Median Overall Survival Values Research Articles

A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer

sBackgroundTo evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes.MethodsAll 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m2) and weekly doses (250 mg/m2) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m2), leucovorin (200 mg/m2), and an IV bolus dose of 5-FU (400 mg/m2) followed by a continuous infusion of 5-FU (2400 mg/m2) for 46 h. The primary endpoint was time-to-progression (TTP).ResultsThe response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat analysis, median TTP was 4.6 months (95% confidential interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95% CI: 7.3-9.9 months). In univariate analyses, plasma vascular endothelial growth factor (VEGF) levels were correlated with clinical outcome. In patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values were 12 months and 5 months, respectively (P <0.0001). None of these patients exhibited KRAS, BRAF, or PIK3CA mutations.ConclusionsCombination therapy comprising cetuximab and mFOLFIRI was well tolerated and active as a second-line treatment for patients with metastatic gastric cancer. Patients with low baseline plasma VEGF levels were associated with better clinical outcomes.Trial registrationClinicalTrials.gov. NCT00699881. Registered 17 June 2008 (retrospectively registered)

2056A - Treatment compliance and outcome in geriatric patients with locally advanced non-small cell lung cancer: Experience from India

Objectives: To evaluate treatment compliance, toxicity and survival in geriatric patients (≥65 years) with locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Departmental archive was collected for the details of demographics, treatment and outcome in elderly patients with LA-NSCLC (2008 - 2013) (n = 96). Both progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Acute and late morbidity were scored using common terminology criteria for adverse events version 4, radiation therapy and oncology group late morbidity scoring system. Results: Overall treatment completion rate was 65%. The rates of acute grade ≥ 3 hematologic and non-hematologic toxicities were 20% and 17% respectively. Overall rate of late toxicity was 12.5%. The median PFS and OS values were 7.4 months and 10.54 months, respectively. Patients with multiple comorbidities, poor socio-economic background and serum albumin level (< 3.5g/dL) were observed to have poor survival. Survival was lower for non-compliant patients. Conclusions: Curative multi-modality therapy in elderly patients with LA-NSCLC is a challenging task. They are susceptible to poor compliance, treatment-associated toxicities and poor survival.

Treatment Compliance and Outcome in Geriatric Patients with Locally Advanced Non-Small Cell Lung Cancer: Experience from India

Objectives: To evaluate treatment compliance, toxicity and survival in geriatric patients (≥65 years) with locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Departmental archive was collected for the details of demographics, treatment and outcome in elderly patients with LA-NSCLC (2008 - 2013) (n = 96). Both progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Acute and late morbidity were scored using common terminology criteria for adverse events version 4, radiation therapy and oncology group late morbidity scoring system. Results: Overall treatment completion rate was 65%. The rates of acute grade ≥ 3 hematologic and non-hematologic toxicities were 20% and 17% respectively. Overall rate of late toxicity was 12.5%. The median PFS and OS values were 7.4 months and 10.54 months, respectively. Patients with multiple comorbidities, poor socio-economic background and serum albumin level (< 3.5g/dL) were observed to have poor survival. Survival was lower for non-compliant patients. Conclusions: Curative multi-modality therapy in elderly patients with LA-NSCLC is a challenging task. They are susceptible to poor compliance, treatment-associated toxicities and poor survival.

More sunlight exposure may improve the overall survival in patients with pancreas cancer

Abstract The protective effect of sun exposure on prognosis of cancer and cancer risk was previously reported in some studies except for melanoma and skin cancer. In presented study we aimed to compare the effect of sunlight exposure on prognosis of patients with pancreatic cancer (PC) in two regions with different sunlight exposure. Totally of 139 patients with PC from Akdeniz University from Antalya (n:103) and Kocatepe University (n:36) from Afyon were analyzed retrospectively. Antalya and Afyon state have different sunlight exposure. Two groups were compared in terms of overall survival (OS). The median OS values were 10,9 [95% CI: 7,8–14,0] and 6,9 [95% CI: 3,9–9,9] months for Antalya and Afyon groups, respectively and it was found a significant difference between groups for OS (p = 0.015). Also, the region and stage were an independent prognostic factor. In conclusion, the patients with PC had better OS in the region with more sunlight exposure.

Prognostic value of neutrophil-to-lymphocyte ratio in advanced oesophago-gastric cancer: exploratory analysis of the REAL-2 trial

The REAL-2 trial demonstrated that capecitabine and oxaliplatin were effective alternatives to fluorouracil and cisplatin, respectively, when used in triplet chemotherapy regimens for previously untreated oesophago-gastric cancer. The aim of the current analysis was to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in the REAL-2 cohort. A post hoc exploratory analysis was carried out on REAL-2 patients with the available absolute neutrophil count and absolute lymphocyte count. A high NLR was defined using a cut-off value of >3.0. The NLR was then correlated with clinical outcomes including overall survival (OS), progression-free survival (PFS) and objective response rate. Survival curves were generated using the Kaplan-Meier method and comparison between groups was carried out using Cox regression. Data were available in 908 of the 1002 REAL-2 participants. Of these, 516 (56.8%) were deemed to have a high NLR. In univariate analysis, high NLR was associated with a hazard ratio (HR) for OS of 1.73 (1.50-2.00), P < 0.001, compared with low NLR, equating to median OS values of 9.1 [95% confidence interval (CI) 8.0-9.6] and 12.7 months (95% CI 10.8-14.4), respectively. The NLR remained highly significant for OS (P < 0.001) in a multivariate model including performance status, age, disease extent, presence of liver metastases and presence of peritoneal metastases. For PFS, high NLR was associated with an HR of 1.63 (1.41-1.87), P < 0.001, compared with low NLR in univariate analysis. No significant interaction was found between NLR status and treatment arm, 13% of all patients with low NLR achieving survival beyond 24 months compared with only 6% of patients with high NLR (P < 0.001). Our results confirm that high NLR status had a significant negative prognostic effect in the REAL-2 trial population. Based on the multivariate analysis, this effect was independent of other known prognostic factors.

Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis.

It is well known that peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is associated with a poor prognosis. However, data on the prognostic significance of modern chemotherapy containing bevacizumab, cetuximab or panitumumab are not available. This retrospective review concerned 526 patients with metastatic CRC who were classified into two groups according to the presence or absence of PC, and were treated with systemic chemotherapy, with or without bevacizumab or anti-EGFR antibodies. The genetic background, in particular KRAS, BRAF, and PIK3CA gene mutations, and overall survival (OS) were compared between the two groups. The median OS values were 23.3 and 29.1 months for PC and non-PC patients, respectively (hazard ratio [HR]=1.20; p=0.17). Among all patients, tumor location, number of metastatic sites and BRAF mutation status were significant prognostic factors, whereas the presence of PC was not. In the PC group, chemotherapy with bevacizumab resulted in a significantly longer OS than forchemotherapy without bevacizumab (HR=0.38, p<0.01), but this was not the case in the non-PC group (HR=0.80, p=0.10). Furthermore, the incidence of the BRAF V600E mutation was significantly higher in PC than in non-PC patients (27.7% versus 7.3%, p<0.01). BRAF mutations displayed a strong correlation with shorter OS in non-PC (HR=2.26), but not PC patients (HR=1.04). Systemic chemotherapy, especially when combined with bevacizumab, improved survival in patients with PC from CRC as well as non-PC patients. While BRAF mutation demonstrated a high frequency in PC patients, but it was not associated with prognosis.

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

BackgroundWe investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC). MethodsWe included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS. ResultsGlobal health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively). ConclusionThis study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.

Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy.

BackgroundSingle-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms − FAS −670 A>G, FAS ligand −844 T>C, survivin −31 G>C, and survivin 9386 C>T – with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy.Materials and methodsPolymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique.ResultsPatients with the CC genotype of FAS −670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS −670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively).ConclusionThe functional FAS −670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

Randomized Phase II Open-Label Study of mFOLFOX6 in Combination With Linifanib or Bevacizumab for Metastatic Colorectal Cancer

BackgroundAlthough CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC. Patients and MethodsOne hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety. ResultsNo statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab. ConclusionCombining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.

Translational assessment of mitochondrial dysfunction of pancreatic cancer from in vitro gene microarray and animal efficacy studies, to early clinical studies, via the novel tumor-specific anti-mitochondrial agent, CPI-613.

Via genetic alterations, malignant transformation and proliferation are associated with extensive alterations of mitochondrial energy metabolism of tumor cells. Thus, inhibition of the altered form of mitochondrial energy metabolism of tumor cells may be an effective therapy for cancers. This study performed translational assessment of mitochondrial dysfunction of pancreatic cancer from in vitro gene microarray and animal efficacy studies, to early clinical studies, via the novel tumor-specific anti-mitochondrial agent, CPI-613. The gene profiles of BxPC-3 human pancreatic tumor cells and non-transformed NIH-3T3 mouse fibroblast cells (negative control), after CPI-613 or sham treatment, were assessed and compared using microarray technique. The anti-cancer efficacies of CPI-613 and Gemcitabine were assessed and compared in mice with xenograft from inoculation of BxPC-3 human pancreatic tumor cells, based on the degree of tumor growth inhibition and prolongation of survival when compared to vehicle treatment. The anti-cancer activities, according to overall survival (OS), of CPI-613 alone and in combination with Gemcitabine were assessed in patients with Stage IV pancreatic cancer. Microarray studies indicated that CPI-613 down-regulated the expression of Cyclin D3, E1, E2, F, A2, B1 and CDK2 genes of BxPC-3 pancreatic cancer cells but not non-transformed NIH-3T3 mouse fibroblast cells (negative control). In mice with pancreatic carcinoma xenografts, four weekly intraperitoneal injections of either CPI-613 (25 mg/kg/administration) or Gemcitabine (50 mg/kg/administration) inhibited tumor growth and prolonged survival when compared to vehicle treatment. The degree of tumor growth inhibition was ~2×, and prolongation of survival was ~4×, greater with CPI-613 treatment than with Gemcitabine treatment. In patients with Stage IV advanced pancreatic cancer, CPI-613 at 420-1,300 mg/m(2), given twice weekly for three weeks followed by a week of rest (i.e., 3-week-on-1-week-off) as monotherapy, provided median OS of 15 months in three patients. CPI-613 at 150-320 mg/m(2) given twice weekly on the 3-week-on-1-week-off dosing schedule, coinciding with Gemcitabine (1,000 mg/m(2)) given once weekly on the 3-week-on-1-week-off dosing schedule, provided median OS of 17.8 months in four patients. These median OS values from CPI-613 monotherapy and CPI-613 + Gemcitabine treatment tend to be longer than those in patients treated with Abraxane + Gemcitabine combination or FOLFININOX (median OS ~12 months). The dysfunctional mitochondria of pancreatic cancer cells was translationable from in vitro gene alteration and animal tumor model studies to patients with advanced Stage IV pancreatic cancer, as reflected by the anti-cancer activities of the tumor-specific anti-mitochondrial agent, CPI-613, in these studies.

The Effect of Haematological Parameters on Overall Survival in Advanced Stage Non Small Cell Lung Cancer.

In this study, we aimed to evaluate the prognostic value of pretreatment blood count values, particularly WBC counts, in patients with advanced non-small cell lung cancer (NSCLC). The records of 186 patients with advanced stage (stage IIIB and IV) NSCLC were assessed retrospectively. Patients were divided into 3 subgroups according to WBC levels; ≤10000 /mm3 as Group 1, >10000 and ≤15000/mm3 as Group 2 and >15000/mm3 as Group 3. Patient and tumor characteristics as well as outcomes in terms of overall survival (OS) were evaluated. Median OS was 13.3 months in the whole population, 25.7 months in stage IIIB and 8.9 months in stage IV patients. According to the pretreatment leukocyte values, median OS was 17.9 months in Group 1, 11.2 months in Group 2 and 8.4 months in Group 3 (p= 0.003). Median OS values in WBC groups according to stages IIIB and IV were significantly different (p< 0.001). In multivariate analyses, ECOG-PS 2 or 3, stage IV disease, anemia and high WBC levels were associated with poorer OS. In this study, higher pretreatment WBC levels were associated with poorer OS in patients with advanced stage NSCLC. Pretreatment WBC counts may represent a simple prognostic factor and may aid in tailoring treatment in patients with advanced NSCLC.

Updated Prognostic Model for Predicting Overall Survival in First-Line Chemotherapy for Patients With Metastatic Castration-Resistant Prostate Cancer

Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy. Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC). The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively. An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis.

An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM) in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores) and breast cancer subtypes. Independent prognostic factors for overall survival (OS) were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respectively (p < 0.0001) and according to genetic subtypes, they were 5, 14.2, 16.5 and 17.1 months for basal-like, luminal A and B and HER, respectively (p = 0.04). Using multivariate analysis, we established a new grading system using the six factors that were identified as indicators of longer survival: age under 60 (p = 0.001), high KPS (p = 0.007), primary tumor control (p = 0.05), low number of extracranial metastases and BM (p = 0.01 and 0.0002, respectively) and triple negative subtype (p = 0.002). Three groups with significantly different median survival times were identified: 4.1, 9.5 and 26.3 months, respectively (p < 0.0001). Our new grading system shows that prognostic indexes could be improved by using more levels of classification and confirms the strength of biological prognostic factors.

Clinical Study of Thalidomide Combined with Dexamethasone for the Treatment of Elderly Patients with Newly Diagnosed Multiple Myeloma

To investigate the relationship between the efficacy and safety of different doses of thalidomide (Thal) plus dexamethasone (Dex) as the initial therapy in elderly patients with newly diagnosed multiple myeloma (MM). Clinical data of 28 elderly patients with newly diagnosed MM who underwent the TD regimen as the initial therapy were analyzed retrospectively. The patients were divided into two groups according to the maximal sustained dose of Thal: lower dose (group A) and higher dose (group B). The overall response rate (ORR), progression free survival (PFS), overall survival (OS), and adverse events (AES) were compared between the two groups. A total of 28 patients were followed up with a median of 18 months. The ORR was 60.1%. The median response time and PFS were 2.0 and 17.0 months, respectively. The mean sustained dose of Thal in group B was significantly higher than group A (292.9 mg v 180.4 mg, P=0.01). There was no significantly difference in ORR (57.1% v 64.3%, P=1.00) and PFS (9.63months v 17.66 months, P=0.73) between groups A and B. During the follow up, only five patients died (<40%) and, therefore, median OS values were not available. It is estimated, however, that the mean survival time in the two groups was 35.6 and 33.4 months (P>0.05), respectively. All of the patients tolerated the treatment well. The incidence of AES in patients with a grading above 3 in group B was significantly higher than in group A (P=0.033). The TD regimen results in a high response rate and manageable AES as the initial therapy in elderly patients with MM. TD should be considered as the front line regimen for the treatment of elderly patients with MM in areas with financial constraints. The clinical response can be achieved at a low dose Thal with minimal toxicity.

696P - A Multi-Center Phase II Study and Predictive Biomarker Analysis of Combined Cetuximab and Modified Folfiri as Second-Line Treatment in Patients with Metastatic Gastric Cancer

ABSTRACT Background This study was conducted to explore potential biomarkers for predicting clinical outcome of cetuximab in combination with modified FOLFIRI (mFOLFIRI) and to analyze safety of this regimen as a second-line treatment in metastatic gastric cancer patients. Methods A total of 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m2) and weekly doses (250 mg/m2) thereafter. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m2), leucovorin (200 mg/m2), and an IV bolus dose of 5-FU (400 mg/m2) followed by a continuous infusion of 5-FU (2400 mg/m2) for 46 hours. The primary endpoint was time-to-progression (TTP). Findings The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat (ITT) analysis, median TTP was 4.6 months (95% confidential interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95% CI: 7.3-9.9 months). It was demonstrated that plasma vascular endothelial growth factor (VEGF) levels could be a predictive factor for the treatment prognosis. In patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values were 12 months and 5 months, respectively (P Interpretation Low baseline plasma VEGF levels were identified as a potential predictive biomarker of prognosis. Combination therapy comprising cetuximab and mFOLFIRI was well tolerated, which would be potentially used as a second-line treatment for patients with advanced gastric cancer. Funding This study was supported by Fudan University Shanghai Cancer Center; Merck KGaA Darmstadt, Germany, and National “Eleventh Five-year plan” new drug discovery major projects of P. R. China. Disclosure All authors have declared no conflicts of interest.

Cost-effectiveness evaluation of abiraterone in the treatment of patients with castration-resistant prostate cancer who previously received docetaxel.

e15107 Background: Treatment with abiraterone improves overall survival (OS), time to prostate-specific antigen progression and radiologic progression-free survival when added to prednisone and best supportive care in patients with advanced castrate-resistant prostate cancer (CRPC) who previously received docetaxel. Little is known about its cost-effectiveness in the United States. Methods: In order to raise awareness of pharmacoeconomics concepts and inform policy-makers in the US, this study aimed to assess the cost-effectiveness of abiraterone in the treatment of advanced CRPC patients, from a payer perspective. We created a decision-analytical model using clinical data from the pivotal phase III trial: COU-AA-301. Health utilities were derived from the available literature. Costs for drug acquisition, physician visits and laboratory tests were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2011 US dollars. Life-years saved (LY), Quality-adjusted life years (QALY) and Incremental Cost Effectiveness Ratio (ICER) were calculated using updated survival data presented at the 2011 ASCO meeting. Other main scenarios used the original median survival data published in the New England Journal of Medicine article and adjusted median OS to represent an overall survival hazard ratio of .66. Sensitivity analyses were performed using the confidence intervals for median OS in the pivotal study as well as by halving or doubling all other model inputs. No discounting was used due to the short time-horizon. Results: Abiraterone added 0.38 LY and 0.30 QALY with an incremental cost of $39,320 and therefore a cost of $102,600/LY and an ICER of $129,000/QALY. The main drivers of the model were drug acquisition cost, median OS, and health utility values. The results of the model were robust in different scenarios and sensitivity analyses. Conclusions: Using commonly accepted willingness-to-pay thresholds, such as those suggested by the World Health Organization, treatment of patients with advanced CRPC patients with abiraterone is likely to be cost-effective in the US.

Tumor burden as an independent prognostic factor in metastatic renal cell carcinoma (mRCC).

397 Background: During the last ten years, several classifications have been used to assess the prognosis in mRCC. In none of them, tumor burden (TB) has been considered. This study investigates the prognostic role of baseline TB in terms of progression free survival (PFS) and overall survival (OS), in patients with mRCC. Methods: All patients with clear cell mRCC enrolled in our center, in 2 second-line trials, post cytokine, with sunitinib and sorafenib or placebo (Escudier JCO 2009, Escudier NEJM 2007), were selected for this analysis. TB was defined as the sum of the longest unidimensional diameter of each target lesions assessed using RECIST criteria. PFS and OS were estimated using Kaplan-Meier method and compared using the log-rank test. Association between TB and PFS or OS was evaluated using the Cox proportional hazards model. Multivariable analyses were adjusted for modified MSKCC risk class and treatment. Non-parametric Spearman rank test (rs) was used to assess the correlations between TB and MSKCC risk groups or ECOG Performance Status (PS). Results: Final population included 124 patients: 66% received sorafenib or sunitinib and 34% received placebo; median follow up was 80.1 months (IQR: 68.8 – 88.0). Baseline TB was divided into 3 tertiles (1.3 - 9.4 cm; 9.5 - 19.0 cm; 19.1 - 47.3 cm). TB was related to PFS and OS and, when adjusting for modified MSKCC risk class and treatment, these associations remained significant: each 1 cm increase in TB increased the progression risk by 5% (HR: 1.05; 95%CI, 1.02 – 1.07; p &lt; 0.0001) and the death risk by 5% (HR: 1.05; 95%CI, 1.03 – 1.08; p &lt; 0.0001). OS decreased with TB: the median tertiles OS values were: 42.1 months (95%CI: 24.0 – 60.2), 20.1 months (95%CI: 14.5 – 25.7), and 11.2 months (95%CI: 4.8 – 17.6), respectively (p &lt; 0.0001, figure 2). The TB was positively related to ECOG PS (rs = 0.357; p &lt; 0.0001) and to MSKCC risk score (rs = 0.478; p &lt; 0.0001). Patients with higher TB had shorter PFS, shorter OS, poorer MSKCC score and increased ECOG PS. Conclusions: TB is easy to calculate with standard CT and significantly relates to OS and PFS in patients with mRCC. We report for the first time the independent prognostic role of baseline TB in mRCC.

Kinetic analysis of breast tumor decay and growth following ixabepilone plus capecitabine (IXA + CAP) versus capecitabine alone (CAP) to discern whether the superiority of the combination is a result of slower growth, enhanced tumor cell kill, or both.

1096 Background: Utilizing a new method that analyzes tumor measurements obtained while a patient receives chemotherapy, we have previously shown for prostate and renal tumors that the growth rate constant of a tumor correlates with survival (Stein et al, Oncologist, 13:1046 and 1055; 2008). We have now applied this same approach to data collected in a clinical trial of IXA + CAP versus CAP alone in patients with metastatic breast cancer (MBC). Methods: Using CT tumor measurements obtained while patients were treated we determined the rate of tumor decay (d) and growth (g) reliably even before the nadir is reached. Results: (i) In patients treated with CAP, overall survival (OS) was strongly correlated (R > 0.59, p < 0.001) with the rate of tumor growth (log g) but less strongly (R > 0.21, p > 0.028) with the rate of decay (log d). The median growth rate constant for these tumors was 0.00288 days-1. For IXA + CAP, correlations of OS with both log g (R > 0.57, p < 0.001) and log d (R > 0.27, p > 0.0003) were similar to those for CAP. The median g value for IXA + CAP at 0.00191 days-1 was significantly lower than for CAP (p < 0.001), while median d values were similar (0.00840 days-1 for CAP; 0.00863 days-1 for CAP + IXA, p > 0.400 NS). (ii) For neither arm did g or d correlate with initial tumor burden. (iii) The median OS for the patients in this analysis treated with IXA + CAP (475 d) was significantly longer (p > 0.02) than that for the group treated with CAP (392 d) - in strict proportion to the reduction in the tumor growth rate constant. (iv) These median OS values were, however, shorter than those predicted from the on-study g and d parameters, suggesting continuation of drug treatment might have resulted in an increase in OS. Conclusions: We present a quantitative kinetic analysis of the response of breast tumors to chemotherapy as a robust and rapid method to assess results of clinical trials. Reduction of the on- study tumor growth rate with the addition of IXA was responsible for the enhanced OS seen with the combination. Continuation of treatment with IXA might conceivably have extended patient survival even further. No significant financial relationships to disclose.