Comparison of cetuximab (Cmab) with panitumumab (Pmab) monotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 663-663
Author(s):  
Akira Ueda ◽  
Satoshi Yuki ◽  
Takahide Sasaki ◽  
Yoshimitsu Kobayashi ◽  
Ayumu Hosokawa ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Wild Type ◽  
Significant Difference

663 Background: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) such as Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Monotherapy with Cmab or Pmab demonstrated the effectiveness in salvage-line, and the direct comparison was reported in ESMO 2013 (ASPECCT trial). Methods: Data of 31 pts with mCRC treated by monotherapy with Cmab (HGCSG0901) and 51 pts by monotherapy with Pmab (HGCSG1002) registered from 27 institutions in Japan. Comparison of Cmab with Pmab was retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab vs. Pmab); male/female 20/11 vs. 27/24, median age (range) 65(44-76) vs. 64(44-81), PS 0-1/2-3 21/10 vs. 46/5, number of metastatic organs 1-2/3- 22/9 vs. 25/16. Skin toxicity was common adverse events and was generally similar in two groups. MST was 8.4 months in the Cmab and 8.1 months in the Pmab (p = 0.32). PFS was 3.8 months in the Cmab, as compared with 3.1 months in the Pmab (p = 0.60); the corresponding response rate was 19.4% and 13.7% (p = 0.54). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.939, 95% CI 0.783-1.128, p = 0.503), nor PFS (HR 0.972, 95% CI 0.823-1.148, p = 0.735). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab monotherapy in the salvage-line treatment of pts with mCRC.

Comparison of adding cetuximab (Cmab) or panitumumab (Pmab) to irinotecan (IRI)-based chemotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 598-598
Author(s):  
Koshi Fujikawa ◽  
Satoshi Yuki ◽  
Takahide Sasaki ◽  
Yasuo Takahashi ◽  
Ichiro Iwanaga ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Wild Type ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Significant Difference

598 Background: Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Although IRI-based chemotherapy combined with Cmab or Pmab has demonstrated the effectiveness in salvage-line, there has been no reported trials comparing these antibodies directly. Methods: Data of 96 pts with mCRC treated by Cmab plus IRI-based chemotherapy (Cmab/IRI) from HGCSG 0901 and 27 pts treated by Pmab plus IRI-based chemotherapy (Pmab/IRI) from HGCSG1002 were retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/ irinotecan/ oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab/IRI vs. Pmab/IRI); male/female 58/38 vs. 16/11, median age (range) 63(38-80) vs. 64(49-81), PS 0/1/2 52/35/9 vs. 21/6/0, number of metastatic organs 1/2/3- 29/37/30 vs. 6/12/7, prior bevacizumab administration 62.5% vs. 92.6% (p = 0.002). MST was 9.9 months in the Cmab/IRI and 14.9 months in the Pmab/IRI (p = 0.196). PFS was 4.8 months in the Cmab/IRI, as compared with 5.4 months in the Pmab (p = 0.083); the corresponding RR was 25.0 % and 18.5% (p = 0.611). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.908, 95% CI 0.513-1.610, p = 0.742), nor PFS (HR 0.732, 95% CI 0.447-1.199, p = 0.732). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab with IRI-based chemotherapy in the salvage-line treatment of pts with mCRC.

Analysis of the GERCOR index in KRAS Exon2 WT patients with mCRC treated with salvage-line cetuximab-based chemotherapy: HGCSG0901.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 781-781
Author(s):  
Ayumu Hosokawa ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kazuteru Hatanaka ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Significant Difference

781 Background: The GERCOR index (GI) based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, in the salvage setting, the validity of the GI has not been reported in patients treated with cetuximab (Cmab)-based chemotherapy. Methods: 269 patients with mCRC treated with Cmab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS Exon2 wild type patients who were refractory to or intolerant of 5-FU / irinotecan/ oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 132 patients. Median OS and PFS were 9.8 and 4.3 months. The distribution and median OS / PFS for GI were as follows: low risk (L)(n = 28; 17.9/3.8 months), intermediate risk (I)(n = 52; 12.2/5.0 months), and high risk (H)(n = 52; 7.5/4.1 months). For OS, there was significant difference between L and H (p < 0.001) and between I and H (p < 0.001), but not between L and I (p = 0.076). For PFS, there was significant difference between I and H (p = 0.017), but not between L and I (p = 0.407), and between L and H (p = 0.222). In the Cox multivariate analysis, GI showed an independent prognostic impact (L vs. I ; HR 2.195, p=0.003 / L vs. H ; HR 4.028, p<0.001), but not predictive impact (L vs. I ; HR 0.987, p=0.958 / L vs. H ; HR 1.314, p=0.268). Conclusions: In this analysis, GI might be a prognostic factor in salvage treatment with Cmab-based chemotherapy.

Effect of chest-compression-only bystander cardiopulmonary resuscitation on the likelihood of initial shockable rhythm after out-of-hospital cardiac arrest: a propensity matching analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Funada ◽  
Y Goto ◽  
T Maeda ◽  
H Okada ◽  
M Takamura
Keyword(s):  
Cardiac Arrest ◽  
Chest Compression ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Shockable Rhythm ◽  
Significant Difference ◽  
Bystander Cardiopulmonary Resuscitation ◽  
Bystander Cpr

Abstract Background/Introduction Shockable rhythm after cardiac arrest is highly expected after early initiation of bystander cardiopulmonary resuscitation (CPR) owing to increased coronary perfusion. However, the relationship between bystander CPR and initial shockable rhythm in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. We hypothesized that chest-compression-only CPR (CC-CPR) before emergency medical service (EMS) arrival has an equivalent effect on the likelihood of initial shockable rhythm to the standard CPR (chest compression plus rescue breathing [S-CPR]). Purpose We aimed to examine the rate of initial shockable rhythm and 1-month outcomes in patients who received bystander CPR after OHCA. Methods The study included 59,688 patients (age, ≥18 years) who received bystander CPR after an OHCA with a presumed cardiac origin witnessed by a layperson in a prospectively recorded Japanese nationwide Utstein-style database from 2013 to 2017. Patients who received public-access defibrillation before arrival of the EMS personnel were excluded. The patients were divided into CC-CPR (n=51,520) and S-CPR (n=8168) groups according to the type of bystander CPR received. The primary end point was initial shockable rhythm recorded by the EMS personnel just after arrival at the site. The secondary end point was the 1-month outcomes (survival and neurologically intact survival) after OHCA. In the statistical analyses, a Cox proportional hazards model was applied to reflect the different bystander CPR durations before/after propensity score (PS) matching. Results The crude rate of the initial shockable rhythm in the CC-CPR group (21.3%, 10,946/51,520) was significantly higher than that in the S-CPR group (17.6%, 1441/8168, p&lt;0.0001) before PS matching. However, no significant difference in the rate of initial shockable rhythm was found between the 2 groups after PS matching (18.3% [1493/8168] vs 17.6% [1441/8168], p=0.30). In the Cox proportional hazards model, CC-CPR was more negatively associated with the initial shockable rhythm before PS matching (unadjusted hazards ratio [HR], 0.97; 95% confidence interval [CI], 0.94–0.99; p=0.012; adjusted HR, 0.92; 95% CI, 0.89–0.94; p&lt;0.0001) than S-CPR. After PS matching, however, no significant difference was found between the 2 groups (adjusted HR of CC-CPR compared with S-CPR, 0.97; 95% CI, 0.94–1.00; p=0.09). No significant differences were found between C-CPR and S-CPR in the 1-month outcomes after PS matching as follows, respectively: survival, 8.5% and 10.1%; adjusted odds ratio, 0.89; 95% CI, 0.79–1.00; p=0.07; cerebral performance category 1 or 2, 5.5% and 6.9%; adjusted odds, 0.86; 95% CI, 0.74–1.00; p=0.052. Conclusions Compared with S-CPR, the CC-CPR before EMS arrival had an equivalent multivariable-adjusted association with the likelihood of initial shockable rhythm in the patients with OHCA due to presumed cardiac causes that was witnessed by a layperson. Funding Acknowledgement Type of funding source: None

scholarly journals The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma

2017 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Reza Mehrazin ◽  
Essel Dulaimi ◽  
Robert G. Uzzo ◽  
Karthik Devarjan ◽  
Jianming Pei ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cytogenetic Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Renal Tumors ◽  
Rank Test

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jian-jun Li ◽  
Yexuan Cao ◽  
Hui-Wen Zhang ◽  
Jing-Lu Jin ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Glucose Metabolism ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

scholarly journals Para-Aortic Nodal Radiation in the Definitive Management of Node-Positive Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jason C. Sanders ◽  
Donald A. Muller ◽  
Sunil W. Dutta ◽  
Taylor J. Corriher ◽  
Kari L. Ring ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Chi Square ◽  
Node Positive ◽  
Significant Difference ◽  
Grade 3 ◽  
Severe Grade

ObjectivesTo investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer.MethodsPatients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test.Results96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p&gt;0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11).ConclusionsElective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.

scholarly journals Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study

2021 ◽  
Author(s):  
Miguel I. Paredes ◽  
Stephanie Lunn ◽  
Michael Famulare ◽  
Lauren A. Frisbie ◽  
Ian Painter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Sentinel Surveillance ◽  
Cox Proportional Hazards Model ◽  
Ancestral Lineage ◽  
Significant Difference

Background: The COVID–19 pandemic is now dominated by variant lineages; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the risk of hospitalization following infection with nine variants of concern or interest (VOC/VOI). Methods: Our study includes individuals with positive SARS–CoV–2 RT PCR in the Washington Disease Reporting System and with available viral genome data, from December 1, 2020 to July 30, 2021. The main analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for the risk of hospitalization following infection with a VOC/VOI, adjusting for age, sex, and vaccination status. Findings: Of the 27,814 cases, 23,170 (83.3%) were sequenced through sentinel surveillance, of which 726 (3.1%) were hospitalized due to COVID–19. Higher hospitalization risk was found for infections with Gamma (HR 3.17, 95% CI 2.15–4.67), Beta (HR: 2.97, 95% CI 1.65–5.35), Delta (HR: 2.30, 95% CI 1.69–3.15), and Alpha (HR 1.59, 95% CI 1.26–1.99) compared to infections with an ancestral lineage. Following VOC infection, unvaccinated patients show a similar higher hospitalization risk, while vaccinated patients show no significant difference in risk, both when compared to unvaccinated, ancestral lineage cases. Interpretation: Infection with a VOC results in a higher hospitalization risk, with an active vaccination attenuating that risk. Our findings support promoting hospital preparedness, vaccination, and robust genomic surveillance.

scholarly journals Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses

2021 ◽  
Vol 7 (1) ◽  
pp. 00543-2020
Author(s):  
Balázs Csoma ◽  
András Bikov ◽  
Ferenc Tóth ◽  
György Losonczy ◽  
Veronika Müller ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Full Blood Count ◽  
Rank Test ◽  
Severe Exacerbation ◽  
Increased Risk ◽  
Exacerbation Of Copd

Background and objectiveThe relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.MethodsPatients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.ResultsWe did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL−1, n=51, median (interquartile range): 21 (10–36) weeks) and non-eosinophilic groups (n=101, 17 (9–36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL−1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.ConclusionsOur data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.

Treatment of metastatic disease with immune checkpoint inhibitors nivolumab and pembrolizumab: Effect of performance status on clinical outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18689-e18689
Author(s):  
Leah Wells ◽  
Michael Cerniglia ◽  
Audrey C. Jost ◽  
Gregory Joseph Britt
Keyword(s):  
Disease Control ◽  
Proportional Hazards Model ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Time To Death ◽  
Significant Difference ◽  
Line Of Therapy

e18689 Background: While guidelines exist for appropriate use of chemotherapy in the metastatic setting based on performance status, such recommendations are less readily available for immune checkpoint inhibitors (ICIs). We sought to determine if there is a relationship between Eastern Cooperative Oncology Group (ECOG) performance status and outcomes on immunotherapy in patients treated for metastatic disease at our community-based oncology practice. Methods: 253 patients were identified as receiving nivolumab or pembrolizumab for stage IV malignancy at Cancer Centers of Colorado-SCL Health, between June 2018 and November 2020. Patients initiated on therapy after May 2020 were excluded from analysis, due to insufficient (less than 6 months) follow-up time. The remaining 183 patients were included in a retrospective cohort study comparing patients with ECOG 0, ECOG 1, and ECOG 2-4. Sex, age, type of cancer, and line of therapy were collected. Time on therapy was also calculated. Best response to therapy was determined (disease control or progressive disease). These baseline factors and outcomes were compared using ANOVA for numeric variables and chi-square tests of association for categorical variables. Time from initiation of ICI to death or hospice was also investigated and compared using a log-rank test. In addition, a multivariate Cox proportional hazards model was developed for the outcome, time to death/hospice, versus the predictors ECOG status, age, gender, and line of therapy. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated. Results: Of the 183 patients included in analysis, 31.7% had an ECOG of 0, 48.6% an ECOG of 1, and 19.7% an ECOG of 2-4. Non-small cell lung cancer and melanoma represented the majority of patients in each group. Gender and line of therapy did not differ between groups. There was a significant difference in age (p = 0.02) with mean age 62, 66, and 70 in ECOG 0,1, and 2-4, respectively. 54.6% of patients remained on therapy for at least 6 months (182 days), and there was no significant difference between groups in ability to complete 6 months of therapy (p = 0.32). For ECOG 0, 1, and 2-4, disease control was achieved in 67.2%, 59.6 %, and 41.7%, respectively (p = 0.048). Analysis of time to death/hospice with a log rank test and Kaplan Meier plot showed a significant difference between groups (p < 0.001). A multivariate Cox proportional hazards model revealed that patients with ECOG 0 had significantly longer time to death/hospice compared to patients in both other groups, after controlling for age, gender, and line of therapy (ECOG 1 vs. 0: HR 2.5, CI 1.27-4.9; ECOG 2-4 vs. 0: HR 2.83, CI 1.31-6.13). Conclusions: In this single institution retrospective study of patients receiving nivolumab or pembrolizumab for metastatic cancer, ECOG 0 was associated with disease control and increased time before death or transition to hospice.

Tumor IGF-1 expression as a predictive biomarker for IGF1R-directed therapy in advanced pancreatic cancer (APC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4054-4054 ◽  
Author(s):  
Milind M. Javle ◽  
Rachna T. Shroff ◽  
Gauri R. Varadhachary ◽  
Robert A. Wolff ◽  
David R. Fogelman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Primary Study ◽  
Study Objective ◽  
Log Rank Test ◽  
Hazards Model

4054 Background: IGF-1 up-regulates PC proliferation and invasiveness through activation of PI3K/Akt signaling pathway and down-regulates PTEN. We investigated IGF-1 expression in tissue and blood as potential predictive markers in phase II study of IGF1R-directed monoclonal antibody, MK-0646 in APC. Prior phase I established the MTD of MK0646 at 5 mg/kg with gemcitabine (G) and erlotinib (E) and 10 mg/kg with G alone. Methods: Patients (pts) with stage IV, previously untreated APC, ECOG PS 0-1, adequate hematologic and organ function were enrolled. Arm A: G 1,000 mg/m2 over 100 min, weekly x 3, MK-0646 weekly x 4; Arm B: G 1000 mg/m2 and MK-0646 + E 100 mg daily. Arm C (control) was G 1,000 mg/m2 + E 100 mg. Cycles were repeated every 4 weeks. Pts were equally randomized in the 3 arms. Primary study objective was progression-free survival (PFS). Pre-treatment peripheral blood samples were measured for IGF-1 level by ELISA; archival core biopsies were analyzed for IGF-1 mRNA expression. RNA extraction from FFPE samples used Roche Transcriptor First Strand cDNA Synthesis Kit. TaqMan PreAmp technique was used to amplify target cDNA prior to TaqMan RT-PCR analysis. Cox proportional hazards model for PFS analyzed the interaction between tissue IGF-1 expression and treatment. Results: 50 pts were enrolled (A=15, B=16,C=16 pts, 3 ineligible). Median PFS of arms A, B and C were 5.5 months (95% CI: 3.9 – NA), 3.0 months (95% CI:1.8 – 5.6) and 2.0 months (95% CI: 1.8 – NA), respectively (log-rank test; p = 0.17). Median OS of A was 11.3 months (95% CI: 8.9 – NA), B 8.9 months (95% CI: 5.3 – NA) and C 5.7 months (95% CI: 2.0 – NA) (log-rank test; p = 0.44). 35 archival core biopsies were analyzed, 21 had adequate tissue for analysis. Using a Multivariable Cox proportional hazards model for PFS, where IGF-1 was dichotomized at the median, there was a 76% reduction in the risk of disease progression or death in arm A as compared with the control (arm C) at high IGF-1 level (p = 0.16). When IGF-1 was fitted as a continuous variable, this reduction was 96% (p = 0.08). There was no correlation between tissue and serum IGF-1. Conclusions: Tissue expression of IGF-1 level may represent a promising predictive biomarker for IGF1R-directed therapy in APC.

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