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.

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.

Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer.

PURPOSE: The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). METHOD: A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end-of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. RESULTS: Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning domains and worse overall health at both time points. CONCLUSION: Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical practice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research.

Symptom burden and quality of life with chemotherapy for recurrent ovarian cancer: the Gynecologic Cancer InterGroup-Symptom Benefit Study.

OBJECTIVE: The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with ≥3 lines of chemotherapy (PPS-ROC ≥3). METHODS: Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated ≥4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of ≤3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores ≥10 points above baseline in the QLQ-C30 summary score scale (range 0-100). RESULTS: Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC ≥3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC ≥3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC ≥3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline. CONCLUSION: Over 50% of participants reported abdominal and psychological symptoms at baseline. Of those, 40% reported an improvement within 2 months of starting chemotherapy. Approximately one in six participants reported an improvement in HRQL. Symptom monitoring and supportive care is important as chemotherapy palliated less than half of symptomatic participants.

Validation of the modified Glasgow Prognostic Score (mGPS) in recurrent ovarian cancer (ROC) - Analysis of patients enrolled in the GCIG Symptom Benefit Study (SBS).

BACKGROUND: Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS). METHODS: mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS). RESULTS: Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p<0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p=0.02). Worse PS and higher mGPS were associated with poorer HRQL (p<0.001). Higher mGPS was associated with worse HRQL, independent of PS. CONCLUSION: The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification.

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.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis.

PURPOSE: The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. METHODS: This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. RESULTS: Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively. CONCLUSION: Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.