These bullet points are followed by a more detailed commentary. Need for survival analysis investigators frequently must analyze data before all patients have died. The survival function gives the probability that a subject will survive past time t. To investigate whether progression free survival pfs can be considered a surrogate endpoint for overall survival os in advanced nonsmallcell lung cancer nsclc. Eisenhauer, ncic clinical trials group, queens university, kingston, ontario, canada see accompanying articles on pages 1114 and 1122 the last few years have seen an increase in the number of ran. Km is a univariate approach, while cox analysis is multivariable. Tips and techniques when using proc lifetest and proc. In oncology, pfs usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiol. Pdf bias in progressionfree survival analysis due to.
The kaplanmeier estimates the probability of an event occurring at specified points in time and can. Pfs is defined as the time from randomization or start of study treatment until. Pdf prediction of survival benefits from progression. Setting five randomised controlled trials comparing docetaxelbased chemotherapy with vinorelbinebased chemotherapy for the firstline treatment.
Progression free survival pfs is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors for both practical and clinical considerations. Nov 14, 2018 here, we aimed to assess the surrogacy of progression. Differences in overall vs progressionfree survival. The relationship between pfs and os has not been well studied in later lines of treatment. Probability density functions, cumulative distribution functions and the hazard function are central to the analytic techniques presented in this paper.
Jun 17, 2016 since progression free survival is a proven surrogate endpoint for overall survival, and the median for either progression free survival or overall survival might not consistently reflect the longterm benefit of a drug, the landmark progression free survival analysis at 1 year, 2 years, and 3 years should be consistently reported endpoints in. Population analysis of tumor growth inhibition and. Progressionfree survival, postprogression survival, and. We examined whether progressionfree survival pfs, post progression survival pps, and tumor response could be valid surrogate endpoints for os after firstline chemotherapies for patients with extensive sclc using individuallevel data. Progression free survival pfs analysis in solid tumor clinical studies na li, na li clinical programming services abstract progression free survival pfs is commonly used as a primary endpoint in phase iii of solid tumor oncology clinical studies. Definition of progressionfree survival nci dictionary.
Progressionfree survival is a desirable outcome because it is not. Progressionfree survival as a surrogate end point for. Pdf progressionfree survival and time to progression as primary. Extended 4year followup and analysis of relative progression free survival. The protective effects of treatment were greater for overall survival than for progression free. Progressionfree survival pfs analysis in solid tumor clinical studies. We established the surrogate endpoints for aggressive. Mar 01, 2018 our objective was to evaluate minimal residual disease mrd at the end of induction treatment with chemoimmunotherapy as a surrogate end point for progression free survival pfs in chronic lymphocytic leukemia cll based on 3 randomized, phase 3 clinical trials clinicaltrials. Progressionfree survival pfs, timeto progression ttp and overall survival os are commonly used endpoints in. We abstracted data on progressionfree survival pfs, time to tumor.
Targeted arms that did not use a biomarker had median response rates comparable with those. Disease free survival endpoint is death or relapse is often another good choice. This is a brief introduction to survival analysis using stata. Use of progression free survival is also biased because followup on progression is often discontinued after a patient is taken off the study. Mercks keytruda pembrolizumab in combination with chemotherapy significantly improved progressionfree survival compared to chemotherapy alone as firstline treatment for extensive stage small cell lung cancer. Survival analysis methods applicable to variety of timetoevent data censoring necessitates special methods kaplanmeier summarizes survival data logrank test statistically compares survival between categorical groups next month regression analysis of survival data allowing evaluation of multiple. This is no longer necessary as we now support partsa models as a new model type. Comparison of progression free survival pfs on comprehensive mul9pla.
Nomograms predicting progressionfree survival, overall. Comparison of progressionfree survival pfs on comprehensive mul9pla. Agenda survival analysis concepts descriptive approach 1st case study which types of customers lapse early predicting survival times. May 15, 20 progression free survival pfs is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. In oncology, pfs usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Request pdf nomograms predicting progressionfree survival, overall survival, and pelvic recurrence in locally advanced cervical cancer developed from an analysis. Prediction of survival benefits from progressionfree. Metaanalysis of the association between progressionfree. For more information, go to the partitioned survival analysis page on our website. To assess the progressionfree survival pfs associated with brentuximab vedotin administered in combination with rchop or rchp, and in. The response is often referred to as a failure time, survival time, or event time. Progressionfree survival pfs is increasingly used as an important and even a primary endpoint in randomized cancer clinical trials in the evaluation of patients with solid tumors, because of both practical and clinical considerations. Schematic of potential progressionfree survival pfs and overall survival os results in trial of arm 1 experimental versus arm 2 standard. Progression, treatment failure, progression free survival, response introduction to create these oncologic efficacy summary tables use the sas procedures proc lifetest and proc phreg.
Although in its simplest form, pfs is the time from randomization to a predefined endpoint, there are many factors that can influence. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the nih. Here, we aimed to assess the surrogacy of progression. Although in its simplest form pfs is the time from. Jul 24, 2016 this video demonstrates how to perform a kaplanmeier procedure survival analysis in spss. Survival analysis is used to analyze data in which the time until the event is of interest. Survival data analysis is traditionally focused on analyzing lifetimes by using time that is measured to an event of interest. Meta analysis of individual patient data from randomised trials. Some commonly created efficacy outputs used for these analyses are. Appendix 1 to the guideline on the evaluation of anticancer. Nov 12, 2011 the validity of progression free survival pfs as a surrogate endpoint for overall survival os in metastatic colorectal cancer mcrc trials has been studied, primarily in firstline treatment. Since progression free survival is a proven surrogate endpoint for overall survival, and the median for either progression free survival or overall survival might not consistently reflect the longterm benefit of a drug, the landmark progression free survival analysis at 1 year, 2 years, and 3 years should be consistently reported endpoints in. The use of progression free survival pfs or disease free survival dfs as endpoint in clinical. Lately there is a growing interest in progression free survival pfs in studies of diseases that are slow growing and dif.
Pdf prediction of survival benefits from progressionfree. The validity of progression free survival pfs as a surrogate endpoint for overall survival os in metastatic colorectal cancer mcrc trials has been studied, primarily in firstline treatment. Since progression free survival is a proven surrogate endpoint for overall survival, and the median for either progression free survival or overall survival might not consistently reflect the longterm benefit of a drug, the landmark progression free survival analysis. Jan 31, 2014 need for survival analysis investigators frequently must analyze data before all patients have died. Bolero2 is a phase 3, doubleblind, randomized, international trial comparing everolimus 10. A model for predicting effect of treatment on progression. Progression free survival as a surrogate endpoint foroverall survival in glioblastoma. Progressionfree survival has some advantages, as an endpoint, in preference to the endpoint of overall survival. Objectives to investigate whether progression free survival pfs can be considered a surrogate endpoint for overall survival os in advanced nonsmallcell lung cancer nsclc. In an exploratory secondary analysis, the investigators found that lack of progression was independently associated with improved symptom control and qol.
Lapatinib tmtykerb is a potent and selective inhibitor of the egfr. In a clinical trial, measuring the progression free survival is one way to see how well a new treatment works. Findings the meta analysis of 346 phase 1 trial including 203 patients found that using a biomarkerbased selection strategy was associated with improved response rate median, 30. Since progression free survival is a proven surrogate endpoint for overall survival, and the median for either progression free survival or overall survival might not consistently reflect the longterm benefit of a drug, the landmark progression free survival analysis at 1 year, 2 years, and 3 years. An introduction to survival analysis using complex.
Jan 22, 2007 with the advent of ever more effective second and third line cancer treatments and the growing use of crossover trial designs in oncology, in which patients switch to the alternate randomized treatment upon disease progression, progression. Population analysis of tumor growth inhibition and progression free survival following lapatinib treatment in patients with advancedmetastatic breast cancer jianping zhang, kevin koch. Important distributions in survival analysis understanding the mechanics behind survival analysis is aided by facility with the distributions used, which can be derived from the probability density function and cumulative density functions of survival times. Progression free survival is the length of time during and after treatment in which a. Survival analysis gives patients credit for how long they have been in the study, even if the outcome has not yet occurred. Findings this meta analysis of 12 randomized clinical trials found no significant correlation between overall survival and progression free survival in terms of medians and gains in medians, but their hazard ratios were significantly correlated. Findings from the analysis and research in cancers of the digestive system database. With the advent of ever more effective second and third line cancer treatments and the growing use of crossover trial designs in oncology, in which patients switch to the alternate randomized treatment upon disease progression, progression.
Progressionfree survival pfs, timetoprogression ttp and overall survival os are commonly used endpoints in. Starting stata doubleclick the stata icon on the desktop if there is one or select stata from the start menu. Individual patient data analysis of progression free survival versus overall survival as a firstline end point for metastatic colorectal cancer in modern randomized trials. Progressionfree survival as a surrogate endpoint for.
There are many stata commands for input, management, and analysis of survival data, most of which are found in the manual in the st section all survival data commands start with st. Progressionfree survival pfs is an increasingly important endpoint in cancer drug devel opment. Everolimus plus exemestane in postmenopausal patients with. This video demonstrates how to perform a kaplanmeier procedure survival analysis in spss. An introduction to survival analysis dr barry leventhal transforming data henry stewart briefing on marketing analytics 19th november 2010. Progression free survival pfs is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. One such end point, radiographic progression free survival rpfs, is not affected by postprotocol treatments, but it has been difficult to quantify because of the lack of standardization of the outcome measure itself. Mrk, known as msd outside the united states and canada, today announced that the phase 3 keynote204 trial evaluating keytruda, mercks antipd1 therapy, for the treatment of adult patients with relapsed or refractory classical hodgkin lymphoma chl met one of its dual primary endpoints of progression free survival pfs. Progression free survival has some advantages, as an endpoint, in preference to the endpoint of overall survival. Progressionfree survival as a surrogate endpoint for overall. Issues in using progressionfree survival when evaluating.
To assess the progressionfree survival pfs associated with brentuximab vedotin. Role of sensitivity analyses in assessing progressionfree. Progressionfreesurvival pfs analysis in solid tumor. Confusion from effects of nonstudy drugs given to subjects who leave the trial collecting data on overall survival may require an extended followup period. Minimum followup of 11 months1,8 at 5 years, opdivo increased os in squamous mnsclc9 checkmate 057. Similarly, disease free survival is when patients have had. Recommendations for the assessment of progression in. Progression free survival an overview sciencedirect topics. Progression free survival is the length of time during and after treatment in which a patient is living with a disease that does not get worse.
Everolimus plus exemestane in postmenopausal patients. Progression free survival pfs is an important endpoint used in many phase ii designs. Progression free survival may be used in a clinical study or trial to help find out how well a new treatment works. Setting five randomised controlled trials comparing docetaxelbased chemotherapy with vinorelbinebased. This project was supported by the national center for advancing translational sciences, national institutes of health, through ucsfctsi grant number ul1 tr000004.
Survival analysis survival data characteristics goals of survival analysis statistical quantities survival function. Sample size survival analysis sample size calculators. In summary, criteria for progression should include the. The use of progressionfree survival pfs or diseasefree survival dfs. This updated analysis was conducted to characterize overall survival os and update pfs outcomes. In summary, as the above data shows, this patient has progression disease pd on. Decide on output file type pdf, html, rtfdecide on output file type pdf, html, rtf ods pdf fileex1. The pcwg2 sought to establish a definition for rpfs that would ensure that a drug was not working before therapy was discontinued. Progressionfree survival wikimili, the free encyclopedia. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival os or progression free survival pfs. A brief introduction to survival analysis using stata. Publications home of jama and the specialty journals of the. Partitioned survival analysis partsa has been used often in the context of evaluating oncology treatments. Kaplanmeier procedure survival analysis in spss youtube.
In many clinical settings, changes in pfs with the introduction of a new treatment may represent true benefit in terms of the gold standard outcome, overall survival os. Modeling the relationship between progressionfree survival. Chapter 2 kaplanmeier survival curves and the logrank test. Disease free survival after bone marrow transplant time to death or disease progression. Progressionfree survival pfs is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. Progression free survival pfs has been adopted as the primary endpoint in. Source of investigation were the protocols of cancer clinical trials included in the italian registry of clinical trials from 2000 to 2005. Table 2 calculation of the relapsefree survival probability for patients in the. Nov 21, 2017 determination of an optimal response cutoff able to predict progression free survival in patients with welldifferentiated advanced pancreatic neuroendocrine tumours treated with sunitinib. Creating a partitioned survival analysis model in treeagepro. Partsa models differ from state progression models in an important way.
In the primary analysis of this phase ii study, combination cediranibolaparib improved progression free survival pfs compared with olaparib alone in relapsed platinumsensitive ovarian cancer. Overall survival and updated progressionfree survival. Bias in progressionfree survival analysis due to intermittent assessment of progression article pdf available in statistics in medicine 3424 may 2015 with 74 reads how we measure reads. Bolero2 is a phase 3, doubleblind, randomized, international trial comparing everolimus 10 mgday plus exemestane.
In recent years, there has been considerable progress in the treatment of chronic lymphocytic leukemia cll, with median progression free survival pfs now approaching 5 years in firstline cll studies. An introduction to survival analysis barryanalytics. Design meta analysis of individual patient data from randomised trials. Cumulative hazard function onesample summaries kaplanmeier estimator. When evaluating interventions in oncology patients, a frequently used outcome measure is progression free survival pfs, defined to be the time to the detection of progressive disease or to the patients death. Survival analysis part i netherlands cancer institute. Radiographic progressionfree survival as a clinically. For statistical details, please refer to the sasstat introduction to survival analysis procedures or a general text on survival analysis hosmer et al. Progression free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials. Median progressionfree survival was 124 months 95% ci 1045 in the placebo group versus 187 months 166216 in the pertuzumab group, which accords with results at the primary analysis.
408 1230 405 1619 804 63 496 422 1040 745 1003 433 151 474 550 1578 945 416 409 1311 54 863 1600 597 1493 844 1227 1134 855 1277 485 951 660 122 558