Baseline Eastern Cooperative Oncology Group Performance Status Research Articles

Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients with Advanced Illness.

We evaluated the impact of baseline patient characteristics on safety and efficacy of methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, in patients with advanced illness with opioid-induced constipation (OIC). This analysis pooled data from 2 randomized, double-blind, placebo-controlled studies (study 302: NCT00402038; study 4000: NCT00672477) in patients with advanced illness, including cancer, and OIC. Patients were randomized to receive subcutaneous methylnaltrexone (study 302: 0.15 mg/kg; study 4000: 8 or 12 mg based on weight) or placebo every other day for 2 weeks. The proportions of patients achieving rescue-free laxation within 4 or 24 hours after the first dose of study drug were assessed in patient subgroups stratified by baseline age, Eastern Cooperative Oncology Group (ECOG) performance status, cancer status, laxative type, and opioid requirement. Treatment-emergent adverse events (TEAEs) were evaluated. Overall, 363 patients were included in this analysis (methylnaltrexone, 178; placebo, 185). Mean (SD) age was 66.3 (13.7) years and 48.5% were men overall. A significantly greater proportion of patients receiving methylnaltrexone versus placebo achieved rescue-free laxation within 4 hours (111/178 [62.4%] vs 31/185 [16.8%]; P<0.0001) and 24 hours (135/178 [75.8%] vs 81/185 [43.8%]; P<0.0001) of the first dose. These trends were consistent across all subgroups. Most patients experienced ≥1 TEAE in the overall population (methylnaltrexone, 82.1%; placebo, 76.2%), which remained consistent when stratified by baseline characteristics. More than half of TEAEs were gastrointestinal in nature. Abdominal pain was more common in patients receiving methylnaltrexone than placebo across baseline characteristic subgroups. Methylnaltrexone treatment was superior to placebo in achieving rescue-free laxation within 4 and 24 hours after the first dose, irrespective of patients' cancer status, baseline ECOG performance status, or baseline opioid or laxative use. The methylnaltrexone safety profile remained consistent across baseline characteristic subgroups.

Neoadjuvant chemotherapy followed by definitive chemoradiation in technically unresectable oral cavity squamous cancers.

e18073 Background: Definitive Chemoradiation has dismal outcomes in very advanced oral cavity cancers. Surgical resection is the preferred modality of treatment . NACT followed by assessment for surgery is the standard algorithm used in technically unresectable oral cavity squamous cancers. Patients who are not amenable for surgery or not willing for the same are subjected to definitive Chemoradiation. There is very limited data about the outcomes of these patients and hence we have performed this analysis. Methods: This is an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable oral cavity squamous patients who received NACT. Adults patients with an eastern co-operative oncology group (ECOG) performance status (PS) 0-2 who were deemed as technically unresectable in a multi-disciplinary clinic (MDC) were included. These patients received 2-3 cycles of NACT (3-weekly) and underwent a response assessment. Depending on response and general condition, they were re-assessed in MDC and further therapy was decided. Patients who were not amenable to surgery and not willing for the and considered for definitive Chemoradiation were included in this analysis. Overall survival (OS) was calculated from date of diagnosis to date of death. Kaplan-meier method was used for estimation of 5 years OS. Impact of response to neoadjuvant chemotherapy on overall survival was calculated using log-rank method. Results: A total of 429 patients were analysed of which 387 (90.2%) were males The median age was 40 years (IQR; 40-54 years). The baseline ECOG PS was 0 in 163 (38%), 1 in 257 (59.9%) and 2 in 9 (2.1%) patients. The clinical stage at presentation was IVA in 257 (59.9%) patients and IVB in 172 (40.1%). The neoadjuvant regimen received were TPF regimen in 162 (37.8%) patients and two drug Taxane- Platinum regimen in the rest. The response rate to neoadjuvant therapy was 35.9% (N=154). Three thirty nine patients had an event with a median survival of 10 months (95%CI-;8.6-11.4). The five year survival was 15.6 % (Standard error 2%), while the 10 year OS was 9.6% (standard error 2.6%). On multivariate analysis, the only factor impacting the OS was response to neoadjuvant chemotherapy (HR: 0.54, 95% CI; 0.43-0.69; P=0.000). Conclusions: Neoadjuvant Chemotherapy followed by definitive Chemoradiation (who are not amenable for surgical resection or not willing) leads to dismal outcomes and further strategies to improve the outcomes are warranted.

Clinician-Based Performance Status and Its Correlation with Patient-Reported Outcomes: Findings from a Prospective Observational Study in Patients with Mantle Cell Lymphoma

Clinician-Based Performance Status and Its Correlation with Patient-Reported Outcomes: Findings from a Prospective Observational Study in Patients with Mantle Cell Lymphoma

Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?

AbstractFunctional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS > 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients' vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies.

The relationship between Eastern Cooperative Oncology Group performance status and healthcare resource utilization among patients with advanced or metastatic colorectal, lung or gastric cancer

Aims The ability of a patient to receive anti-cancer treatment depends on a variety of factors, including performance status (PS), which is typically measured using the Eastern Cooperative Oncology Group (ECOG) scale. This study hypothesized that there would be a strong and positive correlation between ECOG PS values and healthcare resource utilization (HCRU) and a strong and negative correlation with the use of anti-cancer therapy. Materials and methods Patients with colorectal, lung or gastric cancer were included in this retrospective analysis of administrative claims data linked to electronic medical records (EMR). All-cause HCRU (hospitalization/inpatient care, emergency room visits, systemic anti-cancer therapy, radiation therapy, outpatient physician visits, hospice, home health care and key supportive care treatments such as anti-emetics, hematopoietic treatments, transfusions, and durable medical equipment) was evaluated by baseline ECOG PS value and PS over time. Adjusted multivariable regression analysis was used to assess the relationship between baseline ECOG PS and HCRU. Regression analyses were conducted to explore the relationship between other baseline variables and HCRU. Results There were 1311 patients included in this study. There was low correlation between PS and any HCRU variable or receipt of anti-cancer therapy (correlation coefficients all <0.10). In regression analyses, the proportion of patients with poor PS (PS = 2+) who were hospitalized was not significantly different from those with good PS (PS = 0/1) (28.9% versus 19.3%, p = .07). Limitations The low rate of reporting of PS and the small sample size of patient groups in this study. Conclusions There is very little evidence of a relationship between ECOG PS and HCRU, ECOG PS, or anti-cancer therapy in this study, in part due to low rates of and lack of variability in reported PS. There is some evidence that baseline comorbidities were significantly associated with HCRU and should be accounted for in future research evaluating HCRU.

Continuous monitoring of mobility performance trajectory in patients receiving chemotherapy.

e14104 Background: Accurate performance status (PS) assessment is important for chemotherapy decisions, but current tools such as the Eastern Cooperative Oncology Group (ECOG) PS assessment are subjective, static, and prone to inter-observer and recall biases. Continuous patient monitoring technology can enhance PS assessment by providing an objective and dynamic measurement of mobility performance (MP), defined as mobility in real-life situations. This study examined the feasibility of a pendant sensor to continuously track MP during a 4-week period of chemotherapy. Methods: Patients on chemotherapy were recruited from a single center. Patients were asked to continuously wear a water-resistant pendant sensor (PAMSys, Biosensics, USA) for 4-weeks during the day and night. Patients completed psychosocial surveys (cognitive, depression, and fatigue) and a technology acceptance survey measured on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). Chart review was completed for demographics, medical history, and baseline ECOG PS. Using a validated algorithm, postures (lying and sitting postures: LSP) and walking parameters (cadence, longest walking bout, total steps per day) were extracted from the pendant. We also calculated percent change from baseline activity to the lowest activity level during the 4-week period. To determine clinically meaningful digital biomarkers, we compared these MP measures between two groups: ECOG 0 or ECOG ≥1. Results: Fifteen patients (median age 68), with either a solid (n = 14) or hematologic (n = 1) malignancy, stages II-IV, with ECOG 0 (n = 7) and ECOG ≥1 (n = 8) were evaluated. Baseline psychosocial parameters were not significantly different. ECOG ≥1 tend to have poorer baseline walking compared to ECOG 0 with the largest effect size observed for cadence (79.2 ± 10.0 vs 73.3±3.7, Cohen’s d effect size d = 0.78). The percentage of MP decline was higher in ECOG 0 compared to ECOG ≥1 (89.0±22.9% vs 79.9±34.5%). None of the observed trends reached statistical significance. Patients reported that the pendant was comfortable to wear (4.9±0.30) and did not interfere with activities (4.9±0.25). Conclusions: This study showed the feasibility of a pendant sensor to continuously monitor MP and its trajectory during chemotherapy. Results suggest continuous MP monitoring may provide objective information to enhance PS assessment. Larger studies are needed to confirm statistical significance of digital MP metrics and its potential effect on clinical decisions such as dose reduction, rehabilitation, and palliative care.

Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade.

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58–6.60, P = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 109/L versus low: ≤ 0.93 × 109/L, HR: 0.38, 95%CI: 0.23–0.62, P < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15–4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01–17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56–1.45, P = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41–1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.

Reflecting on survivorship outcomes to aid initial decision making in patients treated for IDH-mutated anaplastic glioma.

Patients with anaplastic glioma (AG) harboring an isocitrate dehydrogenase mutation have potential durable survival after intensity-modulated radiotherapy (IMRT) and chemotherapy. Understanding long-term functioning, and the factors that have an impact on later effects, is important for decision making. Consecutive patients with AG who received IMRT were reviewed with regard to 6 survivorship domains, including Eastern Cooperative Oncology Group (ECOG) performance status, Medical Research Council (MRC) neurological status, late toxicity, comorbidity, functional status (employment/driving), and psychosocial events. Assessments were performed at baseline before RT; at month +6; and at years +1, +3, and +5 after RT. The primary endpoints were ECOG at year +3 and employment at year +3. A total of 146 patients were included, with a median follow-up of 5.1years. The 6-year overall survival rate was 78.7% (95% CI, 71.1%-87.0%). Baseline ECOG performance status was 0 to 1 in 82.2% of patients but improved at year +1 (95.7%) and year +3 (97.2%). Employment rates at year +3 and year +5 were 70.1% and 76.5%, respectively, compared with 61.6% at baseline. Worse ECOG performance status at year +3 was related to the anaplastic astrocytoma subtype (P=.001), delayed RT (P=.081), multiple craniotomies performed before RT (P=.002), worse ECOG performance status before RT (P<.001), worse MRC neurological status before RT (P<.001), seizures (P=.038), neurocognitive disturbance (P<.001), and the presence of recurrent disease (P=.004). Absent or impaired employment at year +3 was found to be related to older age (P=.007), delayed timing of RT (P=.023), multiple craniotomies prior to RT (P=.005), worse ECOG performance status before RT (P<.001), worse MRC neurological status before RT (P<.001), and neurocognitive disturbance (P<.001). Patients with AG with an isocitrate dehydrogenase mutation have the potential for prolonged survival. Functional status appears to be good in patients who are free of disease progression at 3 to 5years after IMRT, with >95% of patients having high ECOG performance status and >75% being employed.

Interconversion of two commonly used performance tools: An analysis of 5844 paired assessments in 1501 lung cancer patients

AIMTo establish the Karnofsky performance status (KPS) categories which would facilitate the interconversion of the KPS scale to the Eastern Cooperative Oncology Group (ECOG) performance status (PS) scale.METHODSThis was a retrospective analysis of all patients attending the lung cancer clinic at a tertiary care center over a 5-year period (September 2009 to August 2014). All patients were assessed with both KPS and ECOG PS scales at each visit. Correlation between KPS and ECOG PS was assessed using Spearman’s correlation coefficient. KPS categories equivalent to ECOG PS scores were compared using hit rate and weighted kappa (κw).RESULTSA total of 1501 patients were assessed over the study period, providing 5844 paired KPS and ECOG PS assessments. The study cohort had a mean (standard deviation; SD) age of 58.4 (10.8) years, with the majority being current or ex-smokers (76.9%) and males (82.3%). Non-small cell lung cancer was the most common histological type (n = 1196, 79.7%) with the majority having advanced (stage IIIB/IV) disease (83.4%). Mean baseline KPS and ECOG PS scores were 77.6 (SD = 14.4) and 1.5 (SD = 1) respectively. The most frequent KPS score was 80 (29%), and the most frequent ECOG PS score was 1 (43%). The overall correlation between KPS and ECOG PS was good (Spearman r = -0.84, P < 0.0001) but ranged from -0.727 to -0.972 between visits. KPS categories derived from our cohort [10-40 (ECOG 4), 50-60 (ECOG 3), 70 (ECOG 2), 80-90 (ECOG 1), 100 (ECOG 0)] performed better [hit rate 78.1%, κw = 0.749 (0.736-0.762) P < 0.0001] than those suggested in the past literature.CONCLUSIONThe current study provides the largest set of paired KPS-ECOG assessments to date. We suggest that the KPS categories 10-40, 50-60, 70, 80-90, and 100 are equivalent to ECOG PS categories of 4, 3, 2, 1, and 0 respectively.

P2.01-77 Interconversion of Two Commonly Used Performance Tools: An Analysis of 5844 Paired Assessments in 1501 Lung Cancer Patients

Karnofsky Performance Status (KPS) scale and Eastern Cooperative Oncology Group (ECOG) scale are the most commonly used performance status (PS) tools worldwide. The current study aimed to assess correlation between KPS and ECOG PS in a large cohort from a lung cancer (LC) clinic database and to determine KPS categories which were most equivalent to ECOG PS scores. All patients attending LC clinic at a tertiary care centre over a 5-year period were assessed with both KPS and ECOG PS scales at each visit. Correlation between KPS and ECOG PS was assessed using Spearman’s correlation coefficient. Different KPS categories equivalent to ECOG PS were compared using hit rate and weighted kappa (κw). A total of 1501 patients were assessed over study period providing 5844 paired KPS and ECOG PS assessments. The cohort had a mean (standard deviation SD) age of 58.4 (10.8) years with majority being current/ex-smokers (76.9%) and males (82.3%). NSCLC was commonest histological type (n=1196, 79.7%) with majority having advanced (stages IIIB/IV) disease (83.4%). Mean baseline KPS and ECOG PS scores were 77.6 (SD=14.4) and 1.5 (SD=1) respectively. Overall correlation between KPS and ECOG PS was good [Spearman r = (-)0.84, P<0.0001] but ranged from -0.727 to -0.972 between visits. KPS categories derived from our cohort (10-40 [ECOG 4], 50-60 [ECOG 3], 70 [ECOG 2], 80-90 [ECOG 1], 100 [ECOG 0]) performed better (hit rate 78.1%, κw = 0.749 [0.736-0.762] P<0.0001) than those suggested in the past literature. The current study provides largest set of paired KPS-ECOG assessments till date. Although both PS tools had good correlation, the performance of the KPS categories previously suggested as being equivalent to ECOG PS categories was found to be highly variable. Cancer clinics should develop and validate their own population-specific KPS categories for interconversion of KPS to ECOG PS.

Radium-223 Safety, Efficacy, and Concurrent Use with Abiraterone or Enzalutamide: First U.S. Experience from an Expanded Access Program

In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use. This phase II, open-label, single-arm, multicenter U.S. EAP (NCT01516762) enrolled patients with symptomatic mCRPC, ≥2 bone metastases, and no lung, liver, or brain metastases. Patients received radium-223 55 kBq/kg intravenously every 4 weeks × 6. Primary outcomes were acute and long-term safety. Additional analyses were done by number of radium-223 injections, and prior or concomitant abiraterone or enzalutamide use. Of 252 patients, 184 received radium-223: 165/184 (90%) had Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 183 (99%) had prior systemic anticancer therapy. Treatment-related adverse events occurred in 93/184 (51%) patients during treatment and 11 (6%) during follow-up. Median overall survival was 17 months, with 134/184 (73%) patients censored because of short follow-up due to radium-223 approval. In post hoc analyses, patients with ≥3 prior anticancer medications, baseline ECOG performance status ≥2, and lower baseline hemoglobin were less likely to receive 5-6 radium-223 injections and unlikely to benefit from radium-223. Radium-223 was well tolerated regardless of concurrent or prior abiraterone or enzalutamide. Radium-223 was well tolerated, with no new safety concerns; safety was maintained with abiraterone or enzalutamide. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline characteristics and therapy sequence for greatest clinical value. In this phase II U.S. expanded access program, radium-223 was well tolerated, with a median overall survival of 17 months in metastatic castration-resistant prostate cancer patients. In post hoc analyses, radium-223 was safe regardless of concurrent abiraterone or enzalutamide, and median overall survival appeared longer when radium-223 was used earlier in patients with less prior treatment. Patients with more advanced disease were less likely to benefit from radium-223. Clinicians should consider baseline clinical characteristics and therapy sequence to provide the greatest clinical value to patients.

Patient Subgroup Analysis of Quality-of-Life Outcomes in Checkmate 205, a Phase 2 Study of Nivolumab in Patients with Classical Hodgkin Lymphoma

Introduction: Nivolumab is a fully human IgG4 immune checkpoint inhibitor targeting programmed death receptor-1 (PD-1). It has recently been approved by the FDA in the US for patients with classical Hodgkin lymphoma (cHL) who have failed autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplant brentuximab vedotin (cohort B of CheckMate 205). The objective response rates in cohort B of CheckMate 205 (NCT02181738) per independent radiologic review committee (IRRC) assessment was 66%, with median time to response of 2.1 months. Furthermore, mean EuroQol Five Dimensions (EQ-5D) visual analog scale (VAS) score increased over time during treatment with nivolumab, and European Organisation for Research and Treatment of Cancer Core Quality-of-Life questionnaire (EORTC QLQ-C30) data suggested an improvement from baseline (BL) across functional, symptom, and global health scores [Younes et al. Lancet Oncol 2016; Jul 20 (Epub ahead of print)]. The aim of the current analysis is to understand if quality-of-life (QoL) changes observed in the cohort of patients with cHL vary across patient subgroups.Methods: CheckMate 205 is a multi-cohort study evaluating the efficacy and safety of nivolumab 3 mg/kg by IV infusion every 2 wks in 3 cohorts of patients with cHL post-auto-HSCT. Patient-reportedgeneral health status was assessed using the 3-level version of the EQ-5D questionnaire, and cancer-specific QoL using the EORTC QLQ-C30. Questionnaires were administered to patients every 4 cycles (every 8 wks). All treated patients with BL and at least 1 post-BL assessment in cohort B were included in this analysis population. Scores were examined across prespecified patient subgroups, including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS) at BL, smoking status, B symptoms at BL, region (USA/Canada or Europe), and best overall response (BOR) per investigator assessment or IRRC at wks 9, 17, 25, and 33. Least squares (LS) means were used to describe post-BL score changes over time for the overall analysis population and subgroups. Minimally important differences were prespecified.Results: 72 patients (90%) from CheckMate 205, cohort B, completed BL and at least 1 post-BL EORTC QLQ-C30 or EQ-5D assessment. By wk 33, 58% of patients were included. The mean (SD) age was 38.9 (13.3) years. 34.7% of patients were female, 45.8% had BL ECOG PS 1, and 68.1% had stage IV disease at study entry. LS mean (standard error) score change from BL at wk 33 was 19.1 (3.1) for EQ-5D VAS and 7.6 (2.3) for the EORTC QLQ-C30 global health/QoL status scale. For the global health status subscale, all subgroup estimates were consistent with the overall changes from BL, except patients with absence of B symptoms who experienced significantly smaller changes at wk 17 only. For other EORTC subscales where statistically significant improvements in LS mean from BL were observed at each time point (fatigue, dyspnea, appetite loss, physical functioning, role functioning), although all subgroup estimates were in line with the overall change, there were some trends for non-smokers (vs smokers), ECOG PS 0 (vs 1), USA/Canada (vs Europe), and B symptoms at BL (vs none) toward better symptom improvement. Changes from BL across responders and non-responders were consistent with overall changes from BL.Conclusions: In this small cohort of patients with cHLwho had failed auto-HSCT and subsequent brentuximab vedotin, the improvement in QoL observed while on-treatment with nivolumab was mostly consistent across the subgroups investigated.Funding: Bristol-Myers Squibb (BMS). Medical writing: S Addison, Caudex, funded by BMS. DisclosuresEngert:Takeda, BMS: Consultancy, Honoraria, Research Funding. Taylor:Bristol-Myers Squibb: Consultancy. Bennett:Bristol-Myers Squibb: Consultancy. Hirji:Bristol-Myers Squibb: Employment. Cocks:Bristol-Myers Squibb: Consultancy. McDonald:Bristol-Myers Squibb: Consultancy. Mann:Bristol-Myers Squibb: Consultancy. Kato:Bristol-Myers Squibb: Employment. Cella:Alexion, Inc., Astellas, Biogen Idec, Celgene, Clovis Oncology, Inc., Daiichi Sankyo, Eli Lilly, Evidera, Inc., Exelixis, Fiborgen, Genetech, Helsinn Therapeutics, Inc., Immunogen, Ipsen Pharma, Janssen, Lexicon Pharmaceuticals, Inc., Merck, Novartis, Onc: Consultancy, Research Funding; Bristol-Meyers Squibb: Consultancy, Research Funding; Abbvie, Inc.: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bayer Pharmaceuticals, Inc.: Consultancy, Research Funding; Facit.org: Other: President.

Renal cell carcinoma in patients with end-stage renal disease is associated with more favourable histological features and prognosis

Objective. End-stage renal disease (ESRD) patients with acquired cystic kidney disease are at higher risk of developing renal cell carcinoma (RCC) than the general population. The aim of this study was to investigate the clinical and histopathological differences between ESRD patients and the general population with RCC. Materials and methods. Data were retrospectively collected from all nephrectomies performed for localized RCC from 2000 to 2010. Age at nephrectomy, gender, race, symptoms, baseline Eastern Cooperative Oncology Group (ECOG) performance status, Charlson Comorbidity Index score and histological data were extracted. Independent-samples t test and Mann–Whitney test were used for quantitative data, while chi-squared (two-sided) and Fisher’s exact tests were used for qualitative data. Results. This study included 627 patients: 73 with and 554 without ESRD. The majority of patients were Chinese. The male to female ratio of 2:1 was identical in both groups. Baseline ECOG performance status and Charlson Comorbidity score were higher in the ESRD group. RCC in ESRD patients was more frequently asymptomatic (56.2% vs 44.9%, p = 0.071), diagnosed earlier (53.6 ± 11.8 years vs 57.9 ± 12.2 years, p = 0.004) and of lower stage (p < 0.001). The ESRD cohort had a higher proportion of the papillary histological subtype (21.9% vs 9.7%, p < 0.001). Importantly, there was a trend towards more favourable outcomes in ESRD patients in terms of cancer-specific (p = 0.203) and relapse-free survival (p = 0.096). Conclusion. This study suggests that RCC in ESRD patients is associated with more favourable clinical and histological features and oncological outcome compared with that in patients with normal renal function.

Survival outcomes in the PRIME study for patients (pts) with RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC), by baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS).

3557^ Background: In PRIME, panitumumab (pmab) + FOLFOX4 improved overall survival (OS) for RAS WT mCRC pts vs FOLFOX4 alone (Douillard et al 2013). Prespecified subgroup analysis identified only E...

Multivariate and Subgroup Analyses of a Multinational Phase III Trial of Decitabine in Older Patients with Newly Diagnosed Acute Myeloid Leukemia

AbstractAbstract 3618 Introduction:A recent phase III trial compared efficacy and safety of decitabine with those of patient's treatment choice (TC) of supportive care or low-dose cytarabine in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics (Kantarjian et al. J Clin Oncol 2012;30:2760; NCT00260832). At the planned clinical cutoff date in 2009 (396 deaths), a nonsignificant trend toward increased median overall survival (OS) was seen with decitabine (7.7 months; 95% confidence interval [CI] 6.2, 9.2 months) vs TC (5.0 months; 95% CI: 4.3, 6.3 months); estimated hazard ratio (HR) 0.85 (P=.108). A 2010 post hoc analysis of mature data (446 deaths) from this study showed that the median OS had not changed but HR had improved (0.82; 95% CI 0.68, 0.99; nominal P=.037) and favored decitabine versus TC. At the 2009 cutoff, remission rates (complete response [CR] or CR with incomplete platelet recovery [CRp] were significantly improved with decitabine (17.8%) vs TC (7.8%; P=.001). Decitabine was generally well tolerated. A multivariate analysis was conducted using the mature (2010) data to identify potential predictors of OS in this older population with AML. Methods:Eligible patients were aged ≥65 years with newly diagnosed de novo or secondary AML (≥20% blasts), poor- or intermediate-risk cytogenetics, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2. Patients were randomized 1:1 to receive decitabine (20 mg/m2 intravenously once daily for 5 consecutive days every 4 weeks) or TC (supportive care or cytarabine 20 mg/m2 subcutaneously once daily for 10 days every 4 weeks), stratified by age, cytogenetic risk, and ECOG PS. A multivariate Cox proportional hazards model was used to investigate the effects of the following demographic and baseline characteristics on OS in addition to treatment effect: sex, age (<70, 70–<75, or ≥75 years), baseline cytogenetic risk (intermediate vs poor), AML type (de novo vs secondary), baseline ECOG PS (0/1 vs 2), geographic region (North America/Australia, Western Europe, Eastern Europe, Asia), baseline bone marrow blasts (>50% vs ≤50%), baseline platelet count (analyzed at each unit of 100 × 109/L) and baseline white blood cell (WBC) count (analyzed at each unit of 25 × 109/L). These potential prognostic factors were evaluated simultaneously, and values were not adjusted for multiple testing. Results:Of 485 randomized patients, 242 received decitabine and 243 received TC (cytarabine, n=215; supportive care, n=28). Baseline patient demographics and clinical characteristics were similar between groups and indicated a high-risk population: 71% of patients were aged ≥70 years, 35.3% had secondary AML, 36.0% had poor-risk cytogenetics, and 25.8% had ECOG PS 2 or higher; median baseline proportion of blasts in bone marrow was 46.0%. Patient characteristics that appeared to adversely affect OS at the 0.05 level included more advanced age, poorer baseline ECOG PS, poor cytogenetics, higher bone marrow blast count, low baseline platelet count, high WBC count, and geographic region (Western vs Eastern Europe) (Table). Conclusions:In older patients with AML, OS was associated with prognostic factors of age, ECOG PS, cytogenetic risk, baseline bone marrow blasts, baseline platelet counts, and baseline WBC in addition to responding differently to decitabine vs TC (supportive care or cytarabine). Treatment response is related both to patient and disease status in older patients with AML.TableMultivariate Analysis of Effects of Baseline Patient Demographics and Clinical Characteristics on Overall SurvivalVariableHR95% CIP valueTreatment: decitabine vs TC0.80(0.65, 0.98).030Age group70–74 vs <70 years1.31(1.00, 1.71).047≥75 vs <70 years1.56(1.20, 2.03).001Baseline cytogenetic risk: intermediate vs poor0.70(0.57, 0.87).001Baseline ECOG PS: 0 or 1 vs 20.77(0.61, 0.98).032Geographic region: Eastern vs Western Europe0.65(0.48, 0.88).005Baseline bone marrow blast: >50% vs ≤50%1.36(1.10, 1.67).005Baseline platelets (109/L)0.78a(0.66, 0.91).002Baseline WBC (109/L)1.26b(1.05, 1.51).015aHR <1 = lower risk associated with each additional 100 × 109/L in baseline platelet counts.bHR >1 = higher risk associated with each additional 25 × 109/L in baseline WBC counts. Disclosures:Mayer:Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: Decitabine is a nucleoside metabolic inhibitor indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups. Delaunay:Novartis, Genzyme: Consultancy. Jones:Eisai Inc: Employment. Berrak:Eisai Inc: Employment. Kantarjian:Eisai: Research Funding.

Utility of Inflammation-based Prognostic Scoring in Patients Given Systemic Chemotherapy First-line for Advanced Inoperable Bladder Cancer

Our intent was to investigate the impact of specific parameters-clinical status, performance status (Eastern Cooperative Oncology Group (ECOG)), C-reactive protein, serum albumin, and inflammation (Glasgow Prognostic Score)-on progression-free survival and overall survival in patients given systemic chemotherapy as the first-line treatment of advanced bladder cancer. A total of 67 patients treated for advanced bladder cancer in a 7-year period (2004-10) were reviewed. Prior to administration of first-line chemotherapy (gemcitabine plus cisplatin), baseline ECOG performance status, C-reactive protein, albumin, Glasgow Prognostic Score and clinical status were assessed. Patients with both elevated C-reactive protein (>1.0 mg/dl) and low albumin (<3.5 mg/dl) were assigned a Glasgow Prognostic Score of 2, while lesser scores were set when one (Glasgow Prognostic Score 1) or both levels (Glasgow Prognostic Score 0) were within the normal range. To evaluate relationships to progression-free survival and overall survival, univariate and multivariate analyses were conducted. By multivariate analysis, ECOG performance status (hazard ratio = 3.48, 95% confidence interval 1.87-6.45, P = 0.001) and hypoalbuminemia (hazard ratio = 2.04, 95% confidence interval 1.10-3.78, P = 0.023) were found to be factors independently associated with reduced progression-free survival. Factors independently associated with shortened overall survival were ECOG performance status (hazard ratio = 5.32, 95% confidence interval 2.22-12.71, P = 0.001) and Glasgow Prognostic Score 2 (hazard ratio = 7.00, 95% confidence interval 2.53-19.36, P = 0.001). These outcomes indicate that a systemic inflammatory response coupled with hypoalbuminemia (Glasgow Prognostic Score 2) correlates significantly with shortened overall survival and may thus be useful as a prognostic index in this setting.

Validity and utility of the University of Texas M. D. Anderson Symptom Inventory (MDASI) among prostate cancer patients: Data from E2Z02: Symptom Outcomes and Practice Patterns (SOAPP).

e15173 Background: Optimal treatment outcomes for patients (pts) with prostate cancer are dependent upon rigorous symptom assessment. The MDSAI, a patient-reported outcome measure of symptoms (sxs) and their impact validated in a sample of patients of diverse cancer types has the potential to inform symptom experience and guide treatment specific to prostate cancer pts. Methods: SOAPP, an Eastern Cooperative Oncology Group (ECOG) study, was conducted at academic and community medical oncology clinics and included pts with prostate cancer of all stages and phases of care. At baseline and 4 weeks, pts completed a measure of symptom severity and functional interference (MDASI). Symptom experiences and psychometric properties of the MDASI in prostate cancer pts (n = 320) were analyzed. Results: The 5 most prevalent moderate/severe sxs reported at baseline were fatigue (34%), disturbed sleep (25%), drowsiness (18%), pain (17%), and dry mouth (15%); moderate/severe nausea (5%) and vomiting (2%) were the least prevalent. At baseline ECOG performance status (PS) was ≥2 in 9% of pts. Pain, sadness, and difficulty remembering things occurred in 17%, 14%, and 13% respectively, and among pts whose PS worsened, severity of these sxs had the highest change scores at follow-up. Internal consistency and test-retest reliability of the MDASI were good, with Cronbach coefficient alphas ≥0.84 and intra-class correlations ≥0.78 for all subscales. Significantly higher scores and moderately large effects for the MDASI severity scale were reported by pts with poorer PS (2.2 vs 1.0, ES=.83) and tumor progression (2.4 vs 1.2, ES=.73) p&lt;.05. Results were similar for the interference scale, demonstrating MDASI known-group validity. Pts whose quality of life declined showed significantly greater increase in severity (1.1 vs .14, p&lt;.01) and interference (1.9 vs .28, p&lt;.004) from baseline to follow-up than pts whose quality of life was unchanged, demonstrating MDASI sensitivity to change. Conclusions: The MDASI is a valid, reliable, and sensitive symptom assessment method for descriptive and clinical studies, and patient care in medical oncology outpatients with prostate cancer.

Hazards for Pain Severity and Pain Interference with Daily Living, with Exploration of Brief Pain Inventory Cutpoints, Among Women with Metastatic Breast Cancer

Few longitudinal studies have assessed risk factors for pain outcomes in tumor-specific populations. Such studies are needed to improve clinical practice guidelines for cancer pain management over the course of treatment. Among patients with metastatic breast cancer, we assessed the impact of baseline clinical and demographic risk factors on patients reaching different pain severity and interference scores. We analyzed data originally collected in a clinical trial of two bisphosphonate therapies. Pain was measured by the Brief Pain Inventory (BPI) severity and interference with daily living 0–10 subscales. We fit univariate (per-cutpoint) and multivariate (cutpoints 3, 4, 5, 6, and 7 on the BPI) proportional hazards models to identify predictors of pain outcomes over 51 weeks among 1,124 women with metastatic breast cancer. Predictors included race, age, education, geographic region, performance status, chemotherapy versus hormonal therapy only, time from first bone metastasis to randomization, and previous skeletal-related event (SRE, e.g., fractures, spinal cord compression). Non-Caucasian women had greater hazards for reaching higher cutpoints (5 and above) on the severity scale than Caucasian women (hazard ratio [HR] for cutpoint 5 interaction term = 1.76; 95% confidence interval [CI] = 1.37–2.26). For the interference scale, these hazards were greater for those patients with restricted (versus active) baseline Eastern Cooperative Oncology Group (ECOG) performance status (HR for cutpoint 5 interaction term = 2.51; 95% CI = 2.01–3.13). In the multivariate severity model, other factors associated with higher pain severity were restricted baseline ECOG performance status, previous SRE, and not being employed full-time at baseline (HRs = 1.70, 1.23, and 1.33, respectively). Our findings that non-Caucasian race and restricted performance status were associated with greater pain hazards over time confirm previous cross-sectional findings that these characteristics are pain risk factors. Because we found that the most influential demographic and clinical baseline factors had predictive value for worsening outcomes as early as cutpoint 5, we recommend that pain management strategies use cutpoints informed by risk factors for worsening outcomes as cues for earlier intervention, thus delaying or preventing worst pain among women with metastatic disease who are at greatest risk.