Evaluation of lesion-based response at 12 weeks (LBR12) of treatment (Rx) in metastatic colorectal cancer (mCRC): Findings from 9,092 patients (pts) in the ARCAD database.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 612-612
Author(s):  
Fang-Shu Ou ◽  
Yiyue Lou ◽  
Eric Van Cutsem ◽  
Leonard Saltz ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Progressive Disease ◽  
Egfr Inhibitor ◽  
Cox Models ◽  
Treatment Regimens ◽  
Vegf Inhibitor ◽  
Predicting Outcome ◽  
Ecog Ps

612 Background: mCRC is a heterogeneous disease leading to possible disparate responses among lesions in a single pt. This study assesses the heterogeneity of lesion responses and evaluates the prognostic value of LBR12 and its mortality risk discrimination beyond RECIST responses. Methods: Pts with ≥ 2 lesions and no new lesions at 12 weeks (wks) were eligible. For each pt, after 12 wks of Rx, each lesion was categorized as progressive disease (L-PD: ≥20% increase in the longest diameter [LD]), partial response (L-PR: ≥30% decrease in LD), or stable disease (L-SD: neither L-PD nor L-PR). LBR12 was defined, per patient, by the combination of lesion responses: homogeneous LBR12 (L-PD, L-SD, L-PR only) and heterogeneous LBR12 (mixture of L-PD/L-SD, L-PD/L-PR, L-SD/L-PR). LBR12 and overall survival (OS) were correlated using stratified multivariate Cox models after adjusting for age, gender, and ECOG PS. Results: Among 9,092 mCRCs (Rx: chemo alone 44%; chemo + VEGF inhibitor [VEGFi] 42%; chemo + EGFR inhibitor [EGFRi] 10%) from 16 1st-line studies. Median OS: 2.2 years. Per RECIST at 12 wks, CR 0%; PR 36.1%; SD 60.9%; PD 3.0%. Responses in 52% were heterogeneous (Table). VEGFi and EGFRi treated pts had the highest rate of L-SD/L-PR (45%) and L-PR only (22%) status, respectively. Median OS increased monotonically across pts with more L-PRs and fewer L-PDs (Table). Pts with L-SD/L-PR status, among which 51% had SD per RECIST, had longer OS than those with L-SD only status (HRadj.= .81, padj.< .0001), but shorter OS than those with L-PR only status (HRadj.= 1.46, padj.< .0001). Pts with L-PD/L-SD status, among which 71% were SD per RECIST, had shorter OS than those with L-SD only status (HRadj.= 2.22, padj.< .0001). These associations were consistent across treatment regimens. Conclusions: The lesion-based response captures the heterogeneity of within pt lesion responses and provides refinement in predicting outcome beyond RECIST response at 12 wks. [Table: see text]

A retrospective analysis of real-world time on treatment and overall survival in patients with metastatic colorectal cancer receiving cetuximab in third line.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15575-e15575
Author(s):  
Wambui Gathirua-Mwangi ◽  
Tony Yang ◽  
Taha Khan ◽  
Yixun Wu ◽  
Manuel Afable
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Retrospective Analysis ◽  
Real World ◽  
Index Date ◽  
Geographic Region ◽  
P Value ◽  
Cox Models ◽  
Treatment Regimens ◽  
Third Line

e15575 Background: Colorectal cancer (CRC) is the 3rd leading cause of cancer-related deaths in the US. Anti-epidermal growth factor receptor agents improve outcomes of patients with metastatic CRC (mCRC) and are used in multiple lines of therapy. However, real-world time on treatment (TOT) and overall survival (OS) of cetuximab in third-line (3L) have not been described. Therefore, we sought to evaluate TOT, OS, and associated factors in a retrospective study. Methods: A total of 617 patients diagnosed with mCRC and received 3L treatment with cetuximab containing regimens regardless of prior therapies were selected from the nationwide Flatiron electronic health record database (January 2013 - August 2020). TOT was defined as the time from initiation of cetuximab in 3L (index date), to the last recorded date of cetuximab administration. End of therapy was defined if the patients progressed to subsequent line of therapy, or had a record of death. OS was calculated from the index date to date of death or censored to last visit date available. The Kaplan-Meier estimates, and stepwise Cox models were adapted to identify and calculate hazard ratios (HR), and 95% confidence intervals (CI) for factors associated with TOT and OS. Results: Majority of patients receiving 3L treatment with cetuximab containing regimens were: treated in the community setting (96%), less than 65 years old (58%), overweight with a median body mass index (BMI) of 26.2 kg/m² and, received FOLFOX regimens in 1L (46%) and FOLFIRI in 2L (47%). The most common cetuximab containing regimens were cetuximab+irinotecan (36%) and cetuximab+FOLFIRI (34%) and cetuximab monotherapy. The median TOT (mTOT) for patients receiving 3L cetuximab containing regimens was 3.48 months (median interquartile range (mIQR) 3.02-4.17). Higher BMI (obese vs. underweight HR = 0.44, 95% CI 0.28-0.68) was associated with a longer mTOT, while having an ECOG score ≥1 was associated with a shorter mTOT (vs. ECOG = 0, HR = 1.37, 95% CI 1.10-1.72). Also, of all cetuximab containing regimens in 3L cetuximab + FOLFIRI (vs. cetuximab monotherapy) was associated with a longer mTOT (4.63 months, mIQR 3.45-5.55). The median OS (mOS) for patients receiving 3L cetuximab containing regimens was 11.99 months (mIQR 10.87-12.94). Similarly, higher BMI (obese vs. underweight HR = 0.25, 95% CI 0.16-0.40) and 3L cetuximab + FOLFIRI (mOS= 14.3 months, mIQR 11.66-16.85) vs. cetuximab monotherapy were associated with a longer mOS. OS did not differ by patient’s geographic region (South vs Midwest, p-value 0.35). Conclusions: In this real-world retrospective analysis cetuximab + irinotecan and cetuximab + FOLFIRI were the most common 3L cetuximab regimens. The most common treatment regimens in 1L and 2L were FOLFOX and FOLFIRI respectively. Overall, BMI and treatment regimens received in 3L were associated with mTOT and mOS.

Overall survival based on MSI and BRAF mutation status for stage II/III colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 132-132
Author(s):  
Sophiya Karki ◽  
Rashna Madan ◽  
Sarah Schmitt ◽  
Ziyan Y. Pessetto ◽  
Andrew K. Godwin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Microsatellite Instability ◽  
Median Survival ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Stage Ii ◽  
Age At Diagnosis ◽  
Mutation Status ◽  
Braf Mutant

132 Background: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the United States. Some of the poor prognostic factors for metastatic CRC (mCRC) include BRAF V600E mutation and microsatellite instability (MSI) that result from mutation or loss of mismatch-repair genes. While the prognostic value of MSI-high CRC for early-stage patients treated with resection and adjuvant chemotherapy is favorable, the prognostic value of BRAF mutation is still unclear. Furthermore, the impact of BRAF mutation with concurrent microsatellite instability on overall survival has not been well investigated. Methods: Here, we collected BRAF mutation status and MSI status of stage II/III CRC patients (n=106) treated at the University of Kansas Cancer Center between September 2009 and July 2020 and compared overall survival between 4 subtypes:MSI-H/BRAF mutant (n=16), MSS/BRAF mutant (n=4), MSI-H/BRAF WT (n=17) and MSS/BRAF WT (n=69), further stratifying patients by age at diagnosis and tumor location. Molecular data were obtained from molecular oncology laboratory as PCR or IHC-based or acquired from outside records. Subgroup analyses were done for stage II and stage III cancers. Results: Table shows the patient characteristics. From our preliminary analysis, MSI-H CRC was found to be primarily a right-sided tumor (MSI-H/BRAF mutant: 94% and MSI-H/BRAF WT 76%). On the contrary, MSS CRC had a more heterogenous localization, spanning left colon, right colon and rectum. In our patient cohort, median survival was not reached for stage II patients whereas for stage III patients, BRAF mutation was associated with poor median survival irrespective of MSI status (MSS/BRAF mutant: 27 months and MSI-H/BRAF mutant 29 months). Median overall survival was found to be 87 months, not reached, 27 months and 29 months for MSS/BRAF WT, MSI-H/BRAF WT, MSS/BRAF mutant and MSI-H/BRAF mutant, respectively. Although associated with poor survival, MSI-H/BRAF mutant displayed later age at diagnosis (mean age 73) compared to MSS/BRAF mutant (mean age 60, p-value<0.029). Conclusions: Our finding suggests that BRAF mutation has poor prognosis even at earlier stages of the disease and that MSS/BRAF mutation, in particular, has the worst prognostic features. These findings highlight the need for BRAF-targeted therapy for CRC at any stage. Due to small sample size, however, our results warrant validation in a larger cohort. [Table: see text]

scholarly journals Association of STMN1 with survival in solid tumors: A systematic review and meta-analysis

2019 ◽  
Vol 34 (2) ◽  
pp. 108-116
Author(s):  
Dan Zhang ◽  
Lizhen Dai ◽  
ZengXi Yang ◽  
XiChen Wang ◽  
Yin LanNing
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Endometrial Cancer ◽  
Solid Tumors ◽  
Prognostic Value ◽  
Web Of Science ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Poor Overall Survival

Background: The prognostic value of Stathmin 1 (STMN1) in malignant solid tumors remains controversial. Thus, we conducted this meta-analysis to summarize the potential value of STMN1 as a biomarker for predicting overall survival in patients with solid tumor. Methods: We systematically searched eligible studies in PubMed, Web of Science, and EMBASE from the establishment date of these databases to September 2018. Hazard ratio (HR) and its 95% confidence interval (CI) was used to assess the association between STMN1 expression and overall survival. Results: A total of 25 studies with 4625 patients were included in this meta-analysis. Our combined results showed that high STMN1 expression was associated with poor overall survival in solid tumors (HR = 1.85, 95% CI 1.55, 2.21). In general, our subgroup and sensitivity analyses demonstrated that our combined results were stable and reliable. However, from the results of the subgroups we found that high STMN1 expression was not related to overall survival in colorectal cancer and endometrial cancer anymore, suggesting that much caution should be taken to interpret our combined result, and more studies with large sample sizes are required to further explore the prognostic value of STMN1 expression in the specific type of tumors, especially colorectal cancer and endometrial cancer. Conclusions: STMN1 could serve as a prognostic biomarker and could be developed as a valuable therapeutic target for patients with solid tumors. However, due to the limitations of the present meta-analysis, this conclusion should be taken with caution. Further studies adequately designed are required to confirm our findings.

BRAF and KRAS mutations as additional risk factors in the context of clinical parameters of patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3522-3522
Author(s):  
Vlad Calin Popovici ◽  
Eva Budinska ◽  
Arnaud Roth ◽  
Fred Bosman ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Tumor Site ◽  
Kras Mutations ◽  
P Values ◽  
Significance Level ◽  
Survival After Relapse

3522 Background: The BRAF and KRAS mutations have been proposed as prognostic markers in colorectal cancer (CRC). Of them, only the BRAF V600E mutation has been validated as prognostic for overall survival and survival after relapse, while the value of KRAS mutation is still unclear. Methods: In a cohort of 1423 stage II-III patients from the PETACC-3 clinical trial, the prognostic value of the BRAF and KRAS mutations was retrospectively assessed in all possible stratifications defined by the 5 factors (T and N stage, tumor site and grade, and microsatellite instability status), by log rank test for overall survival (OS), relapse-free survival (RFS), and survival after relapse (SAR). The presence of interactions was tested by Wald test. The significance level was set to 0.01 for Bonferroni-adjusted p-values (P*), and a second level for a trend towards statistical significance was set at 0.05 for unadjusted p-values (P). Results: BRAF mutation was a marker of poor OS only in microsatellite stable (MSS) and left-sided tumors, with no prognostic value in microsatellite instable (MSI-H) or right-sided tumors. In MSS/left-sided tumors, BRAF mutation represents a marker of higher risk than previously reported: OS HR=6.4 [95% CI: 3.6-11.5], P* < 0.0001. For SAR, BRAF was prognostic in more stratifications, with higher risk in MSS/left-sided tumors (HR=3.9 [95% CI: 2.1-7.2], P* = 0.0002) than in MSS/right-sided (HR=2.3 [95% CI: 1.2-4.4], P=0.01). A novel observation was that BRAF mutation was prognostic also for RFS, but only in MSS/left-sided tumors (HR=3.6 [95% CI:2-6.3], P*=0.0005]). Additionally, heterogeneity in OS and RFS among BRAF mutants was observed. In general, KRAS mutation did not reach the significance level required, but showed a trend to become a prognostic marker for RFS in MSS tumors with early lymph node involvement (N1) (HR=1.6 [95% CI:1.1-2.2], P=0.01). Conclusions: The prognostic utility of the BRAF and KRAS mutations has to be interpreted in the context of other factors. For the BRAF mutation, a clear interaction with MSI status and tumor site was observed, with BRAF mutation indicating a much higher risk in MSS/left-sided tumors than previously considered.

Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 534-534
Author(s):  
Hui-li Wong ◽  
Kathryn M Field ◽  
Jeanne Tie ◽  
Suzanne Kosmider ◽  
Jeremy David Shapiro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Clinical Care ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Routine Practice ◽  
Ecog Ps ◽  
To Receive

534 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centres. Results: Of the 679 patients entered, 129 (19.0%) had an ECOG PS ≥ 2. In total, 77 (11.3%) were PS 2, 41 (6.0%) PS 3 and 11 (1.6%) PS 4. Chemotherapy was administered to 55 (71.4%) PS 2 and 15 (36.6%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (55.0% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (38.0% vs 71.6%, p<0.0001) or bevacizumab (15.5% vs 46.9%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 31.2, 9.0, 3.0 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.8 vs 4.1 months for untreated patients, p<0.0001). At one and two years, 22 (31.4%) and 8 (11.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.

Real world eligibility of treatment-refractory stage IV colorectal cancer patients for palliative intent regorafenib monotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15007-e15007 ◽  
Author(s):  
Arkhjamil Angeles ◽  
Wayne Hung ◽  
Winson Y. Cheung
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Real World ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Correct Trial ◽  
Eligibility Criteria ◽  
Ecog Ps

e15007 Background: The CORRECT trial demonstrated overall survival benefits of regorafenib monotherapy in patients with metastatic colorectal cancer (CRC) who were refractory to prior chemotherapy and biological therapy. However, stringent criteria used to determine treatment eligibility in the trial setting may limit its external validity in the real world. We aimed to examine treatment attrition rates and eligibility of regorafenib in routine clinical practice. Methods: All patients diagnosed with metastatic CRC between 2009 and 2014 who received 2 or more lines of systemic therapy at the British Columbia Cancer Agency were identified. During the study timeframe, cetuximab (cmab) and panitumumab (pmab) were only used in the chemo-refractory setting. Data on clinical factors, pathological variables and outcomes were ascertained and analyzed. Eligibility was defined based on criteria outlined in the CORRECT trial. Results: A total of 391 patients were included among whom only 39% were considered eligible for regorafenib. Median age was 61 (range 22-84) years. 247 (63%) were men, 305 (78%) were Caucasian, and 237 (60%) had a colonic primary. The disease burden at diagnosis was high: 267 (81%) had lymph node involvement, and 225 (59%) had distant metastases. In patients previously treated with cmab, main reasons for regorafenib ineligiblity were Eastern Cooperative Oncology Group performance status (ECOG PS) > 1 (26.9%), aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) (6.5%), and arterio-venous thrombotic or embolic events in the preceding 6 months (6.5%). In the group treated with pmab previously, main reasons for ineligibility were ECOG PS > 1 (46.6%), total bilirubin > 1.5 x ULN (14.1%), and thrombotic or embolic events in the past 6 months (5.7%). Additional analyses showed that regorafenib-eligible patients had increased median overall survival compared to ineligible patients (44.0 vs 37.1 months, P= 0.028). Conclusions: The strict trial eligibility criteria disqualified the majority of real world patients with metastatic CRC for regorfenib. As ineligibility predicts poorer outcomes, trials aimed at serving protocol-ineligible patients are warranted.

scholarly journals Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer: an updated systematic review and meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yen-Lin Yu ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Pre Treatment ◽  
Disease Free

Abstract Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

scholarly journals Efficacy of Panitumumab and Cetuximab in Patients with Colorectal Cancer Previously Treated with Bevacizumab; a Combined Analysis of Individual Patient Data from ASPECCT and WJOG6510G

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1715
Author(s):  
Hiroya Taniguchi ◽  
Takeharu Yamanaka ◽  
Daisuke Sakai ◽  
Kei Muro ◽  
Kentaro Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Clinical Trial Registration ◽  
Cox Models ◽  
Exon 2 ◽  
Free Survival ◽  
Previously Treated

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).

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