PRIMA Trial Finds QoL Not Reduced Despite Toxicities Observed in Patients with Gynecologic Malignancies

According to a subanalysis of the PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial, quality of life (QoL) according to patient-reported outcomes (PROs) was not reduced despite treatment toxicities in those with ovarian, primary peritoneal, or fallopian tube cancer treated with niraparib (Zejula) versus placebo.

Results from the subanalysis were presented by Bhavana Pothuri, MD, during the ESMO 2020 Virtual Congress.

PRIMA was an ongoing a randomized, double-blind, placebo-controlled phase 3 trial in which patients with newly diagnosed ovarian cancer who were at high risk for recurrence after responding to frontline platinum-based chemotherapy were enrolled. Patients were randomized in a 2:1 fashion to receive niraparib at a dose level based on body weight and platelet count or matching placebo. Study treatment was administered once daily continuously over a 28-day cycle.

The primary end point explored in the study was progression-free survival (PFS) by blinded independent committee review and secondary end points included overall survival (OS) and PROs. Stratification in PRIMA was dependent on whether or not patients had neoadjuvant chemotherapy, whether patients’ best response to first-line therapy led to a complete response (CR) or partial response (PR), homologous recombination deficiency (HRD) status, and the companion diagnostic used for each patient.

The instruments used to assess PROs in the study included the Functional Ovarian Symptoms Index (FOSI), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the EORTC Questionnaire Ovarian Cancer Module (EORTC QLQ-OV28), and the EurQol 5-Dimension 5-Level (EQ-5D-5L) assessment.

FOSI was utilized to evaluated symptoms including fatigue, nausea, bloating, worry, pain, vomiting, cramping, and QoL. The trial had an overall compliance rate of 80% with comparable FOSI scores observed across both the niraparib and placebo cohorts.

On a functional scale, EORTC QLQ-C30 was used to assess physical, social, role, cognitive, and emotional function. EORTC QLQ-C30 was also employed to evaluate symptoms such as nausea/vomiting, pain, fatigue, dyspnea, insomnia, appetite loss, constipation, and diarrhea, as well as financial difficulties.

The functional purpose of utilizing the EORTC QLQ-OV28 was to evaluate PROs related to body image, sexuality, and patients’ attitudes toward their disease and treatment with niraparib versus placebo. In terms of symptoms, EORTC QLQ-OV28 assessed abdominal/gastrointestinal conditions, peripheral neuropathy, hormonal/menopausal condition, hair loss, and other chemotherapy adverse events (AEs).

The EQ-5D-5L instrument was utilized to assess the state of each patient’s health in 5 domains, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

All instruments score PROs on a scale between 0 and 100. With the FIOS instrument, a higher score determined better symptoms. A higher symptom score with the EORTC QLQ-C30 and EORTC-QLQ-OV28 instruments indicated worse symptoms, while high QOL and functioning score for both indicated better outcomes.

In the FOSI assessment, patients responded to questions that asked about lack of energy, nausea, vomiting, or stomach cramps. In the niraparib and placebo arms, mean FOSI health utility index (HUI) scores were similar. Moreover, both arms had similar overall FOSI-assessed symptoms.

The EORTC QLQ-C30 questionnaire also demonstrated similar scores between the 2 study arms. Patients in the niraparib group versus the placebo group also reported no differences in QoL or pain and fatigue. Additionally, the EORTC QLQ-QV28 assessment for the cohort of patients with ovarian cancer showed no difference between the 2 arms in terms of abdominal symptoms and chemotherapy-related toxicities.

For the final questionnaire, EQ-SD-SL, the HUI-assessed change from baseline was not meaningfully different in the niraparib arm versus the placebo arm. This was also true for the EQ-SD-SL scores that were obtained using a visual analog scale.

The PROs results from PRIMA were found to be consistent with the phase 3 ENGOT-OV16/NOVA trial (NCT01847274) of niraparib maintenance in patients with platinum-sensitive, recurrent ovarian cancer considering that QoL was not negatively impacted. QoL remained positive in patients, even with the emergence of grade 3 or higher hematologic AEs.

Reference:

Pothuri B, Han S, Chase D. et al. Patient-reported outcomes (PROs) in patients (pts) receiving niraparib in the PRIMA/ENGOT-OV26/GOG-3012 trial. Presented at 2020 Virtual ESMO Congress; September 19-October 21, 2020; Virtual. Abstract 810MO.