Analysis of patients undergoing surgery as part of treatment strategy. This cohort study was nested within a randomized trial of firstline chemotherapy and bevacizumab andor cetuximab for advanced or metastatic crc. We propose a working hypothesis that integrates data from the calgb swog 80405 and fire3 studies to explain apparent discrepancies in their results. A randomized phase iii trial of sequential chemotherapy using doxorubicin, paclitaxel, and cyclophosphamide or concurrent doxorubicin and cyclophosphamide followed by paclitaxel at 14 or 21 day intervals in women with node positive stage iiiiia breast cancer. First combination of biologics calgb 80405 is the only largescale us clinical trial in which avastin and erbitux are being combined as part of firstline therapy for metastatic colon cancer. This supplementary material has been provided by the authors to give readers additional information about their work. Statistical modeling of calgb 80405 alliance to identify influential factors in metastatic colorectal cancer crc dependent on primary 1o tumor side. Federico innocenti, md, phd, from the university of north carolina, chapel hill. Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer crc is less clear. Biomarkers in predicting response to cetuximab in patients. Impact of consensus molecular subtype on survival in patients with. Secondary objectives included progressionfree survival and overall response rate, sitereported.
Aug 26, 2019 calgb 80405 pdf posted on august 26, 2019 by admin asco, itt, kraswt primary os results. There was no difference in os between arms, with os 29. Calgb swog 80405 was a randomized phase iii trial of cetuximab or bevacizumab with folfiri or mfolfox6 for patients with kras wildtype untreated metastatic adenocarcinoma of the colon or rectum. Primary tumour location has emerged as an important characteristic in understanding the outcomes for patients with colorectal cancer. Progression free survival was similar between treatments. The calgb swog 80405 trial which compared antiegfr versus antivegf, both combined with chemotherapy regimens in firstline therapy of mcrc, is the only trial conducted as a headtohead analysis. Researchers at the usc norris comprehensive cancer center found that identifying a metastatic colorectal cancer patients consensus molecular subtype cms could help oncologists determine the. Bayesian machine learning on calgbswog 80405 alliance and. Effect of firstline chemotherapy combined with cetuximab or. A metaanalysis of fire3aio krk0306, calgbswog 80405 and peak study. Colorectal cancer is the second leading cause of cancer death in the u. Primary and secondary endpoints were overall and progressionfree survival. Figure 2 shows the frequency of cms groups in calgb swog 80405 overall and by tumor location.
During the special session at esmo 2014 congress madrid, spain on defining the optimal treatment strategy with antiegfr or antivegf treatments in firstline ras wild type metastatic colorectal cancer patients, the calgb swog 80405 researchers presented long awaited results of overall survival in all ras wild type population, while fire3 study researchers presented independent radiological. This cohort study used data from individuals who were enrolled in cancer and leukemia group b now part of alliance for clinical trials in oncologysouthwest oncology group 80405 calgb swog 80405, 12 a national cancer institutesponsored trial of firstline therapy for advanced or metastatic colorectal cancer, between october 27, 2005. A phase ii study of dasatinib and dexamethasone as primary. Patients with diabetes tolerate firstline treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes. The median pfs was the reported to be the same median 10.
Current and emerging biomarkers in metastatic colorectal. Calgb swog 80405 study design and post hoc analyses 810 calgb swog 80405 study design. There were 94 pts free of disease following surgery, median fu 40 mos. Calgb failed to meet its primary endpoint of os cetuximab is not superior to avastin in 1l kraswt.
Patients without reported death were censored at their last known followup. Choices of therapy for metastatic colorectal cancer. However, with the fda approval of bevacizumab for mcrc in 2004, calgb 80203 was closed and its analysis plan was formally redesigned as a 1. Does sidedness matter in unresectable colorectal cancer. Plasma 25hydroxyvitamin d levels and survival in patients. Bayesian machine learning approach was applied on these datasets to discover gender.
Survival comparable with bevacizumab, cetuximab in mcrc. For example, posthoc analyses of the calgb swog 80405 phase. The median overall survival was similar in the erbitux combination and the avastin combination groups about 29 months and so was the progression free survival in both groups about 10. Diabetes and clinical outcome in patients with metastatic. Three studies, the phase iii fire3 aio krk0306, the phase ii peak, and the recently presented phase iii calgb swog 80405 trial, have addressed this issue faceon, directly comparing the addition of bevacizumab versus cetuximab or panitumumab to folfoxfolfiri in terms of efficacy outcomes. Calgb 80405 trial results in metastatic colorectal cancer. A studylevel metaanalysis of efficacy data from headtohead first. Body mass index and weight loss in metastatic colorectal cancer. Impact of primary tumor location on overall survival and progression free survival in patients with metastatic colorectal cancer. Effect of firstline chemotherapy combined with cetuximab. The calgb 80405 phase 3 trial is the third study comparing first line cetuximab to bev in combination with ct 66. To individually model all combinations of 99 potentially.
There has never been a phase iii study that showed no progression free survival advantage that then led to a survival advantage, he said. Statistical modeling of calgb 80405 alliance identifies. In the final 80405 trial design, 17 patients with treatmentnaive kras wildtype codons 12 and mcrc performance status 01 were randomized in a 1. Cms is prognostic in calgb swog 80405 of 1,7 patients enrolled in the primary analysis cohort of calgb swog 80405, cms classi. Calgb 80405 what this study is about a cancer study that compared different chemotherapy drug treatments for adults with colon or rectal cancer that has returned or spread throughout the body. And therefore, it would be, in my clinic at least, the first choice in a metastatic patient. Primary study contributors included teams led by alan venook, md, from the university of california, san francisco. Progression free survival median progression free survival sunitinib 3. Jan 22, 2021 calgb 80405 pdf posted on january 22, 2021 asco, itt, kraswt primary os results. May 16, 2020 calgb 80405 pdf may 16, 2020 admin medical asco, itt, kraswt primary os results. Concurrently, the cooperative group then initiated calgb 80405 to evaluate bevacizumab, cetuximab, and the combination of bevacizumab and cetuximab in a randomized phase iii study. May 18, 2016 the analysis is based on the large calgb swog 80405 trial, which looked at outcomes in patients given standard chemotherapy for metastatic colon cancer with the addition of either cetuximab or.
Analysis of calgb swog 80405 alliance 1 the relationship between primary tumor sidedness and prognosis in colorectal cancer 2. Identi cation of a genomic region between and hsp90ab1. The calgb study found that the median overall survival was identical for the two biological therapies,3 whereas the fire3 study found a significant. Expanded 80405 study mutation analysis fails to resolve. Both trials assessed the combination of either cetuximab or bevacizumab with a different chemotherapy backbone. Primary 1 tumor location as an independent prognostic. Summary of treatment administration on calgb swog 80405 by agent and treatment arm. Sep 30, 2014 venook a, niedzwiecki d, lenz h, mahoney m, inncenti f, oneil b, et al.
Impact of consensus molecular subtype on survival in. Os and progressionfree survival pfs in relation to the applied treatment. Associations with bonferroniadjusted p values free upon purchase figure 1. Folfiri plus cetuximab or bevacizumab for advanced colorectal. Secondary objectives included progression free survival and overall response rate, sitereported. Nov 18, 2010 calgb swog150506 80405 braf calgb swog150506 80405 braf cdr0000688745 registry identifier. The clinical trial design of calgbswog 80405 underwent. Impact of consensus molecular subtype on survival in patients. Plasma 25hydroxyvitamin d levels and survival in patients with. Selection of biologics for patients with metastatic. Calgb swog 80405 was a randomized phase iii trial of cetuximab or bevacizumab with folfiri or mfolfox6 for patients with kras wildtype untreated metastatic adenocarcinoma of the. Results from the calgbswog 80405 and fire3 aio krk0306. A phase iii trial of irinotecan 5fu leucovorin or oxaliplatin 5fu.
Erbitux is an engineered antibody similar to those produced by the immune system to. Pdf gene expression markers of efficacy and resistance to. Identifying colorectal cancer subtypes could improve. The primary endpoints were overall survival os and progressionfreesurvival pfs. Not preplanned so could not control for r and l imbalances, e. Cetuximab or bevacizumab in metastatic colorectal cancer. The secondary endpoint of progression free survival pfs was calculated from study entry.
Sw rochester mn 55905 alliance patient registration tel. The folfiri group in calgb 80405 showed confl icting results, with a nonsignifi cant improvement in overall survival in favour of the addition of bevacizumab over cetuximab 334 months vs 289 months. Impact of primary 1 tumor location on overall survival os and progression free survival pfs in patients pts with metastatic colorectal cancer mcrc. Association of diet quality with survival among people with. Patients were enrolled at 508 community and academic. Group b calgb 80405 trial showed that, in treatment naive patients with mcrc.
But until now, it was unclear which drugs were most effective for which patients. This is the calgb swog 80405 trial reference corresponding to an oral presentation at the european society of medical oncology congress on 2014. Diabetes and clinical outcome in patients with metastatic colorectal cancer. The data align well with the retrospective analyses of the phase 3 randomized calgbswog 80405 and fire3 trials conducted in the united. Calgb 80405 s primary endpoint was overall survival, venook noted, as opposed to fire 3, which had investigatoradjudicated response rate as the primary endpoint. Calgb cancer and leukemia group b now alliance for clinical trials in oncology. Calgb swog 80405 is sponsored by the national cancer institute. In calgb 80405 patients were randomized to receive standard chemotherapy with either bevacizumab which targets vascular endothelial growth factor or cetuximab in the first. A voluntary questionnaire administered within 4 weeks after initiating chemotherapy for metastatic disease was used to collect data on weight change over the prior 6 months, asking patients their weight at time of questionnaire completion. Calgbswog 80405 study16 has not been published yet, but updated. Body mass index and weight loss in metastatic colorectal. Bayesian machine learning on calgbswog 80405 alliance. The relevance of primary tumour location in patients with metastatic. Apr 29, 2020 the cancer trials support unit ctsu is a service of the national cancer institute nci designed to facilitate access to ncifunded clinical trials for qualified clinical sites and to support the management and conduct of those clinical trials.
For this analysis, they used a nanostring platform to determine the consensus molecular. The relevance of primary tumour location in patients with. Alliance calgb swog 80405 is a phase iii clinical trial w randomly assigned cetuximab cet bevacizumab bev whereas peak is a phase ii clinical trial w randomly assigned panitumumab pan bev. Venook, md, discusses findings from the phase iii calgb swog 80405 trial that compared frontline therapy with bevacizumab or cetuxim. Calgb swog 80405 study1 referred to throughout as the calgb study and the fire3 study,2 were done to clarify this question. As reported at asco in 2014, calgb 80405 did not identify any significant pfs or os differences between the bevacizumab and cetuximab cohorts in ras wt. Even though colon cancer localized to the bowel is potentially curable with surgery and adjuvant chemotherapy, advanced colon cancer is often incurable. Progressionfree a and overall b survival in the ras wildtype population n 400. Although calgb swog 80405 alliance was conducted within the nctn, which is.
Impact of primary tumor location on overall survival and. The relationship between primary tumor sidedness and prognosis in colorectal cancer 2. May 01, 2019 in conclusion, proper interpretation of the calgb swog 80405 and fire3 results requires an indepth examination of the complex interplay, not only between the targeted biological agents and chemotherapeutic drugs, but also between therapies and the tumour biology and microenvironment, for each line of treatment. The calgb swog 80405 trial which compared antiegfr versus antivegf, both combined with chemotherapy regimens in firstline therapy of mcrc, is the only trial conducted as. Impact of consensus molecular subtyping cms on overall survival os and progression free survival pfs in patients pts with metastatic colorectal cancer mcrc.
The primary endpoint of calgb swog 80405 alliance and this companion study was overall survival os. Secondary endpoints were progression free survival pfs and treatmentrelated adverse events. Furchtogott l, swanson d, hayete b, khalil, i, wuest d, rich k, nixon ab, niedzwiecki d, meyerhardt ja, oreilly em, ou f, heinz josef l, innocenti f, venook ap. A phase iii trial of 6 versus 12 treatments of adjuvant folfox plus celecoxib or placebo for patients with resected stage iii colon cancer fast facts ctc v4. Impact of consensus molecular subtyping cms on overall. The phase 3 calgb swog 80405 clinical trial compared the efficacy and safety of adding cetuximab or bevacizumab to firstline chemotherapy with either folfox or folfiri in 17 patients with kras wildtype codons 12 and mcrc lenz h, et al. Phase iii trial of irinotecan5fuleucovorin folfiri or oxaliplatin5fuleucovorin mfolfox6 with bevacizumab bv or cetuximab. Apr 28, 2019 calgb 80405 pdf april 28, 2019 admin asco, itt, kraswt primary os results. The cancer and leukemia b and southwest oncology group 80405 trial was designed in.
Firstline treatment of metastatic colorectal cancer. Although the final analysis cohort for the treatment trial was composed of only the 1,1 kras wildtype patients randomized to the bevacizumabchemotherapy arm or the cetuximabchemotherapy arm, the study population for this vitamin d study was drawn from all three arms of calgb swog 80405 alliance. Summary of major scientific amendments to calgb swog 80405. Apr 09, 2018 the other reason for that is it was seen consistently on 2 studies maverick and the little cohort of patients who went on calgb 80405 that folfiribevacizumab may have an edge over folfoxbevacizumab, directly or indirectly compared. Gi highlights from asco 2014 colorectal cancer 80405. Researchers conducted the calgb 80405 study, a randomized phase 3 trial that demonstrated no differences in overall survival os or progression free survival pfs in patients with metastatic colorectal cancer mcrc treated with bevacizumab bv or cetuximab cet as first line therapy. Dec 02, 2016 we conducted a phase ii trial at 17 u. Staging handbook 7th ed recist na although they will not be considered formal eligibility exclusion criteria, physicians should recognize. Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic crc.
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