Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(> 3) chemotherapy – the GCIG Symptom Benefit Study (SBS)

Background: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. Methods: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. Results: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0–1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7–7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. Conclusion: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3

Patient-Reported Outcomes in Ovarian Cancer: Facilitating and Enhancing the Reporting of Symptoms, Adverse Events, and Subjective Benefit of Treatment in Clinical Trials and Clinical Practice

Rachel Campbell,1 Madeleine T King,1 Martin R Stockler,2 Yeh Chen Lee,2– 4 Felicia T Roncolato,2,5 Michael L Friedlander3,4 1University of Sydney, Faculty of Science, School of Psychology, Sydney, NSW, Australia; 2University of Sydney, NHMRC Clinical Trials Centre, Sydney, NSW, Australia; 3School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Prince of Wales and Royal Hospital for Women, Sydney, NSW, Australia; 5MacArthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, NSW, AustraliaCorrespondence: Rachel Campbell, University of Sydney, Room 325, Brennan-Maccallum Building, Sydney, NSW, 2006, Australia, Tel +61 2 8627 7631, Email [email protected]: Patient-reported outcomes (PROs) provide a valid, standardized way of assessing symptoms, adverse events and the subjective benefit of treatment from the patient’s perspective. Assessment of PROs is critical in ovarian cancer due to the high morbidity of the disease and its treatments. Several well-validated PRO measures are available to assess PROs in ovarian cancer. Their inclusion in clinical trials can provide evidence on the benefits and harms of new treatments based on patients’ experiences to guide improvements in clinical practice and health policy. Aggregate PRO data collected in clinical trials can be used to inform patients about likely treatment impacts and assist them to make informed treatment decisions. In clinical practice, PRO assessments can facilitate monitoring of a patient’s symptoms throughout treatment and follow-up to guide their clinical management; in this context, an individual patient’s responses can facilitate communication with their treating clinician about troublesome symptoms and their impact on their quality of life. This literature review aimed to provide clinicians and researchers with a better understanding of why and how PROs can be incorporated into ovarian cancer clinical trials and routine clinical practice. We discuss the importance of assessing PROs throughout the ovarian cancer disease and treatment trajectory in both clinical trials and clinical practice, and provide examples from existing literature to illustrate the uses of PROs as the goals of treatment change in each setting.Keywords: ovarian cancer, patient-reported outcomes, clinical trials, clinical practic

Quality of life predicts overall survival in women with platinum-resistant ovarian cancer: an AURELIA substudy

BackgroundWomen with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months. We hypothesized that their quality of life (QoL) scores would be prognostic.Patients and methodsData from AURELIA (n = 326), a randomized trial of chemotherapy with or without bevacizumab, were used to identify baseline QoL domains [EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 and OV28] that were significantly associated with overall survival in multivariable Cox regression analyses. Patients were classified as having good, medium, or poor risk. Cutpoints were validated in an independent dataset, CARTAXHY (n = 136). Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors. The additional QoL information was assessed using C statistic.ResultsIn AURELIA, all domains, except cognitive function, predicted overall survival in univariable analyses. Physical function (P &lt; 0.001) and abdominal/gastrointestinal symptom (P &lt; 0.001) scores remained significant in multivariable models. In high (score &lt;67), medium (67-93), and low (&gt;93) risk categories for physical function, median overall survival was 11.0, 14.7, and 19.3 months, respectively (P &lt; 0.001). In CARTAXHY, median overall survival was 7.9, 16.2, and 23.9 months (P &lt; 0.001), respectively. For high- (&gt;44), medium- (13-44), and low- (&lt;13) risk categories for abdominal/gastrointestinal symptoms, median overall survival was 11.9, 14.3, and 19.7 months in AURELIA (P &lt; 0.001) and 10.5, 19.6, and 24.1 months in CARTAXHY (P = 0.02). Physical function (P = 0.02) and abdominal/gastrointestinal symptoms (P = 0.03) remained independent prognostic factors after adjustment for clinicopathological factors. The C statistic of the full model was 0.71. For QoL factors alone, patient factors alone and disease factors alone, the C statistics were 0.61, 0.61, and 0.67 respectively.ConclusionsPhysical function and abdominal/gastrointestinal symptom scores improved predictions of overall survival over clinicopathological factors alone in platinum-resistant ovarian cancer. This additional prognostic information could improve trial stratification, patient-doctor communication about prognosis, and clinical decision-making.Clinical trial registrationNCT00976911

Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer-The GCIG Symptom Benefit Study

Background. Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health‐related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. / Materials and Methods. This study enrolled women with PRROC before starting palliative chemotherapy. Health‐related quality of life was measured with EORTC QLQ‐C30/QLQ‐OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression‐free and OS. / Results. Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all p < .007); low PF and RF remained significant after adjusting for clinicopathological factors (both p < .0401). Most who stopped chemotherapy early had Eastern Cooperative Oncology Group Performance Score 0–1 at baseline (79%); PF, RF, and GHS remained independently significant predictors of stopping chemotherapy early in this subgroup. Death within 30 days of chemotherapy occurred in 14%. Low GHS, RF, and PF remained significantly associated with death within 30 days of chemotherapy after adjusting for clinicopathological factors (all p < .012). / Conclusion. Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self‐ratings of GHS, RF, and PF could improve patient‐clinician communication regarding prognosis and help decision‐making in women considering chemotherapy for PRROC. / Implications for Practice. Measuring aspects of health‐related quality of life when considering further chemotherapy in platinum resistant/refractory ovarian cancer (PRROC) could help identify women with a particularly poor prognosis who are unlikely to benefit from chemotherapy and could therefore be spared unnecessary treatment and toxicity in their last months of life. Self‐ratings of global health status, role function, and physical function could improve patient‐clinician communication regarding prognosis and help decision‐making in women considering chemotherapy for PRROC