Patient-reported outcomes in the randomized phase III IMagyn050/GOG3015/ENGOT-ov39 trial evaluating atezolizumab (atezo) with carboplatin/paclitaxel/bevacizumab for newly diagnosed ovarian cancer

Abstract

<h3>Objectives:</h3> Although primary results from the IMagyn050 trial showed no statistically significant improvement in progression-free survival (PFS) with atezo added to carboplatin/paclitaxel/bevacizumab (CPB) [Moore, ESMO 2020], the impact of this regimen on selected patient (pt)-reported ovarian cancer symptoms, function, and health-related quality of life (HRQoL) is unknown and the focus of this study. <h3>Methods:</h3> IMagyn050 is a double-blind randomized phase 3 trial evaluating the efficacy and safety of adding atezo/placebo to CPB followed by maintenance bevacizumab + atezo/placebo. The trial includes two cohorts: neoadjuvant chemotherapy (NACT) and primary surgery (PS). Pts complete EORTC QLQ-C30, QLQ-OV28, and FACT-G single-item GP5 at baseline (BL) and at regular intervals during treatment and follow-up. In NACT pts, prespecified responder analyses (using a ≥10-point cutoff for clinically meaningful change) assessed improvement in abdominal pain (OV28 item 31) and bloating (OV28 item 32) at week 9, comparing treatment arms by Cochran-Mantel-Haenszel (CMH) testing. Additional secondary objectives in the NACT and PS cohorts were assessments of function (physical, role, emotional, social) and HRQoL, as measured by QLQ-C30 functional and global health status/quality of life scales. Exploratory endpoints included mean change from BL in symptoms (QLQ-C30 and OV28) and treatment side-effect bother (FACT-G GP5) in both cohorts. <h3>Results:</h3> Of 1301 randomized pts, completion rates for each of the 3 questionnaires were 83-100% at BL and >85% on treatment. In NACT pts, mean BL scores were similar in the atezo vs placebo arms for abdominal pain (40.2 vs 44.8) and bloating (50.4 vs 56.3). At week 9, there was no difference between treatments in the proportion of NACT pts with ≥10-point improvement in either symptom (abdominal pain: 69/136 [51%] with atezo vs 77/142 [54%] with placebo, CMH p=0.56; bloating: 74 [54%] vs 89 [63%], CMH p=0.14). Results were consistent when restricted to NACT pts with sufficient BL symptoms to show ≥10-point improvement. There was no difference between treatments in the proportion of NACT pts with improvement in function or HRQoL at week 9. In the PS cohort, similar proportions of pts in each arm showed on-treatment improvement, stabilization, or deterioration in function and HRQoL. In both cohorts, neither arm showed meaningful changes from BL in treatment-related symptoms and similar proportions of pts in both arms reported being ‘a little bit' or ‘somewhat' bothered by treatment side effects while on therapy. <h3>Conclusions:</h3> Consistent with PFS results, there were no differences between arms in the proportion of NACT pts with a clinically meaningful improvement in abdominal pain and bloating after 3 cycles of bevacizumab-containing therapy. Pt-reported outcome analyses in both cohorts showed that adding atezo to CPB did not increase treatment burden for pts, thereby demonstrating the tolerability of this 4-drug regimen and providing further insight on the benefit-risk assessment of atezo.