scholarly journals What is a clinically meaningful survival benefit in refractory metastatic colorectal cancer?

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
Y. J. Ko ◽  
M. Abdelsalam ◽  
P. Kavan ◽  
H. Lim ◽  
P. A. Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Clinical Benefit ◽  
Policy Decision ◽  
Standard Of Care ◽  
Current Standard ◽  
Cancer Treatments ◽  
Medical Oncologists ◽  
Definition Of

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment.    For metastatic colorectal cancer (mcrc), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory mcrc.    It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory mcrc. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment’s effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.

scholarly journals Overall Survival As the Outcome for Randomized Clinical Trials With Effective Subsequent Therapies

2011 ◽  
Vol 29 (17) ◽  
pp. 2439-2442 ◽  
Author(s):  
Edward L. Korn ◽  
Boris Freidlin ◽  
Jeffrey S. Abrams
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Randomized Clinical Trial ◽  
Clinical Benefit ◽  
Randomized Clinical Trials ◽  
Experimental Treatment ◽  
Standard Of Care ◽  
Current Standard ◽  
End Point

We review how overall survival (OS) comparisons should be interpreted with increasing availability of effective therapies that can be given subsequently to the treatment assigned in a randomized clinical trial (RCT). We examine in detail how effective subsequent therapies influence OS comparisons under varying conditions in RCTs. A subsequent therapy given after tumor progression (or relapse) in an RCT that works better in the standard arm than the experimental arm will lead to a smaller OS difference (possibly no difference) than one would see if the subsequent therapy was not available. Subsequent treatments that are equally effective in the treatment arms would not be expected to affect the absolute OS benefit of the experimental treatment but will make the relative improvement in OS smaller. In trials in which control arm patients cross over to the experimental treatment after their condition worsens, a smaller OS difference could be observed than one would see without cross-overs. In particular, use of cross-over designs in the first definitive evaluation of a new agent in a given disease compromises the ability to assess clinical benefit. In disease settings in which there is not an intermediate end point that directly measures clinical benefit, OS should be the primary end point of an RCT. The observed difference in OS should be considered the measure of clinical benefit to the patients, regardless of subsequent therapies, provided that the subsequent therapies used in both treatment arms follow the current standard of care.

Lymphocyte-to-monocyte ratio (LMR) compared to sidedness of primary tumor to predict outcome of anti-EGFR monotherapy in metastatic colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 809-809
Author(s):  
Lucjan Wyrwicz ◽  
Maciej Temnyk ◽  
Sebastrian Rybski ◽  
Mariola Winiarek ◽  
Katarzyna Kokoszyńska
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Standard Of Care ◽  
Cancer Center ◽  
Time To Failure ◽  
Site Location ◽  
Prognostic Effect ◽  
Lymphocyte To Monocyte Ratio ◽  
Left And Right

809 Background: In RAS-wild type metastatic colorectal cancer (mCRC) treatment with cetuximab or panitumumab is the standard of care. Previously, the association between overall survival (OS) and inflamatory biomarkers were reported in several studies in mCRC (NLR, LMR). According to recent observations, primary site location can predict the superior outcome of anti-EGFR agents in first line of treatment. Here we test the relationship between inflamatory biomarkers and sidedness on outcomes of anti-EGFR therapy. Methods: Total 186 consecutive patients treated with panitumumab (n = 106) or cetuximab (n = 80) in monotherapy in third or following lines of palliative treatment were identified via electronic survey of medical records of Maria Sklodowska-Curie Memorial Cancer Center, Poland. All identified patients were treated within the state reimbursment programme with pre-specified inclusion criteria (including ECOG 0-2 mCRC, failure of previous irinotecan, oxaliplatin and fluoropiridine, all RAS-wt tumors) and treatment was administered until RECIST progression. The pretreatment inflamatory biomarkers (NLR, dNLR, LMR, PLR) were obtained for all patients. Results: Median overall survival of the cohort was 31.5 months when calculated from the start of treatment, with no difference for left- and right-sided tumors (31.8 m. vs 29.5 m.; p = 0.58). In third line treatment no difference in PFS between left- and right-sided tumors were observed (p = 0.22; PFSleft 4.82 m. vs PFSright 3.44 m.). No prognostic effect of either biomarker was noted on OS or time to failure of first two lines of treatment. Only a high lymphocyte-to-monocyte ratio (LMR > 2.6) and low derived neutrocyte-to-lymphocyte ratio (dNLR < 3.0) were associated with longer PFS on anti-EGFR treatment (5.5 m. in LMR > 2.6; 2.5 m. in LMR < 2.6; HR 0.53; p = 0.008). Notable, the patients with LMR > 2.6 were more likely to be diagnosed with left sided tumor (p < 0.001; 54% and 15% of left- and right-sided tumors respectively). Conclusions: High limfocyte-to-monocyte ratio may indicate the potential subpopulation of patients which can benefit mostly from anti-EGFR treatment in monotherapy in the refractory setting.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada

2020 ◽  
Vol 16 (5) ◽  
pp. e425-e432 ◽  
Author(s):  
Todd A. Yezefski ◽  
Dan Le ◽  
Leo Chen ◽  
Caroline H. Speers ◽  
Shasank Chennupati ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
British Columbia ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Systemic Therapy ◽  
Survival Data ◽  
De Novo ◽  
Tumor Resection ◽  
Care Utilization ◽  
Western Washington

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada’s single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.

scholarly journals Subsequent anti-VEGF therapy after first-line anti-EGFR therapy improved overall survival of patients with metastatic colorectal cancer

2018 ◽  
Vol Volume 11 ◽  
pp. 465-471 ◽  
Author(s):  
Tianzhu Qiu ◽  
Wensen Chen ◽  
Ping Li ◽  
Jing Sun ◽  
Yanhong Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
First Line ◽  
Anti Vegf
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