The validity of progression‐free survival 2 as a surrogate trial end point for overall survival

Cancer ◽  
2022 ◽  
Author(s):  
Rachel G. Woodford ◽  
Deborah D.‐X. Zhou ◽  
Peey‐Sei Kok ◽  
Sally J. Lord ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
End Point

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

The effect of statins on overall survival and progression-free survival in veterans with prostate cancer: A retrospective single-center experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 169-169
Author(s):  
Brian Warnecke ◽  
Raissa Lakene Djoufack Djoumessi ◽  
Juan Garza ◽  
Michael Mader ◽  
Shreya Chaudhary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
The United States ◽  
Inverse Association ◽  
Free Survival ◽  
End Point ◽  
Anti Cancer ◽  
Statin Use

169 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often related to other medical conditions and not prostate cancer itself. Hence, it is important to optimize other co-morbidities, such as hyperlipidemia, hypertension, and cardiovascular diseases in these patients. However, there are numerous studies portraying the ability of statins to increase progression free survival and overall survival of prostate cancer. This has led to significant interest of statins having anti-cancer properties and ultimately improving long term outcomes. Methods: This is a retrospective observational study with chart review of 1,011 patients diagnosed with prostate cancer from 1995 to 2010 in a VA Hospital in San Antonio, Texas. Variables included age at diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (4 dosage levels), length of statin use, time followed in months (from diagnosis to death or end of study period), death, cause of death, and time to first progressive disease. Progressive disease was defined using PSWG2 guidelines which is PSA increase > / = 25% and at least 2ng/dl above the nadir. The Cox proportional hazards regression model was used to estimate the hazard function, with age, co-morbities and other cancers used as a covariate. End points were death by prostate cancer (56), death by any cancer (140), and death by all causes (484). We also looked at the effects of statins on progression free survival of prostate cancer. Results: The hazard ratio (HR) for use of statins and death by prostate cancer was 0.35, 95% confidence interval (CI): 0.20-0.62 (p = 0.0003), indicating that statin use has a statistically significant positive effect at delaying death by prostate cancer. Death by any cancer was significantly affected by statins with a HR of 0.47, 95% CI: 0.32-0.65 (p < 0.0001). Death by all causes was also affected significantly by statins with a HR of 0.64, 95% CI: 0.53-0.78 (p < 0.0001). Length of statin use, shorter versus longer than 4 years, showed an inverse association with our primary end point with a HR of 0.53, 95% CI: 0.40-0.69 (p < 0.0001). Dose level of statin, fourth level vs 1, 2, and 3, also showed an inverse association with our primary end point with a HR of 0.73, 95% CI: 0.57-0.94 (p = 0.014). Lastly, statin exposure significantly increased progression-free survival with a HR of 0.71, 95% CI: 0.53-0.95 (p < 0.021). Conclusions: It is clear that concomitant statin use increases overall survival in patients with prostate cancer, potentially even having anti-cancer protective effects against mortality. Longer duration of statin use and higher dose levels of statins increase length of overall survival in patients with prostate cancer. As mortality is often not due to prostate cancer, more interestingly, statin exposure is also shown to increase progression-free survival.

scholarly journals Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

2015 ◽  
Vol 33 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Qian Shi ◽  
Aimery de Gramont ◽  
Axel Grothey ◽  
John Zalcberg ◽  
Benoist Chibaudel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Individual Patient Data ◽  
Progression Free Survival ◽  
Patient Data ◽  
Biologic Agents ◽  
First Line ◽  
Free Survival ◽  
End Point

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

2019 ◽  
Vol 29 (7) ◽  
pp. 1141-1147 ◽  
Author(s):  
Domenica Lorusso ◽  
Felix Hilpert ◽  
Antonio González Martin ◽  
Joern Rau ◽  
Petronella Ottevanger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Patient Reported Outcomes ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Free Survival ◽  
End Point ◽  
Platinum Resistant ◽  
Patient Reported ◽  
Epidermal Growth

IntroductionThe PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes.Patients and methodsEligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression.ResultsAt database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms.DiscussionConsistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes.ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878.

scholarly journals Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial

2019 ◽  
Vol 37 (11) ◽  
pp. 867-875 ◽  
Author(s):  
Celeste Lebbé ◽  
Nicolas Meyer ◽  
Laurent Mortier ◽  
Ivan Marquez-Rodas ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
End Point ◽  
Phase Iiib ◽  
Grade 3

PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

scholarly journals Assessment of Progression-Free Survival as a Surrogate End Point of Overall Survival in First-Line Treatment of Ovarian Cancer

2020 ◽  
Vol 3 (1) ◽  
pp. e1918939 ◽  
Author(s):  
Xavier Paoletti ◽  
Liz-Anne Lewsley ◽  
Gennaro Daniele ◽  
Adrian Cook ◽  
Nozomu Yanaihara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
End Point ◽  
First Line Treatment

scholarly journals Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study

2021 ◽  
pp. JCO.21.00396
Author(s):  
Shaodong Hong ◽  
Yaxiong Zhang ◽  
Gengsheng Yu ◽  
Peijian Peng ◽  
Jiewen Peng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
End Point ◽  
Metastatic Nasopharyngeal Carcinoma ◽  
Phase Iii Study

PURPOSE GEM20110714 (ClinicalTrials.gov identifier: NCT01528618 ), the first randomized, phase III study of systemic chemotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC), reported significant progression-free survival improvement with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio, 0.55; 95% CI, 0.44 to 0.68; P < .001). Data from the final analysis of overall survival (OS) are presented here. METHODS From February 2012 to October 2015, 362 patients were randomly assigned to receive either GP (gemcitabine 1 g/m2 once daily on days 1 and 8 and cisplatin 80 mg/m2 once daily on day 1; n = 181) or FP (fluorouracil 4 g/m2 in continuous intravenous infusion over 96 hours and cisplatin 80 mg/m2 once daily on day 1; n = 181) once every 21 days. The primary end point was progression-free survival, which has been previously reported; OS was a secondary end point. RESULTS After a median follow-up time of 69.5 months with GP and 69.7 months with FP, 148 (81.8%) and 166 (91.7%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.72 (95% CI, 0.58 to 0.90; two-sided P = .004). The median OS was 22.1 months (95% CI, 19.2 to 25.0 months) with GP versus 18.6 months (95% CI, 15.4 to 21.7 months) with FP. The OS probabilities at 1, 3, and 5 years were 79.9% versus 71.8%, 31.0% versus 20.4%, and 19.2% versus 7.8%, respectively. Poststudy therapy was administered in 51.9% and 55.2% of patients in the GP and FP arms, respectively. CONCLUSION Among patients with previously untreated advanced nasopharyngeal carcinoma, those who receive GP have longer OS than those receive FP. Gemcitabine plus cisplatin should be considered a preferred front-line option for these patients.

scholarly journals Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma

2017 ◽  
Vol 6 (12) ◽  
pp. 2766-2774 ◽  
Author(s):  
Ana Jiménez-Ubieto ◽  
Carlos Grande ◽  
Dolores Caballero ◽  
Lucrecia Yáñez ◽  
Silvana Novelli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Autologous Transplant ◽  
End Point

Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

2018 ◽  
Vol 36 (8) ◽  
pp. 728-734 ◽  
Author(s):  
David S. Siegel ◽  
Meletios A. Dimopoulos ◽  
Heinz Ludwig ◽  
Thierry Facon ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Rank Test ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Risk Of Death ◽  
End Point ◽  
Grade 3

Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.

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