Progression-free survival, patient-reported outcomes, and the Holy Grail

2014 ◽  
Vol 12 (8) ◽  
pp. 265-266 ◽  
Author(s):  
David Cella
Keyword(s):  
Patient Reported Outcomes ◽  
Progression Free Survival ◽  
Holy Grail ◽  
Free Survival ◽  
Patient Reported

scholarly journals Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial

2019 ◽  
Vol 37 (32) ◽  
pp. 2968-2973 ◽  
Author(s):  
Josep M. del Campo ◽  
Ursula A. Matulonis ◽  
Susanne Malander ◽  
Diane Provencher ◽  
Sven Mahner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Partial Response ◽  
Maintenance Therapy ◽  
Clinical Benefit ◽  
Patient Reported Outcomes ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Patient Reported

PURPOSE In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274 ), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy. PATIENTS AND METHODS A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (g BRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed g BRCAmut (non–g BRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to g BRCAmut status and response to their last platinum-based therapy. Ovarian cancer–specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy–Ovarian Symptom Index. RESULTS Progression-free survival was improved in patients treated with niraparib compared with placebo in both the g BRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non–g BRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes. CONCLUSION Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.

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 Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair–Deficient/Microsatellite Instability–High Metastatic Colorectal Cancer

2018 ◽  
Vol 36 (8) ◽  
pp. 773-779 ◽  
Author(s):  
Michael J. Overman ◽  
Sara Lonardi ◽  
Ka Yeung Mark Wong ◽  
Heinz-Josef Lenz ◽  
Fabio Gelsomino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Clinical Benefit ◽  
Patient Reported Outcomes ◽  
Progression Free Survival ◽  
Free Survival ◽  
Dna Mismatch ◽  
Patient Reported

Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti–programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.

Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity andKRASstatus in patients receiving panitumumab monotherapy

Cancer ◽  
2009 ◽  
Vol 115 (7) ◽  
pp. 1544-1554 ◽  
Author(s):  
Marc Peeters ◽  
Salvatore Siena ◽  
Eric Van Cutsem ◽  
Alberto Sobrero ◽  
Alain Hendlisz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Reported Outcomes ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Free Survival ◽  
Patient Reported

scholarly journals Patient-reported outcomes in clinical trials

2016 ◽  
Vol 4 (2) ◽  
pp. 54-58
Author(s):  
Florence Joly ◽  
Gloria Mittica
Keyword(s):  
Clinical Trials ◽  
Health Care Professionals ◽  
Patient Reported Outcomes ◽  
Specific Treatment ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Treatment Benefit ◽  
Free Survival ◽  
Disease Response ◽  
Patient Reported

Patient-reported outcomes (PROs) are progressively being included in clinical trials to provide information about treatment benefits identified by the patients themselves that extend the data on traditional clinical trial endpoints, such as disease free survival, overall survival, progression-free survival, and response rate. PROs may have a greater impact for patients than other endpoints. For example, patients may be prepared to forgo some increase in progression-free survival in return for reduced treatment-related toxicity. PROs may also be an indicator of disease response and have value as prognostic factors. This article discusses the way PROs can be defined and incorporated into clinical trials to enhance the value of clinical trials data and improve the understanding of the clinical benefits of a specific treatment, not only for health care professionals, but for patients and caregivers. The importance and relevance of a patient-centered perspective and shared decision making in defining value and determining treatment benefit is increasingly recognized. However, despite the acknowledged value of PROs, their inclusion in clinical trials remains far from ideal. New guidelines from the research community and technological improvements in data collection and analytics will increase the quality and the importance of PROs as standard methods for the evaluation of medical studies and in the drugs approval process.

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

scholarly journals Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

2019 ◽  
Vol 37 (29) ◽  
pp. 2661-2669 ◽  
Author(s):  
Bhishamjit S. Chera ◽  
Robert J. Amdur ◽  
Rebecca Green ◽  
Colette Shen ◽  
Gaorav Gupta ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Patient Reported Outcomes ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Post Treatment ◽  
Free Survival ◽  
Patient Reported

PURPOSE To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events). RESULTS One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events. CONCLUSION Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

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