Association of morphologic response with progression free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 743-743
Author(s):  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Hideyuki Hayashi ◽  
Hiraku Fukushima ◽  
Takashi Kato ◽  
...  

743 Background: It was reported that an optimal morphologic response to preoperative chemotherapy was associated with better overall survival (OS) in patients (pts) with colorectal liver metastases (CLM). We investigated association of morphologic response with progression free survival (PFS) in pts with unresectable CLM from HGCSG0802 observational cohort study in pts with mCRC treated with first-line bevacizumab (BV)-based chemotherapy. Methods: The objective of HGCSG0802 was to evaluate PFS, OS, time to treatment failure (TTF), response rate (RR), safety, etc. The key eligibility criteria were evaluable lesions, older than 20 years old, ECOG PS 0-2. Pts with CLM underwent contrast-enhanced CT at the start and every 8-weeks of BV-based chemotherapy. In this analysis, three blinded, independent radiologists evaluated images for morphologic response, based on metastases changing from heterogeneous masses with ill-defined margins into homogeneous hypoattenuating lesions with sharp borders. Association of morphologic response and pts characteristics, RR, and PFS were evaluated. PFS was analyzed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Of 108 pts (the full analysis set), 73 pts with CLM were evaluable for morphologic criteria. Eighteen pts (24.7%) had optimal morphologic response (OR), 31 (42.5%) had incomplete (IR), and 24 (32.9%) had no response (NR). The pts characteristics between those with OR, IR and NR were generally balanced. The median TTF was 7.2 months in NR versus 7.2 months in IR versus 6.8 months in OR (HR (OR/NR) = 0.91, HR (OR/IR) = 0.90; p = 0.93). RR was 77.8% in OR versus 64.5% in IR and 58.3% in NR (p = 0.528). The median PFS was 8.3 months in NR versus 8.5 months in IR versus 9.1 months in OR (HR (OR/NR) = 0.72, HR (OR/IR) = 1.04; p = 0.420). Conclusions: In this analysis, morphologic response might not be a prognostic marker in first-line BV-based chemotherapy in pts with CLM.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5042-5042
Author(s):  
S. Patil ◽  
R. A. Figlin ◽  
T. E. Hutson ◽  
M. D. Michaelson ◽  
S. Négrier ◽  
...  

5042 Background: Sunitinib demonstrated superior progression-free survival (PFS; the primary endpoint) over interferon-alfa (IFN-α) as first-line mRCC therapy (NEJM 2007;356:115). Median overall survival (OS) with sunitinib compared to IFN-α was: 26.4 vs. 21.8 months (HR=0.821; P=0.051 by unstratified log-rank test; Proc ASCO 2008;26, May 20 suppl; abstr 5024). An analysis of prognostic factors for OS was performed on data from this trial. Methods: 750 treatment-naïve mRCC patients were randomized 1:1 to receive sunitinib or IFN-α. By Cox proportional hazards model, selected pretreatment variables were evaluated univariately and in a multivariate model for each treatment arm. Multivariate models for each treatment arm were based on a stepwise algorithm with a type I error of 0.25 for entry and 0.15 for elimination. Further elimination was applied to identify variables significant at P<0.05. Results: In multivariate analysis of sunitinib patients, factors associated with longer OS include: interval from diagnosis to treatment ≥1 yr, ECOG PS of 0, lower corrected calcium, absence of bone metastases, lower lactic dehydrogenase (LDH), and higher hemoglobin (Hgb) ( table ). For the IFN-α treatment arm, male gender, absence of bone or lymph node metastases, lower LDH, higher Hgb, lower corrected calcium, higher neutrophil count, and interval from diagnosis to treatment ≥1 yr were associated with longer OS. Conclusions: For patients in the sunitinib treatment arm, prognostic factors identified were similar to the factors previously identified in the MSKCC risk groups (J Clin Oncol 2002;20:289). Additional prognostic factors were identified for the IFN-α arm. Further studies are warranted to independently validate these findings as well as to identify tumor-specific prognostic factors. [Table: see text] [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16001-e16001
Author(s):  
Yuxian Bai ◽  
Shukui Qin ◽  
Jin Li ◽  
Yanhong Deng ◽  
Lei Yang ◽  
...  

e16001 Background: The FRESCO phase 3 trial demonstrated a significant survival benefit with fruquintinib vs. placebo in the third-line or later therapy of mCRC patients. CEA levels are widely used in conjunction with imaging to monitor response to systemic therapy in patients with mCRC. Herein, we undertook post-hoc analyses of FRESCO patient data to investigate the early changes in CEA during treatment, as well as potential relationships with efficacy parameters. Methods: Patients were included if baseline CEA was abnormal according to local lab reference range. Serum CEA levels were measured at baseline and Day 1 of each cycle (except for Cycle 1). Early CEA change was analyzed at first radiological evaluation (C3D1, Week 8), CEA response was defined as ≥ 50% decrease from baseline, and CEA progression was defined as ≥ 100% increase from baseline. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated through Cox proportional hazards model; p-value was generated from log rank test. Results: 88.4% (245/277) and 94.9% (130/137) of patients had an abnormal baseline CEA in the fruquintinib group and placebo group, respectively. Median baseline CEA values were similar between treatment groups. After 2 cycles of treatment, the proportion of patients had CEA response was significantly higher in the fruquintinib group than placebo group (30.0% vs. 1.3%, p < 0.001). In the fruquintinib group, patients with early CEA response (n = 63) had longer median OS (12.8 vs. 7.8 months, HR = 0.45, p < 0.001) and median PFS (5.6 vs. 3.7 months, HR = 0.49, p < 0.001) than patients without (n = 147). 66.7% (140/210) of patients in fruquintinib group had stable disease (SD), and fruquintinib in those patients with concomitant CEA response exhibited a significantly greater OS benefit than with CEA progression (14.4 vs. 8.7 months, HR = 0.38, p = 0.004). Conclusions: Fruquintinib increased early CEA response. CEA response at first radiological evaluation after cycle 2 could be considered as a predictor for better OS and PFS. Among patients with SD at first evaluation, those with CEA response seems benefit more from fruquintinib. Clinical trial information: NCT02314819 .


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 781-781
Author(s):  
Ayumu Hosokawa ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kazuteru Hatanaka ◽  
Yasushi Tsuji ◽  
...  

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1072-1072
Author(s):  
Siu W. Lam ◽  
Steffen M. de Groot ◽  
Aafke H. Honkoop ◽  
Nienke M. Nota ◽  
A. Jager ◽  
...  

1072 Background: In the randomized phase II ATX trial, pts with HER2-negative LR/MBC were treated with first-line AT or ATX. We determined the prognostic value for outcome of VEGF-A, ANG2 and sTIE2 measured at baseline on cycle 1 day 1 (C1D1) and after cycle 1 (C2D1). Methods: 312 pts were randomized in 1:1 ratio to AT (T 90 mg/m2 on d1, 8, 15 and A 10 mg/kg on d1, 15 q4w x 6 cycles, followed by A 15 mg/kg on d1 q3w for next cycles) or ATX (T 90 mg/m2 on d1, 8, A 15 mg/kg on d1 and X 825 mg/m2bid on d1–14 q3w x 8 cycles, followed by the same dose of A and X q3w for next cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), response duration (RD), overall survival (OS) and safety. Plasma proteins on C1D1 (N = 173) and on C2D1 (N = 142) were measured by ELISA. The association of protein levels (continuous variable) with PFS and OS was evaluated by Cox proportional hazards model and Martingale residual plot. Results: At a median follow-up of 39 months (mo), there were 292 PFS events and 242 deaths. ATX significantly improved PFS as compared to AT (median 11 vs. 8.4 mo, stratified HR = 0.52; 95% CI, 0.41 – 0.67; P < .001). The confirmed ORR in measurable disease (N = 268) was 67% in ATX vs. 50% in AT. Median RD was 6.4 mo (95% CI, 6.1 – 8.3) in ATX v 5.4 mo (95% CI, 5.1 – 6.0) in AT. Median OS was 24.1 mo in ATX vs. 23.1 mo in AT (P= .44). The aselected ‘biomarker’ cohort (N = 173) and overall trial cohort had similar baseline characteristics. ANG2 on C1D1 moderately correlated with sTIE2 on C1D1 (Pearson’s r = .44, P < .001). High ANG2 on C1D1 was significantly associated with poor OS (HR = 1.6; 95% CI, 1.1 – 2.3; P = .01), but not with poor PFS (HR = 1.3; 95% CI, 1.0 – 1.3; P = .07). ANG2 on C2D1 was not significantly associated with OS (HR = 1.55; 95% CI, 0.99 – 2.4; P = .057) or with PFS (P= .6). sTIE2 and VEGF-A were not associated with outcome. All pts had very low levels of free VEGF-A on C2D1 (median 8 pg/ml). Conclusions: In HER2-negative LR/MBC, ATX is more effective (PFS, ORR and RD) than AT. A very high plasma level of ANG2 at baseline indicates a high risk for poor survival. Clinical trial information: NTR1348.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1001-1001
Author(s):  
Dennis J. Slamon ◽  
Patrick Neven ◽  
Stephen K. L. Chia ◽  
Guy Heinrich Maria Jerusalem ◽  
Michelino De Laurentiis ◽  
...  

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]


2020 ◽  
Vol 31 (1) ◽  
pp. 110-113
Author(s):  
Jole Ventriglia ◽  
Immacolata Paciolla ◽  
Carmela Pisano ◽  
Rosa Tambaro ◽  
Sabrina Chiara Cecere ◽  
...  

BackgroundChemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described.ObjectiveTo examine the incidence, duration, and reversibility of arthralgia.Patients and methodsA retrospective analysis was performed to describe the occurrence and outcome of arthralgia in 114 patients with advanced ovarian cancer, given first-line treatment with a combination of carboplatin, paclitaxel, and bevacizumab. Statistical analysis was performed to investigate a possible prognostic role of arthralgia, with progression-free survival as endpoint.Results47 of 114 patients (41%) developed arthralgia during therapy. All patients had grade 1 or grade 2 arthralgia. Toxicity persisted after the end of bevacizumab in 17/47 patients (36%). Median progression-free survival for patients without arthralgia was 18 months (95% CI 14 to 24) compared with 29 months (95% CI 21 to not reached) for patients experiencing arthralgia (p=0.03). In order to avoid possible biases related to treatment duration, a multivariable Cox proportional hazards model including toxicity as a time dependent variable and age, stage, and residual disease after primary surgery was performed. In this model no variable showed a statistically significant association with progression-free survival.ConclusionA high incidence of arthralgia (41%) was found and although rogression-free survival was worse for those patients who developed arthralgia, this was not maintained on multivariate analysis. Guidelines for treatment of this adverse event are needed.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 110-110 ◽  
Author(s):  
Sean Khozin ◽  
Mark S. Walker ◽  
Monika Jun ◽  
Li Chen ◽  
Edward Stepanski ◽  
...  

110 Background: Anecdotal and early evidence suggest ICIs are being used in patients with advanced malignancies and history of AD, despite such patients being typically excluded from traditional clinical trials. We compared the outcomes of patients with or without AD, all of whom had ICI treatment for aNSCLC. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in ASCO’s CancerLinQ. Patients with Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 visits from Jan 2011 to Nov 2018 were included. AD status prior to ICI treatment was identified using ICD-9/ICD-10 codes or AD medications (including steroids). Symphony claims data were linked via tokenization to build cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS) and overall survival (OS) were compared across the two cohorts using the log-rank test. Cox Proportional Hazards Model was used to adjust for covariates. Adverse events (AEs) were compared using Chi-Square and Fisher’s Exact Test. Active AD was defined as evidence of autoimmune disease in the year prior to starting ICIs. Results: Among 2425 patients with aNSCLC treated with ICIs, AD was present in 22% (N=538). Median OS in all patients was 12.4 months (95% CI 11.3-13.5). TTD, TTNT, rwPFS and OS did not differ between the two cohorts (Table). There was no association between AD status and outcomes. There was no increased incidence of AEs in the AD group; however a sub-analysis among patients with active AD showed higher rates of select AEs including endocrine, GI and blood disorders. Conclusions: This analysis demonstrates that patients with evidence of AD prior to receiving ICI have similar outcomes compared to patients with no evidence of AD. Further research is needed to better understand the impact of active AD on the risk of AEs and patient outcomes. [Table: see text]


2017 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Reza Mehrazin ◽  
Essel Dulaimi ◽  
Robert G. Uzzo ◽  
Karthik Devarjan ◽  
Jianming Pei ◽  
...  

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.


2021 ◽  
Vol 7 (1) ◽  
pp. 00543-2020
Author(s):  
Balázs Csoma ◽  
András Bikov ◽  
Ferenc Tóth ◽  
György Losonczy ◽  
Veronika Müller ◽  
...  

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.


2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Hina Saeed ◽  
David M. King ◽  
Candice A. Johnstone ◽  
John A. Charlson ◽  
Donald A. Hackbarth ◽  
...  

Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS.Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used.Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p<0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p=0.08). Preoperative radiation (RT) (p=0.01) and use of any RT for UE (p=0.003) led to improved PFS. On MVA, preoperative RT (p=0.04) and performance status (p=0.01) led to improved PFS.Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.


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