Patient-reported outcomes (PRO) support a favorable benefit-risk balance for pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab (Avastin) as first-line treatment for patients with cervical cancer. Persistent, Recurrent or Metastatic Uterus, According to Updated Results from the KEYNOTE-826 Phase 3 Randomized Trial (NCT03635567) presented at 2022 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.
Global change in geometric least squares mean from baseline to 30 weeks according to the European Organization for Research and Treatment of Cancer (EORTC): Quality of Life Questionnaire-Core 30 (QLQ-C30) for the state (GHS)/quality of life (QOL)) was -0.3 (95% CI, -3.1 to 2.6) in the pembrolizumab group versus -1.3 (95% CI , -4.2 to 1.7) in the placebo group (least squares mean difference, 1.01; 95% CI, -2.7 to 4.7). Although the difference was not statistically significant, pembrolizumab was numerically better than placebo in terms of quality of life.
“Overall KEYNOTE-826 results support pembrolizumab plus chemotherapy with or without bevacizumab as the new standard of care for women with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 [combined positive score] of 1 or more,” said Bradley Monk, MD, professor in the department of obstetrics and gynecology, University of Arizona College of Medicine, in his presentation of the data.
Eligible patients were randomized 1:1 to receive 200 mg intravenous pembrolizumab or placebo every 3 weeks for 35 cycles plus intravenous paclitaxel, cisplatin, or carboplatin for up to 6 cycles with or without 15 mg/kg bevacizumab intravenously every 3 weeks.
The co-primary endpoints of the KEYNOTE-826 trial were progression-free survival (PFS) and overall survival (OS). Primary secondary endpoints included overall response rate, duration of response, PFS rate at 12 months, safety, and changes from baseline in QOL questionnaire scores. Changes in PROs were an exploratory endpoint of the research.
The main eligibility criteria required that patients have persistent, recurrent or metastatic cervical cancer not amenable to curative treatment, no prior systemic chemotherapy and an ECOG performance score of 0 or 1.
The co-primary endpoints of the KEYNOTE-826 trial have already been reportedshowing that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab significantly improved PFS and OS compared to placebo while maintaining a tolerable safety profile.
“KEYNOTE-826 improved progression-free survival and overall survival, but it all depends on patient experience,” Monk explained in his presentation of the data. “We need to contextualize this clinical benefit to see if it satisfies the clinical risk-benefit ratio.”
To measure the PROs, the investigation team used the EORTC questionnaire: QLQ-C30, EuroQol 5-Dimension 5-Level visual analog scale (EQ-5D-5L VAS) and the EORTC QLQ-CX24 Cervical Cancer questionnaire which have were administered before each cycle. from treatment until cycle 14, then after each subsequent cycle, at the end of treatment and at the follow-up safety visit.
All PRO endpoints were pre-specified, with change in EORTC QLQ-C30 global health status labeled as a key secondary endpoint. To ensure data reliability, compliance rates of 60% and 80% were required in the pembrolizumab and placebo groups, respectively.
At 30 weeks, completion and adherence rates were sufficient among the pembrolizumab and placebo groups to create the study endpoint.
Looking at the EORTC QLQ-C30 scale, physical, role, cognitive, and social functioning were slightly worse in the pembrolizumab group compared to the placebo group. According to the QLQ-CX24 scale, peripheral neuropathy was worse in the placebo group than in the pembrolizumab group.
In the analysis of time to true deterioration (TTD), with deterioration defined as a 10-point decrease in PRO scores, the pembrolizumab arm performed numerically better than the placebo arm in most measures. For GHS/QOL by EORTC QLQ-C30, the median TTD in the pembrolizumab arm was not reached (NR; 95% CI, 13.4-NR) compared to 12.9 months (95% CI , 6.6-NR) in the placebo arm (HR , 0.84; 95% CI, 0.65-1.09; P = 0.1851). For the EQ-5D-5L VAS, the median TTD in the pembrolizumab arm was NR (95% CI, 17.2-NR) versus 7.7 months (95% CI, 6.0-NR) in the placebo arm (HR, 0.75; 95% CI, 0.58-0.97; P = 0.0273).
For physical functioning according to the EORTC QLQ-C30, the proportion of patients with improved PROs was 42.1% versus 26.8% in the placebo arm. For the EQ-5D-5L VAS, the proportion of patients with improved PROs was 42.8% and 36.4% in the pembrolizumab and placebo groups, respectively.
Monk BJ, Tewari KS, Hasegawa CK, et al. Patient-reported results from the Phase 3 randomized, double-blind, KEYNOTE-826 trial comparing pembrolizumab plus chemotherapy versus placebo plus chemotherapy for the first-line treatment of persistent, recurrent, or metastatic cervical cancer. Presented at the 2022 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer; March 18-21, 2022; Phoenix, Arizona