HRQOL Data Support Pembrolizumab/Chemo in Recurrent/Metastatic Cervical Cancer

Pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab (Avastin) did not negatively affect health-related quality of life (HRQOL) in patients with persistent, recurrent, or metastatic cervical cancer, according to data on patient-reported outcomes from the phase 3 KEYNOTE-826 trial (NCT03635567).

"Not only is there a statistically significant and clinically meaningful improvement in overall survival [OS], but patient reported outcomes show that this is associated with favorable [QOL]. This transformational study demonstrates that these patients can live longer, as well as live better," according to an expert from the University of Arizona College of Medicine.

The least squares mean change in Quality-of-Life-Core 30 (QLQ-C30) global health status (GHS) scores from baseline to week 30 of treatment was –0.3 points (95% CI, –3.1 to 2.6) for patients receiving the pembrolizumab-based regimen and –1.3 points (95% CI, –4.2 to 1.7) for those receiving the placebo-based regimen.

The median time to true deterioration (TTD) in QLQ-C30 GHS-QOL was not reached (NR; 95% 13.4-NR) in the pembrolizumab group compared with 12.9 months (95% CI, 6.6-NR) in the placebo group (HR, 0.84; 95% CI, 0.65-1.09; P = .19). The median TTD for QLQ-C30 physical functioning score was 8.9 months (95% CI, 6.0-19.7) and 10.6 months (95% CI, 7.0-NR) in each respective treatment group (HR, 1.11; 95% CI, 0.87-1.42; P = .39).

Overall, 42% of patients in the pembrolizumab group and 29% of those in the placebo group experienced improved QLQ-C30 GHS-QOL scores at any point during the study.

“Pembrolizumab added to chemotherapy (plus or minus bevacizumab) has become the new preferred standard of care for treating [patients] with newly diagnosed stage IVB, persistent, or recurrent cervical cancer,” lead author Bradley J. Monk, MD, professor of Obstetrics & Gynecology in the Division of Gynecologic Oncology at the University of Arizona College of Medicine, stated in a written comment to CancerNetwork^®.

“Not only is there a statistically significant and clinically meaningful improvement in overall survival [OS], but patient reported outcomes show that this is associated with favorable [QOL]. This transformational study demonstrates that these patients can live longer, as well as live better.”

In the multi-center, randomized phase 3 KEYNOTE-826 trial, patients received treatment in 151 cancer treatment centers across 19 countries. Patients were randomly assigned 1:1 to receive 200 mg of pembrolizumab or matched placebo intravenously for up to 35 cycles plus 175 mg/m² of paclitaxel and 50 mg/m² of cisplatin or 5 mg/mL per minute of carboplatin area under the curve intravenously with or without 15 mg/kg of bevacizumab intravenously every 3 weeks.

The protocol-specified secondary patient-reported outcome was the change in QLQ-C30 GHS-QOL score from baseline. Exploratory patient-reported outcomes included the changes in patient-reported QOL as determined with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EuroQol-5 dimension-5 level (EQ-5D-5L) scale, and the EORTC cervical cancer module (QLQ-CX24).

The primary end points of the KEYNOTE-826 trial were OS and progression-free survival. Secondary end points included objective response rate, and duration of response. Investigators had highlighted safety and efficacy in previous reports of the trial.

The trial included a total of 617 patients, with 308 in the pembrolizumab group and 309 in the placebo group. Additionally, 45% of patients in the pembrolizumab group and 39% of those in the placebo group were non-White. Investigators noted that baseline characteristics were generally comparable between the 2 treatment groups.

Compliance and completion rates for patients in the pembrolizumab group and placebo group were at least 95% at baseline for the QLQ-C30, EQ-5D-5L, and QLQ-CX24 items. Over time, completion rates decreased to 44% of those in the pembrolizumab group and 34% in the placebo group at 51 weeks.

The least squares mean change in EQ-5D-5L scores from baseline to week 30 was 0.3 points (95% CI, –2.2 to 2.8) in the pembrolizumab group vs –1.5 points (95% CI, –4.1 to 1.1) in the placebo group (P = .29). The median TTD in terms of EQ-5D-5L scores was NR (95% CI, 17.2-NR) and 7.7 months (95% CI, 6.0-NR) in each respective group. Overall, 78% and 72% of patients in each group had improvements in EQ-5D-5L visual analogue scale at any point in the study (P = .033).

Scores for QLQ-CX24 subscales either decreased or remained unchanged from baseline to week 30 in the pembrolizumab and placebo groups, although patients in both groups experienced increases in scores for peripheral neuropathy from baseline to week 30. Additionally, a slightly higher proportion of patients in the pembrolizumab group had improved scores vs the placebo group for cervical symptoms such as lymphoedema, menopausal symptoms, and symptom experience. Most patients in the placebo group had deteriorating scores across most QLQ-CX24 scores.

Reference

Monk BJ, Tewari KS, Dubot C, et al. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo- controlled, phase 3 trial. Lancet Oncol. 2023;24(4):392-402. doi:10.1016/S1470-2045(23)00052-9