, 2018. Keywords used for the search included PD-1, PD-L1, CTLA-4, immune checkpoint and immune-related adverse events. The relationships between the occurrence of irAEs and the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were assessed using relative risk (RR) or hazard ratio (HR) values and 95% confidence intervals (CIs) in random-effect models. Results: Nineteen eligible observational articles were included in this systematic review and fourteen studies including 3022 participants (1264 with irAEs and 1758 with non-irAE) were included in our meta-analysis. The occurrence of irAEs was significantly associated with higher ORR (RR = 2.36, 95% CI: 1.85-3.02; P &amp;lt; 0.001), better PFS (HR = 0.48, 95% CI: 0.26-0.70; P &amp;lt; 0.001), and longer OS (HR = 0.42; 95% CI = 0.18-0.67; P = 0.001) than those in the non-irAE group. Subgroup analysis showed that the effect size of ORR in anti-PD-1 therapy (RR = 2.68, 95% CI, 2.21-3.26) was inferior to that of the anti-CTLA-4 therapy (RR = 1.91, 95% CI, 0.44-8.32). The meta-regression models also found that ICB type (anti-CTLA-4 or anti-PD-1) were associated with significant heterogeneity (P = 0.005). Conclusion: In conclusion, irAEs indicate greater ORR, PFS and OS than non-irAEs in ICB treatment, and the relationship in anti-PD-1 therapy was stronger than in anti-CTLA-4 therapy. With appropriate management of irAEs, the clinical predictor, continued treatment may be possible to maximize its potential ICB benefits. Note: This abstract was not presented at the meeting. Citation Format: Xu Yang, Dongxu Wang, Jianzhen Lin, Jianping Xiong, Junyu Long, Yi Bai, Jin Bian, Hanchun Huang, Xiaobo Yang, Yilei Mao, Xinting Sang, Haitao Zhao. The occurrence of immune-related adverse events indicates better efficacy of immune checkpoint blockade in solid tumors: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4992.

Predictive factors for the benefit of triple‐drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma

BackgroundCompared with single‐drug TACE, our previous phase III study demonstrated that triple‐drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single‐drug TACE.MethodsPatients in the triple‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single‐drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center.ResultsNo difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple‐drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single‐drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple‐drug chemotherapy benefit versus single‐drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller).ConclusionsTriple‐drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single‐drug TACE.

Challenging AJCC 8 Staging for Soft Tissue Sarcoma Using the NCDB

To determine whether the new American Joint Committee on Cancer (AJCC) 8 grouping of soft tissue sarcoma (STS) with nodal disease (N1M0) and metastatic disease (M1) as stage IV correctly represents the prognosis of these previously separate patient groups, using the National Cancer Database. Adults with STS identified in the 2004 to 2014 National Cancer Database, classified by the World Health Organization 2013 system into 10 histologic subgroups, were grouped according to AJCC 8 staging and analyzed according to demographic characteristics, histology, primary site, disease extent, and adjuvant treatment. Primary retroperitoneal sites, "other/unusual" histologic subgroups, and those with delays in therapy (>180 days from diagnosis) were excluded. We used χ2 tests, Cox proportional hazard models, and propensity-score matched analyses. Of 82,987 patients identified, 55,417 met inclusion criteria; 29,855 (53.9%) were male, and 25,262 (46.1%) were female. Median age was 60 years (range, 18-90 years). Overall survival (OS) of STS of all sites was significantly different between N1M0 and N0-1M1 patients at 5 years (34.4%; [95% confidence interval {CI}, 30.1%-38.8%] vs 10.1% [95% CI, 9%-11%], respectively) and 10 years (27.3% [95% CI, 22.5%- 32.2%] vs 5.4% [95% CI, 4.5%-6.5%], respectively; log-rank test, P < .001). For STS of trunk and extremities in N1M0 and N0-1M1 patients, the N1M0 cohort was associated with significantly greater OS on multivariate Cox proportional hazards models (hazard ratio, 0.48; 95% CI, 0.41-0.58; P < .001), and this OS difference remained significant for propensity-matched cohorts of all primary sites (HR, 0.53; 95% CI, 0.44-0.64; P < .001). In adult STS, including those of the trunk and extremity, OS is superior with N1M0 compared with N0-1M1 disease. These results suggest that the AJCC 8th edition grouping of N1 and M1 patients into stage IV may obscure the more favorable prognosis of patients with N1M0 disease.

Surrogate end points for overall survival in patients with advanced non-small-cell lung cancer in trials of immunotherapy.

e14122 Background: Our objective was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate end points for overall survival (OS) among patients with advanced non-small-cell lung cancer (NSCLC) in randomized trials of immunotherapy. Methods: Individual patient data (total N = 569 patients) were available from two multicentre, randomized, phase II/III trials (POPLAR and OAK). Analysis of OS, PFS and ORR were computed using the Kaplan-Meier estimates method and compared with the log-rank test, hazard ratios [HRs] and 95% confidence intervals [CIs] were calculated by using the Cox regression model. The surrogacy was evaluated using Spearman’s correlation coefficient (ρ) and coefficient of determination ( R²) between treatment effects on the surrogate end point and OS. We further validated the surrogacy in trial-level analysis with 26 NSCLC immunotherapy trials (total N = 12,094 patients) published prior to June 2018. Results: In the patient-level analyses, patients who achieved a response had better OS compared with nonresponders (HR 0.18; 95% CI, 0.11 to 0.29; P &lt; 0.001). Greater OS was also observed in landmark anlyses at 6-month PFS (HR 0.21; 95% CI 0.11 to 0.39; P &lt; 0.001) and 12-month PFS (HR 0.16; 95% CI 0.11 to 0.24; P &lt; 0.001). PFS correlated with OS at the individual level (Spearman ρ = 0.37; P &lt; 0.001). In the trial-level analysis, PFS moderately correlated with OS (Spearman ρ = 0.64; P &lt; 0.001), and the R² was 0.50 (95% CI 0.39 to 0.64). Conclusions: In NSCLC immunotherapy trials, responders and patients with longer PFS had better OS. ORR and PFS are acceptable surrogates for OS in trials of immunotherapy, but caution must be taken when interpreting efficacy in the absence of OS data.

Prediction of metastatic castrate-resistant prostate cancer response to abiraterone or enzalutamide by a baseline blood-based CTC gene expression signature.

e16529 Background: Prostate cancer is the most common cancer in men in the U.S., with 30% 5-year overall survival (OS) for patients (pts) with metastases. To take a precision medicine approach to the management of metastatic castrate-resistant prostate cancer (mCRPC), we developed a blood circulating tumor cell (CTC)-based test to identify mCRPC pts most likely to benefit from abiraterone (abi) or enzalutamide (enza). Methods: In this multi-institution prospective study, men with mCRPC were enrolled prior to starting abi (1,000 mg/d plus prednisone 10 mg/d) or enza (160 mg/d). At baseline (BL), 12 w, and progression, blood samples were collected for CellSearch-based CTC enumeration and qPCR-based gene expression analysis. Results: 69 pts (median age 68 y [50-82]) received abi (n = 25) or enza (n = 44) and had evaluable blood samples. Consistent with prior publications, among 43 pts with BL CTC &gt; 0, clearance of detectable CTCs (BL CTCs &gt; 0 and 12 w CTCs = 0), was achieved in 24 patients (55.8%), and was associated with greater median OS (31 mo vs. 18 mo, log-rank p = 0.03). The 43 pts with BL CTC &gt; 0 were then randomly divided into training (n = 31) and validation (n = 12) sets. Baseline gene expression data for the training set was used to develop a model to predict CTC clearance, starting with a panel of 141 expressed genes/isoforms including those associated with prostate cancer. Of the models tested, random forest yielded the best performance, with respective training and validation set sensitivity of 0.7 and 1, specificity 0.75 and 0.71, AUC 0.88 and 0.91. Top genes identified include those previously associated with disease – HOXB13, ESRP2, KLK3, GRHL2, and KRT19, among others. Conclusions: A gene expression signature from a baseline blood sample with CellSearch-enriched CTCs can predict clearance of detectable CTCs in response to abi/enza with high AUC and may give insight into molecular mechanisms of response. A prospective study with a larger number of patients will be required to further validate our findings. Ultimately, this blood test has the potential to select the patients most likely to benefit from second-generation antiandrogen vs. non-hormonal systemic treatment.

Defects in DNA repair genes and long-term survival in cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC).

4536 Background: Although cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in MIBC, only a subset of patients have pathologic complete response (pT0) at cystectomy. ATM, RB1 and FANCC mutations have shown correlation with pT0 to cisplatin-based NAC, as previously published. We now report updated OS and disease specific survival (DSS) from two phase II trials using these gene alterations as biomarkers. Methods: Patients with stage T2-T4 (N0 or N1) MIBC were enrolled in phase II trials of dose-dense NAC with MVAC (methotrexate, vinblastine, adriamycin, and cisplatin; NCT01031420) or GC (gemcitabine and cisplatin; NCT01611662). Patients were treated with NAC with plan for curative cystectomy. DNA from pretreatment tumor tissue was sequenced for coding exons of 287 cancer-related genes and analyzed for mutations. Survival in patients with one or more mutations in ATM, RB1, or FANCC genes was compared to those without mutations. Results: Of 58 pts treated, 38% (22/58 pts) had relevant mutations in the combined group of MVAC (13/34 pts) and GC (9/24 pts) trials. At a median follow-up of 56 months and minimum follow up of 16 months, patients with mutations had statistically significantly greater OS (p = 0.0043) and DSS (p = 0.0015). Median OS/DSS was not reached for patients with a mutation in any group. At 5 years post treatment, OS/DSS were greater in mutated vs non-mutated patients in all groups (see table). Conclusions: Long-term follow up reveals that previously reported improved responses to cisplatin-based NAC associated with mutations in ATM, RB1 and FANCC also confer a clinically meaningful and statistically significant survival benefit in these patients. These alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients most likely to benefit from NAC prior to radical cystectomy. [Table: see text]

Prognostic value of monocyte to lymphocyte ratio (MLR) in epithelial ovarian cancer (EOC).

e17066 Background: Identifying high-risk early-stage EOC patients (p) is a major issue. Also, controversy about the role of neoadjuvant chemotherapy prior to surgery in advanced EOC is still ongoing. A high MLR is related to poorer outcomes in several cancers, and also in ovarian cancer according to limited retrospective series. We explored the clinical value of MLR in a cohort of EOC p. Methods: We included all EOC p diagnosed in our center, from January 2008 to April 2017, who had undergone radical treatment. Overall survival (OS) was assessed by Kaplan Meyer. Maximally selected rank statistics was used to determine the MLR cut-off value for the greatest OS discrimination. The hazard ratio (HR) of death of MLR was explored by multivariate Cox regression models, adjusted by age at diagnosis, stage I/II versus (vs) III/IV, high grade serous carcinomas (HGSC) vs other, primary surgery vs interval surgery after neoadjuvant chemotherapy (PS, IS), residual disease &lt; 1 vs &gt; 1cm, year of diagnosis, and hemoglobin, neutrophils, platelets and MLR at diagnosis. Results: 124 p were included. Median age at diagnosis was 58.7 years; 55.6% were HGSC;67.7% stage III/IV; 69.3% received PS; 14.3% had residual disease &gt; 1cm. Median OS was 75 months. MLR was the laboratory parameter that more significantly impacted on OS in our model (p = 0.02). Optimal MLR cut-off was 0.38. The MLR &gt; 0.38 group (MLR-hi) had a higher-risk of death (HR = 2.9; 95% IC: 1.3–6.5) with respect to those with MLR &lt; = 0.38 (MLR-lo). Median OS were 100 and 35 months, respectively. In the MLR-lo group, median age at diagnosis was 56.9 years (vs 61.9 in the MLR-hi, p 0.047), 44.8% were HGSC (vs 61.2%, p 0.134), and 49.97% were stages I/II (vs 14.2%, p 0.001). MLR-hi p who had undergone PS or IS had similar OS (p = 0.63). In contrast, among MLR-lo p, PS showed significantly higher OS than IS (p &lt; 0.0001). Conclusions: In our cohort, MLR was an independent prognostic factor in EOC. Its potential role to identify high-risk early-stage p and to predict worse outcomes after PS among advanced-stage p need to be explored in larger cohorts.

Treatments and outcomes of spinal metastasis from thymic epithelial tumors: 10-year experience with 15 patients in a single center.

Although thymic epithelial tumors (TETs) are rare, their spinal metastases are even rarer, and they have only been described in a few case reports. The aim of the present study is to discuss the possible treatments and outcomes of patients with spinal metastasis from TETs. Included in this retrospective study were 15 patients with metastasis of TETs who received either radical or debulking surgery plus radiochemotherapy as adjuvant therapy in our center between 2007 and 2017. Possible prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by log-rank analysis. Our series comprised seven men and eight women, with a median age of 52years. The period from the primary diagnosis to spinal metastasis varied from 0 to 16months. The metastatic lesions were mainly located in the thoracic spine (n = 11; 73.3%), followed by the cervical and lumbar spine (n = 2; 13.3%, respectively). The median follow-up period was 28months. Local tumor progression was detected in four patients (26.7%), and seven patients (46.7%) died of the disease during the follow-up period. Log-rank analysis indicated that radical resection was associated with longer PFS, whereas PFS, response to systemic chemotherapy and WHO B1-B2 were favorable factors of OS for patients with spinal metastatic TETs. Radical surgery is associated with longer PFS, while PFS is associated with better OS. Postoperative radiotherapy seems to be a useful supplementary treatment after debulking surgery, and patients who respond to postoperative chemotherapy were demonstrated with greater OS. WHO type B3-C seemed to be an adverse factor for spinal metastasis from TETs. These slides can be retrieved under Electronic Supplementary Material.

Androgen decline and survival during docetaxel therapy in metastatic castration resistant prostate cancer (mCRPC).

Background:Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS.Methods:Data from 1,050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors.Results:Median baseline values for T, A, and, DHEA were 1.0, 13.5 and 8.1, ng/dL respectively while 6 week levels were 0.64, 7.0 and 6.8, ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI=1.01–1.03, p=0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ≥50% decline in PSA with an odds ratio of 0.93 (95% CI=0.85–0.98, p-value=0.039).Conclusions:Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

The influence of sex on the prognostic value of body mass index in non-metastasis renal cell carcinoma.

Purpose: The prognostic value of obesity in patients with renal cell carcinoma (RCC) remains controversial. This study aimed to assess the sex-dependent prognostic role of body mass index (BMI) in patients with nonmetastatic RCC who underwent radical or partial nephrectomy.Patients and methods: We retrospectively analyzed 643 consecutive patients with nonmetastatic RCC who underwent curative nephrectomy in our center between 2004 and 2014. Associations among BMI, sex, overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were analyzed.Results: Males were more likely to have a higher BMI than females (BMI as a categorical variable: P<0.001; BMI as a continuous variable: P=0.002). In men, a high BMI was significantly correlated with better 5-year OS, CSS, and MFS rates (P=0.001, 0.014, and 0.001, respectively), and multivariate analysis identified that a high BMI was independently associated with greater OS, CSS, and MFS (OS: hazard ratio [HR]=0.207, P=0.011; CSS: HR=0.225, P=0.005; MFS: HR=0.243, P=0.004). However, in women, there was no significant difference in 5-year OS, CSS, and MFS rates according to BMI (P=0.781, 0.812, and 0.538, respectively). Moreover, a high BMI was no longer independently associated with OS, CSS, or MFS (P=0.821, 0.832, and 0.801, respectively). Among patients with clear cell RCC, BMI was significantly associated with OS, CSS, and MFS only among men (all P<0.05) and not among women (all P>0.05).Conclusion: Among patients with nonmetastatic RCC, a high BMI was a favorable prognostic factor in males rather than females. Therefore, sex might influence the correlation between obesity and urological outcomes in nonmetastatic RCC.

Outcomes of nivolumab (NIVO)-treated patients (pts) with advanced non-small cell lung cancer (aNSCLC) in United States community oncology practice.

119 Background: The phase 3 Checkmate 017 and 057 trials demonstrated improved survival of NIVO vs. chemotherapy in pts who progressed on or after platinum-based chemotherapy for aNSCLC, regardless of histology (squamous [SQ]/non-squamous [NSQ]) and PD-L1 expression. Real-world (RW) long-term effectiveness data with PD-1 inhibitors are limited. This study evaluated RW adoption of I-O and outcomes of NIVO-treated pts with aNSCLC in community practices, overall and by histology. Methods: This retrospective observational study of US Oncology Network electronic health records and supplemental chart abstraction followed a cohort of pts with aNSCLC receiving PD-1 inhibitors for ≥17 months, from initial FDA approval, 03/2015 through 10/2017. Pts in clinical trials or receiving treatment for other malignancies were excluded. Demographic and clinical features were characterized. Duration of therapy (DOT) and overall survival (OS) were assessed by the Kaplan-Meier method. Results: Of 217 included pts, 203 received NIVO; outcomes for 14 receiving pembrolizumab are not presented. NIVO was administered as first-line (1L) therapy in 15 pts, 2L+ therapy in 188 pts (n = 134 LOT2, n = 54 LOT3-4). For all 2L+ pts treated with a PD-1 inhibitor, median age was 70 years, 57% were male, 73% had NSQ histology, and 82% had ECOG performance status of 0-1. All pts with biomarker data were ALK negative and 5% were EGFR positive. Approximately 13% of pts had PD-L1 testing, of whom 6% were positive (expression &gt; 1%). For 2L+, DOT (median months [mos], 95% CI) was 3.5 (3.0, 4.1) in the overall population, 3.3 (1.9, 4.2) with SQ, and 3.6 (2.3, 4.6) with NSQ histology. Of all 2L+ pts, 30.3% (95% CI 23.9%, 37.0%) remained on treatment at 6 mos. For 2L+, OS (median mos, 95% CI) was 8.7 (7.6, 11.0) overall, 7.0 (3.8, 9.1) with SQ, and 10.5 (8.4, 13.3) with NSQ histology; 1-year OS was 35%. Conclusions: RW DOT and OS for 2L+ NIVO treatment of aNSCLC were similar to outcomes reported in the phase 3 Checkmate 017 and 057 trials, with longer DOT and greater OS in patients with NSQ histology. Few RW pts had PD-L1 testing in this 2L+setting. Future analyses are needed to assess the uptake of PD-1 inhibitors for 1L treatment of aNSCLC.

Interpreting survival outcomes for African-American (AA) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T (SIP-T) with number needed to treat to benefit (NNTB).

222 Background: AA men often present with more aggressive prostate cancer and are less likely to receive treatment, negatively affecting quality-of-life and overall survival (OS). Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. Data from the PROCEED registry showed that OS for AA pts treated with SIP-T was 9.3 mo longer than OS for Caucasian pts. In a prior subgroup analysis of Phase III data, AA pts realized a 30.7-mo difference in OS with SIP-T vs. placebo (PBO). We calculated the NNTB to further interpret the OS benefit in AA pts. Methods: Data were pooled from 3 Phase III mCRPC SIP-T trials (D9901, D9902A, and IMPACT). The absolute risk reduction (ARR) is calculated from Kaplan-Meier estimates at 12-, 24-, and 36-mo for all SIP-T subjects, and an AA cohort, receiving ≥1 infusion. NNTB, the inverse of the ARR, represents the number of pts needed to be treated with SIP-T to prevent 1 additional death compared to PBO. All NNTB values are rounded up. Results: Of the 737 pooled mCRPC pts enrolled, 488 men were randomized to SIP-T (n=33 AA), and 249 to PBO. Baseline clinical characteristics between the SIP-T and PBO groups were well balanced; however, compared to overall SIP-T and PBO, AA SIP-T pts were more likely to have received prior chemotherapy, lower hemoglobin, and better performance status. The NNTB at 12-mo was the same (13) for both the pooled SIP-T and AA treated cohort. At 24-mo, the NNTB values were 10 for pooled and 5 for AA. At 36-mo, an NNTB of 8 (pooled) and 3 (AA) SIP-T treatments prevented 1 additional death (Table). Conclusions: This NNTB analysis shows a favorable survival benefit for AA men treated with SIP-T and all treated SIP-T subjects. NNTB values declined over 3-years, suggesting durability of clinical benefit with SIP-T, and that it may address a known survival disparity in AA with prostate cancer. Studies with larger sample sizes may confirm if AA pts derive a greater OS benefit from SIP-T. Clinical trial information: NCT00065442. [Table: see text]

Treatment facility volume and survival in patients with advanced prostate cancer.

274 Background: Despite improvements in the medical management of advanced prostate cancer (aPC), it continues to be the 2nd leading cause of cancer death in American men. The contemporary management of men with aPC is increasingly complex and can vary based on access to up-to-date treatments, which is often found at busier treatment centers. We thus evaluated the relationship between facility volume and survival outcomes in aPC. Methods: The National Cancer Database (NCDB) was queried from 2004-2014 for aPC, defined as T4, N+, or M+ disease. Six pre-defined patient cohorts were evaluated. Cohort A = patients with aPC (N = 64,815); cohort B = M0 patients (N = 27,155); cohort C = M0 patients undergoing active treatment (N = 21,755); cohort = all M1 patients (N = 37,660); cohort E = M0 patients undergoing active treatment (N = 30,643); and cohort F = M1 patients who underwent active treatment and who had known metastatic sites (N = 12,452). Treatment facilities were divided into quartiles based on median treatment volume: &lt;1.8 patients/year, 1.8-3.3 patients/year, 3.4-5.6 patients/year, and &gt;5.6 patients/year. Regression models were adjusted along a set of covariates available in the NCDB. The primary outcome was overall survival (OS). Results: OS improved with each increase in volume quartile. The top quartile (&gt;5.6 pts/yr) demonstrated significantly greater OS compared to the bottom quartile (&lt;1.8 pts/yr) [HR 0.82, 95% CI 0.77-0.88, p&lt;0.001]. The improved OS in the top volume quartile remained consistent when analyzed across the six pre-defined patient cohorts. Sensitivity analyses were conducted on Cohort A, adjusting for Gleason score and facility type, which did not change the effect of volume on survival. Conclusions: In this retrospective analysis of nearly 65K men who presented with aPC, we demonstrate that management at a high-volume facility (top quartile, &gt;5.6 pts/yr) confers a significant OS advantage when compared to management at a facility in the lowest quartile (&lt;1.8 pts/yr). This OS advantage persisted with similar magnitudes of effect after narrowing the cohorts by disease and treatment characteristics. These findings may have implications on the optimal management of men with advanced PC.

Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry.

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.

Efficacy of Radiofrequency Ablation versus Transarterial Chemoembolization for Patients with Solitary Hepatocellular Carcinoma ≤3 cm

Optimal treatment for small hepatocellular carcinoma (HCC) ≤ 3 cm remains controversial. Ablation and chemoembolization are considered for nonoperative candidates. This study compares survival among patients with solitary HCC ≤ 3 cm treated with radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Patients diagnosed with HCC ≤ 3 cm between 2005 and 2014 were included. Kaplan-Meier survival functions with log-rank tests were used to estimate recurrence-free survival and overall survival (OS) survival. Among 161 patients with solitary HCC ≤ 3 cm, 145 patients with mean age of 65.2 years (±9.2) and 95 per cent prevalence of cirrhosis had operative treatment or TACE, and/or RFA. From this cohort, 27 (19%) patients had TACE, 27 (19%) patients had RFA, and 15 (10%) patients had TACE/RFA. The patients treated with definitive TACE, RFA, or TACE/RFA had a similar 1-year recurrence-free survival (23% vs 27% vs 36%, respectively, P = 0.445) and similar 5-year OS (21% vs 24% vs 33%, respectively, P = 0.287). Thirty-five (24%) patients were bridged to transplantation with TACE and/or RFA. The 5-year OS was significantly improved in patients bridged to transplantation (P < 0.001). Survival does not differ between patients with solitary HCC ≤ 3 cm treated with TACE or RFA. Patients who were bridged to transplantation had significantly greater OS compared with patients who were not transplanted.