An analysis of patient-reported outcomes in the phase 3 RUBY trial supports dostarlimab use in patients with primary advanced or recurrent endometrial cancer.
An analysis of patient-reported outcomes (PROs) from the phase 3 ENGOT-EN6/GOG3031/RUBY trial (NCT03981796) suggest that dostarlimab-gxly (Jemperli) does not negatively affect health-related quality-of-life (HRQOL) outcomes when used in combination with carboplatin/paclitaxel (CP) in patients with primary advanced or recurrent endometrial cancer. Findings were presented during the 2023 American Society of Clinical Oncology Meeting.
PROs were similar between patients who received the combination vs those who received CP plus placebo after 3 years of treatment. Measurements were collected at baseline, on day 1 of each treatment cycle, and at the end of treatment. For each scale assessed—global, pain, fatigue, and physical function—the changes from baseline to cycle 7, the start of the monotherapy phase, and cycle 13, the start of the second year of monotherapy treatments, were calculated and mixed models were generated to measure the least-squares mean change (LSM).
Among patients withmismatch repair deficient (dMMR)/microsatellite instability–high (MSI-H) disease who received dostarlimab plus CP, numerical improvements from baseline were observed at cycle 7 in global health score/quality of life (GHS/QOL), physical functioning, role functioning, pain, and back/pelvis pain. When compared with the improvements in the placebo plus CP arm, these improvements were deemed nominally significant. The LSMs were 9.4 (standard error [SE], 3.72; P = .01), 7.5 (SE, 3.61; P = .04), 11.7 (SE, 5.23; P = .03), –16.8 (SE, 4.78; P = .01), and –12.1 (SE, 5.55; P = .03), respectively.
In the overall population, no differences were reported across these symptom scales between the 2 arms at cycle 7 or 13.
“Dostarlimab plus CP significantly improved PFS while maintaining HRQOL in both the dMMR/MSI-H and overall populations,” Mansoor Raza Mirza MD, chief oncologist in the Department of Oncology in Rigshospitalet, Copenhagen University Hospital, Denmark, said in a presentation of the findings.
Previous reports from the randomized, double-blind, multicenter study, RUBY trial showed that dostarlimab plus CP met the primary end point of the phase 3 RUBY trial doubling the 2-year progression-free survival (PFS) rate at 36.1% (95% CI, 29.3%-42.9%) compared with 18.1% (95% CI, 13%-23.9%) with placebo plus CP (HR, 0.64; 95% CI, 0.51-0.80, P < .001). Moreover, although overall survival (OS) data are not mature, there is a clinically meaningful trend towards improved OS, according to investigators. Though they hypothesize that this treatment regimen will improve outcomes for this patient population, PRO assessments are an important variable in assessing how this treatment benefits patients, as monitoring PROs allows investigators to better understand and potentially improve patient HRQOL.
The RUBY trial enrolled 494 patients with primary advanced or recurrent endometrial cancer. These patients were randomly assigned to receive either 500 mg intravenous (IV) dostarlimab plus CP or placebo plus CP every 3 weeks for 6 cycles, followed by either 1000 mg IV dostarlimab or placebo monotherapy every 6 weeks for up to 3 years, or until disease progression. The primary end points were PFS and OS. Secondary outcomes included PFS by blinded independent control review, time to second disease progression, duration of response, disease control rate, safety, and HRQOL. PRO assessments were collected through the European Organization for the Research and Treatment of Cancer Quality of Life (EORTC) QLQ-C20 and the Quality-of-Life Questionnaire - Endometrial Cancer Module (QLQ-EN24) questionaries.
Mirza noted that when interpreting these PRO measures it is important to bear in mind that higher scores indicate better HRQOL and better functioning in terms of QOL/functional scales, and that higher scores indicate worse symptoms when assessing domains such as pain, muscular pain, and hair loss.
The PRO completion rates were high across the different time points. At baseline, the completion rates in the experimental and control arms were 95.9% to 97.4% and 94.0% to 97.2%, respectively. At cycle 7 they were 97.3% to 98.3%, and 99.4% to 99.5%, respectively, and at cycle 13, they were 97.7% to 98.9% and 96.6% to 96.6%. By the end of treatment, the rates were 75.4% to 75.8% and 81.2% to 82.1% in the dostarlimab and placebo groups, respectively.
At cycle 7, there were no significant differences between thedostarlimab and placebo arms in the dMMR/MSI-H population in terms of mean change in fatigue, equaling an LSM of –7.6 (SE, 4.41; P = .09). In the overall population, no significant differences were reported at cycle 7 in terms of pain, fatigue, or back/pelvis pain between the experimental and control arms. The LSMs for these scales were –1.9 (SE, 2.29; P = .40), 2.4 (SE, 2.11; P = .25), and –3.5 (SE, 2.57; P = .17), respectively.
Also at cycle 7, no significant differences were reported in the dMMR/MSI-H cohorts for a mean change in emotional, cognitive, and social functioning. The LSMs across these scales were 3.2 (SE, 3.78; P = .40), 4.2 (SE, 3.78; P = .27), and 5.6 (SE, 4.82; P = .24). In the overall population, no significant differences were reported at cycle 7 for a mean change in QOL nor physical, role, emotional, cognitive, or social functioning. The LSMs across these measurements were 0.4 (SE, 1.79; P = .84, 0.3 (SE, 1.86; P = .85), –2.2 (SE, 2.50; P = .38), –1.0 (SE, 1.72; P = .57), 1.5 (SE, 1.82; P = .40), –1.5 (SE, 2.29; P = .52).
No significant differences between dostarlimab and placebo were reported at cycle 13 in the dMMR/MSI-H cohorts for a mean change in baseline in pain, fatigue, or back and pelvis pain. The LSMs were –8.3 (SE, 6.76; P = .22), –2.0 (SE, 5.00; P = .69), and –9.76 (SE, 6.11; P = .12), respectively. This finding was consistent in the overall population, where the LSMs were 2.0 (SE, 3.38; P = .55), 5.7 (SE, 3.06; P = .06), and –0.3 (SE, 3.56; P = .94), respectively.
Similarly, no significant differences between dostarlimab and placebo were reported at cycle 13 in either the dMMR/MSI-H or overall populations for global health scores, physical functioning, role functioning, emotional functioning, cognitive functioning, or social functioning. In the former, the LSMs across these 6 scales were 7.6 (SE, 3.97; P = .06), 7.9 (SE, 4.85; P = .10), 4.8 (SE, 7.27; P = .51), 4.7 (SE ,4.16; P = .27), –0.7 (SE, 4.24; P = .87), and 6.1 (SE, 6.41; P = .34), respectively. In the overall populations, the LSM were –2.6 (SE, 2.26; P = .26), –0.1 (SE, 2.37; P = .96), –4.9 (SE, 3.62; P = .18), –1.1 (SE, 2.32; P = .63), –0.9 (SE, 2.11; P = .66), and –3.8 (SE, 3.30; P = .25).
“These results further support the use of dostarlimab plus CP as a standard of care in patients with primary advanced or recurrent endometrial cancer,” Mirza concluded.
Editor’s Note: This research was supported by Pharmaceutical/Biotech Company and GSK. Dr Mirza also reported a number of relationships with pharmaceutical companies.
Mirza MR, Powell MA, Lundgren C, et al. Patient-reported outcomes (PROs) in primary advanced or recurrent endometrial cancer (pA/rEC) for patients (pts) treated with dostarlimab plus carboplatin/paclitaxel (CP) as compared to CP in the ENGOT-EN6/GOG3031/RUBY trial. J Clin Oncol. 2023;41(suppl 16):5504. doi:10.1200/JCO.2023.41.16_suppl.5504