An Observational Study on The Correlation Between Time of Initiation of Avastin (Bevacizumab) Treatment And Progression-Free Survival in Patients With Colorectal Cancer (CRONOS 1)
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2100846 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Background: Using progression-free survival (PFS)2, time from randomization to 2nd disease progression or death, is proposed as a surrogate for overall survival (OS) in oncology clinical trials. We used published data from solid tumor trials to assess whether PFS2 and OS are correlated. Methods: A literature search identified studies that reported PFS, PFS2, and OS. Two reviewers screened for eligibility, and documented PFS2, PFS or time from 1st to 2nd disease progression or death and OS. Correlation between PFS2 and OS was assessed using: (1) Kendall's Tau + Pearson's correlation coefficient in randomized controlled trials (RCTs); (2) Meta-analysis with the random effects model to compute the pooled correlation of PFS2 and OS. Results: Overall, 133 studies met search criteria, 15 (28 arms) had complete PFS2 and OS data in ovarian, gastric, colorectal, prostate, lung, renal and breast cancers. A positive correlation for PFS2 and OS was found for all 15 studies (Kendall's Tau = 0.7 [95% CIs 0.54, 0.78]); 10 RCTs (Pearson's correlation coefficient = 0.86); and meta-analysis from 7 trials (pooled Spearman's correlation coefficient = 0.84 [p = 0.0001; 95% CIs 0.71, 0.96]). Conclusions: In this retrospective analysis PFS2 strongly correlates with OS supporting the use of PFS2 to measure long-term clinical benefit when OS cannot be assessed.
| S-EPMC7456898 | biostudies-literature
Project description:BackgroundTrastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity.MethodsHERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy.ResultsOf 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks.ConclusionThe correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy.
| S-EPMC8091175 | biostudies-literature
Project description:Cancer progression results from a complex interplay between tumor cells and the extracellular milieu. In breast carcinoma, the stromal microenvironment has been suggested to play a major role in promoting tumor growth, progression, and invasion. The stroma of 154 resected specimens of invasive breast carcinoma of no special type was quantified using a digital image analyzer. Statistical analyses were performed between the quantity of stroma and survival, as well as between progression-free survival and clinicopathological data. Levels of myofibroblastic stroma varied from 0-46%, with a median of 15.1% and a standard deviation of 7.5. The myofibroblastic stromal reaction was statistically greater in grade 2 and 3 tumors (p = 0.029). Furthermore, there was a trend for worse progression-free survival in the group of node-negative tumors with strong smooth-muscle actin stromal expression (Log rank = 0.075). The present study demonstrates that the myofibroblastic reaction of breast invasive carcinoma of no special type is not merely a passive reaction, but seems to be an integral part of the neoplastic process by facilitating tumor progression and invasion. Additional, larger studies on mechanisms of stromal change are needed and may potentially lead to novel treatments.
| S-EPMC6428301 | biostudies-literature
Project description:Mutations in the p53 gene are amongst the most frequent aberrations seen in human cancer. Our objective was to characterize the clinical characteristics associated with p53 mutation in patients with advanced cancer.We retrospectively reviewed and analyzed the clinical features and response to standard systemic therapy of 145 patients with documented tumor p53 mutational status (mutant-type [mtp53] vs. wild-type [wtp53]) referred to the Clinical Center for Targeted Therapy.Sixty-six (45.5%) patients had mtp53. Mutations in p53 occurred more frequently in older patients (p= 0.015) and in Caucasians (p=0.024). The incidence of liver metastases was 69.2% vs. 43%, p=0.002 in mtp53 and wtp53, respectively. PTEN loss by immunohistochemistry was found more frequently in mtp53-bearing tumors compared to wtp53 (33.3% vs. 10%, p=0.007). The best progression-free survival (PFS) on standard systemic therapy was significantly longer with bevacizumab-containing regimens as compared to non-bevacizumab containing regimen in patients with mtp53 (median 11.0 [95% CI 5.9-16.0], n=22 vs. 4.0 months [95% CI 3.6-5.7], n=35, p<0.0001) but not those with wtp53 (median 5.0 [95% CI 2.0-7.6] vs. 6.0 [95% CI 4.0-7.5] months, p=0.318. The median overall survival from diagnosis in patients with mtp53 and wtp53 was 7.4 [95% CI 6.3-9.8] vs. 11.8 [95% CI 2.9-21.5] years, respectively (p=0.365).Patients with mtp53 tumors were older at diagnosis, had more incidence of liver metastasis, and more frequent PTEN loss. The best PFS on standard systemic therapy was significantly longer with bevacizumab-containing regimens in patients with mutant p53 tumors but not in those with wtp53.
| S-EPMC3742831 | biostudies-literature
Project description:Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on overall survival (OS) when progression-free survival (PFS) was used to assess treatment effect in metastatic cancer. Their simulation studies found no statistical difference in OS because of dilution effect from SPP, although there was a statistical difference in PFS between treatment arms. Recently, two phase III clinical trials showed efficacy of experimental treatments in OS, but not PFS. These results seem counterintuitive, because it may be reasonable to consider that the effect of treatment in prolonging PFS can influence OS prolongation. We conducted simulations to examine the role of SPP in OS under the assumption that only SPP, and not PFS, differed between treatment arms. We also explored the impact of patient heterogeneity on the OS analysis. Our study offers a reasonable explanation for the two phase III trials and recommends further discussion of PFS as an adequate endpoint and what role SPP might play in OS to evaluate current treatment regimens.
| S-EPMC4609552 | biostudies-literature
Project description:Clinical scores, molecular markers and cellular phenotypes have been used to predict the clinical outcomes of patients with glioblastoma. However, their clinical use has been hampered by confounders such as patient co-morbidities, by the tumoral heterogeneity of molecular and cellular markers, and by the complexity and cost of high-throughput single-cell analysis. Here, we show that a microfluidic assay for the quantification of cell migration and proliferation can categorize patients with glioblastoma according to progression-free survival. We quantified with a composite score the ability of primary glioblastoma cells to proliferate (via the protein biomarker Ki-67) and to squeeze through microfluidic channels, mimicking aspects of the tight perivascular conduits and white-matter tracts in brain parenchyma. The assay retrospectively categorized 28 patients according to progression-free survival (short-term or long-term) with an accuracy of 86%, predicted time to recurrence and correctly categorized five additional patients on the basis of survival prospectively. RNA sequencing of the highly motile cells revealed differentially expressed genes that correlated with poor prognosis. Our findings suggest that cell-migration and proliferation levels can predict patient-specific clinical outcomes.
| S-EPMC7855796 | biostudies-literature
Project description:Many cancers adapt to chemotherapeutic agents by upregulating membrane efflux pumps that export drugs from the cytoplasm, but this response comes at an energetic cost. In breast cancer patients, expression of these pumps is low in tumors before therapy but increases after treatment. While the evolution of therapeutic resistance is virtually inevitable, proliferation of resistant clones is not, suggesting strategies of adaptive therapy. Chemoresistant cells must consume excess resources to maintain resistance mechanisms, so adaptive therapy strategies explicitly aim to maintain a stable population of therapy-sensitive cells to suppress growth of resistant phenotypes through intratumoral competition. We used computational models parameterized by in vitro experiments to illustrate the efficacy of such approaches. Here, we show that low doses of verapamil and 2-deoxyglucose, to accentuate the cost of resistance and to decrease energy production, respectively, could suppress the proliferation of drug-resistant clones in vivo. Compared with standard high-dose-density treatment, the novel treatment we developed achieved a 2-fold to 10-fold increase in time to progression in tumor models. Our findings challenge the existing flawed paradigm of maximum dose treatment, a strategy that inevitably produces drug resistance that can be avoided by the adaptive therapy strategies we describe.
| S-EPMC3525750 | biostudies-other
Project description:BACKGROUND:Meningiomas are the most common primary tumors of the central nervous system. In patients with WHO grade I meningiomas no adjuvant therapy is recommended after resection. In case of anaplastic meningiomas (WHO grade III), adjuvant fractionated radiotherapy is generally recommended, regardless of the extent of surgical resection. For atypical meningiomas (WHO grade II) optimal postoperative management has not been clearly defined yet. METHODS:We conducted a retrospective analysis of patients treated for intracranial atypical meningioma at Charité Universitätsmedizin Berlin from March 1999 to October 2018. Considering the individual circumstances (risk of recurrence, anatomical location, etc.), patients were either advised to follow a wait-and-see approach or to undergo adjuvant radiotherapy. Primary endpoint was progression-free survival (PFS). RESULTS:This analysis included 99 patients with atypical meningioma (WHO grade II). Nineteen patients received adjuvant RT after primary tumor resection (intervention group). The remaining 80 patients did not receive any further adjuvant therapy after surgical resection (control group). Median follow-up was 37?months. Median PFS after primary resection was significantly longer in the intervention group than in the control group (64?m vs. 37?m, p?=?0.009, HR?=?0.204, 95% CI?=?0.062-0.668). The influence of adjuvant RT was confirmed in multivariable analysis (p?=?0.041, HR?=?0.192, 95% CI?=?0.039-0.932). CONCLUSIONS:Our study adds to the evidence that RT can improve PFS in patients with atypical meningioma.
| S-EPMC6719347 | biostudies-literature
Project description:The prognosis of hepatocellular carcinoma (HCC) after surgery is poor due to its high recurrence rate. Oligonucleotide microarrays were used to analyze the gene expression of HCC patients with differing recurrent-free survival times following resection to see if gene expression can predict recurrence of HCC. Keywords: Disease states analysis
2009-04-24 | GSE11260 | GEO
Project description:ImportanceBased on efficacy results from pivotal randomized clinical trials, PD-1 (programmed cell death 1) inhibitors, such as nivolumab and pembrolizumab, have been approved to treat various cancers. Response patterns with varying effects on progression-free survival (PFS) and overall survival (OS) have been reported for these drugs.ObjectiveTo compare 2 outcomes for PD-1 inhibitors: the correlation between PFS and OS and the differences in treatment effect size between PFS and OS.Data sourcesA systematic search of PubMed, Google Scholar, the Cochrane Library, Web of Science, and conference abstracts for randomized clinical trials of nivolumab and pembrolizumab published in English.Study selectionRandomized clinical trials of nivolumab or pembrolizumab in adults with solid-tissue cancers with a nonimmunotherapy control.Data extraction and synthesisTwo reviewers screened the studies for selection and extracted data on medians and hazard ratios (HRs) for PFS and OS. A pooled meta-analysis was conducted.Main outcomes and measuresAcross all trials, correlation coefficients between median PFS and median OS and between PFS benefit and OS benefit as well as the HRs of PFS and OS were assessed. The difference in treatment effect sizes between PFS and OS was assessed using a ratio of HRs (rHR). Subgroup analyses were conducted to observe differences based on drug, tumor type, and timing of therapy.ResultsTen randomized clinical trials that included 4653 patients and met inclusion criteria were identified, as were 2 others (comprising 764 patients) in which nivolumab or pembrolizumab was used following treatment with ipilimumab. The correlations between median PFS and median OS (r?=?0.676; R2?=?0.457; P?=?.09) and the correlations between the change in PFS and the change in OS (r?=?0.474; R2?=?0.225; P?=?.28) were not significant. However, the correlation between HRs of PFS and OS was significant (r?=?0.637; R2?=?0.406; P?=?.048). Using random-effects meta-analysis, the protective effects of treatment were greater for OS than for PFS (pooled rHR, 1.18; 95% CI, 1.06-1.31; P?=?.002). There was no statistical evidence for heterogeneity across the studies (Q?=?6.24; P?=?.72; I2?=?0%). Subgroup analyses showed some differences in the treatment effect sizes based on drug type, tumor type, and line of therapy.Conclusions and relevanceThere was no significant correlation between OS and PFS in terms of medians and gains in medians, but their HRs were significantly correlated. The protective effects of treatment were greater for OS than for PFS. Traditional Response Evaluation Criteria in Solid Tumors-based PFS cannot capture the benefit of PD-1 inhibitors in patients with solid tumors, and OS should remain the gold standard.
| S-EPMC6324401 | biostudies-literature