Symptom burden and outcomes in patients with platinum resistant/refractory (PRR) and potentially platinum sensitive ROC receiving ≥3 lines of chemotherapy (PPS ≥3) – The Gynecologic Cancer Intergroup (GCIG) Symptom Benefit Study (SBS)

Background:

The primary endpoint in this clinical trial is progression free survival (PFS) which ranges between 3 – 4 months. The secondary endpoints are health related quality of life and adverse events. The proportion of patients who experience symptom benefit from treatment is not known. Adverse event reporting is by clinicians not patients. The primary objective of the GCIG Symptom Benefit Study is to validate the MOST (Measure of Ovarian Cancer Symptoms and Treatment concerns) which was developed to measure symptom benefit in clinical trials. The SBS recruited 948 patients from 8 countries. The study provides an insight into the symptom burden, expectations of treatment and patient outcomes in a „real world” clinical setting.

Patients and Methods:

Patients completed EORTC QLQ-C30, OV28, FACT-O/FOSI and MOST before each cycle of chemotherapy. At baseline, clinicians documented the symptoms of disease and adverse events related to prior therapy. They indicated the objectives of treatment as well as gave an estimation of response, the number of cycles they expected that patient would receive and predicted survival.

Results:

The median age was 63 years (range 23 – 100), median lines of chemotherapy was 2 (range 1 – 10). 60% of patients had PRR and 40% had PPS > 3 ROC. 89% of patients were ECOG 0 – 1. Palliation was the major indication for chemotherapy (70%). At baseline, most patients were symptomatic; 75% rated at least one symptom as moderated (on a 0 – 10scale) and 30% rated > 5 symptoms as moderate or worse. The top 10 symptoms and treatment concerns documented by patients on MOST were: fatigue (48%), abdominal swelling/bloating (38%), poor appetite (39%), abdominal pain/cramps (36%), pain (34%), shortness of breath (26%), constipation (26%), trouble eating (23%), indigestion (20%) and nausea (18%). 25% of patients with PRR-ROC stopped treatment in less than 8 weeks mainly due to progression/death. The median number of cycles and median PFS were 4 and 5.6 months in PPS≥ROC, and 3 and 3.7 month in PRR ROC respectively.

Conclusion:

The majority of patients receiving chemotherapy with PRR/PPS≥3ROC are symptomatic with a complex array of overlapping symptoms. The aim of treatment in most patients is to palliate symptoms. This underscores the importance of measuring symptom benefit in clinical trials in patients with PRR/PPS≥3ROC.

Clinical trials in PRR/PPS≥3ROC should include patient reported outcomes as primary/co-primary endpoints and report the proportion of patients who experience symptom benefit in addition to PFS.