Is it time to change the primary endpoint in clinical trials in recurrent ovarian cancer (ROC)? Symptom burden and outcomes in patients with platinum resistant/refractory (PRR) and potentially platinum sensitive ROC receiving ≥3 lines of chemotherapy (PPS) – The Gynecologic Cancer Intergroup (GCIG) Symptom Benefit Study (SBS). (#167)
Aims. The primary endpoint for clinical trials in PRR/PPS ROC is progression free survival (PFS) and symptom benefit is not typically measured or reported. The primary aim of GCIG SBS is to validate a patient-reported outcome measure (PROM), the MOST (Measure of Ovarian Symptoms and Treatment concerns), to assess symptom benefit from palliative chemotherapy (PC). The secondary aims provide insights into symptom burden, patients’ and clinician’s expectations of treatment and outcomes in a “real world” setting. The SBS recruited 949 patients.
Methods. Patients with PRR/PPS ROC completed 4 PROMs before each cycle of chemotherapy. They reported expectation of symptom improvement. Clinicians documented the indications for PC, symptoms at baseline, adverse events and estimated the number of cycles patients would receive.
Results. Palliation was the major indication for chemotherapy. The mean number of prior regimens was 2.6 (range 1-10). 60% of the patients had PRR and 40% had PPS ROC. At baseline, most patients were symptomatic: 75% rated at least one symptom as moderate (≥5 on a 0-10 scale) and 50% rated >5 symptoms moderate or worse. The symptoms included pain, fatigue, anorexia, abdominal distension, dyspnea, and constipation. Many patients had symptoms related to prior chemotherapy (e.g. neuropathy in 28%). Most patients had high expectations of symptom benefit from chemotherapy. 36% of the patients received the predicted number of cycles: 51% stopped within 2 cycles due to progression, death (17%), adverse events (7%) or patient/physician preference. The median number of cycles and median PFS were 4 months and 5.6 months in PPS ROC, and 3 months and 3.7 months in PRR ROC, respectively.
Conclusions. Patients with PRR/PPS ROC reported a number of significant baseline symptoms. They had high expectations of symptom improvement, but many progressed rapidly. The results underscore the importance of incorporating PROMs and the inclusion of symptom benefit as primary endpoints in trials in patients with PRR/PPS ROC.