Pembrolizumab Plus Chemotherapy Does Not Significantly Affect QOL in PD-L1+ TNBC

The addition of pembrolizumab (Keytruda) to chemotherapy led to significant survival benefits without substantial deterioration in health-related quality of life (QOL) among patients with treatment-naïve, PD-L1–positive advanced triple-negative breast cancer (TNBC) according to results from the phase 3 KEYNOTE-355 trial (NCT02819518). Findings were presented during the European Society for Medical Oncology Breast Cancer Congress 2022.

Patients treated with pembrolizumab plus chemotherapy achieved statistically significant and clinically meaningful improvements in progression-free survival (PFS; HR, 0.73; 95% CI, 0.55-0.95; P = .0093) and overall survival (OS; HR, 0.65; 95% CI, 0.49-0.86; P = .0012) compared with chemotherapy alone in patients with a combined positive score (CPS) of at least 10. Additionally, no significant difference in the treatment arms were reported in general health status (GHS)/QOL, emotional functioning, and physical functioning according to patient reported outcome (PRO) measures from baseline to week 15 among patients with a PD-L1 combined positive score (CPS) of 10 or greater. Outcomes were measured using the Quality of Life Core 30 questionnaire (QLQ-C30).

“Together with the efficacy and safety findings of KEYNOTE-355, these PRO results support pembrolizumab plus chemotherapy as and effective standard-of-care treatment regimen for patients with locally recurrent, unresectable or metastatic TNBC whose tumors express PD-L1,” David W. Cescon, MD, PhD, a medical oncologist and clinical scientist at Princess Margaret Cancer Centre in Toronto, Canada, said during the presentation.

Patients in the pembrolizumab plus chemotherapy arm (n = 216) had a baseline GHS/QOL mean score of 67.54, comparable with the 64.54 mean score in the placebo plus chemotherapy arm (n = 100). The least squares (LS) mean changes from baseline were –2.69 (95% CI, –5.86-0.48) and –0.88 (95% CI, –5.41-3.64), respectively, for a mean between-group difference of –1.81 (95% CI, –6.92-3.30; P = .4865).

In terms of emotional functioning, the baseline mean score for patients in the pembrolizumab plus chemotherapy arm was 73.34 compared with 72.52 in the placebo plus chemotherapy arm. The LS mean scores were –0.75 (95% CI, –3.92-2.43) and 0.69 (95% CI, –4.07-5.44), respectively. The mean between-group difference was –1.43 (95% CI, –7.03-4.16; P = .6149).

The baseline mean scores for physical functioning were also similar between the 2 arms: 73.34 among patients in the pembrolizumab plus chemotherapy cohort and 78.30 for those in the placebo plus chemotherapy cohort. The LS mean scores were –6.76 (95% CI, –9.89 to –3.62) and –5.71 (95% CI, –10.41 to –1.01) respectively. The between-group difference was –1.05 (95% CI, –6.59-4.50; P = .7102).

In the analysis, PROs were assessed at baseline, prespecified time points throughout treatment, at the conclusion of treatment, and at the 30-day safety follow-up visit. The primary analysis time point was determined to be the latest point in the study when completion and compliance rates were at least 60% and at least 80%, respectively. The prespecified PRO end point of primary interest was the mean change in QLQ-C30 GHS/QOL scores from baseline to week 15.

Patients in the pembrolizumab plus chemotherapy arm had a QLQ-30 completion rate of 77.0% at week 15 compared with 70.0% in the placebo plus chemotherapy arm. QLQ-30 compliance rates at week 15 were 87.0% and 81.4%, respectively.

Additional results from the QOL analysis showed a minimal difference in terms of time to deterioration (TTD) between the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms. The median TTD by the QLQ-C30 GHS/QOL scale was 5.8 months (95% CI, 3.7-8.1) and 5.6 months (95% CI, 3.7-9.7), respectively, (HR, 1.00; 95% CI, 0.72-1.40). In the QLQ-C30 emotional functioning results, the median TTD was 9.3 months (95% CI, 6.4-11.7) and 15.5 (95% CI, 5.6–not reached), respectively (HR, 1.28; 95% CI, 0.88-1.85). Finally, by the QLQ-C30 physical functioning measure, the median TTD was 5.6 months (95% CI, 4.0-6.9) and 5.8 months (95% CI, 3.7-14.5), respectively (HR, 1.28; 95% CI, 0.90-1.77).

In terms of the EuroQol 5-dimension, 5-level questionnaire (EQ-5D) visual analog scale, the baseline mean score in the pembrolizumab plus chemotherapy arm was 72.19 compared with 72.56 in the placebo plus chemotherapy arm. The LS mean score changes from baseline were –5.45 (95% CI, –8.68 to –2.23) and –5.63 (95% CI, –10.22 to –1.04), respectively, for a LS mean between-group difference of 0.18 (95% CI, –5.04-5.39).

KEYNOTE-355 randomized adult patients with PD-L1-positive TNBC 2:1 to receive either pembrolizumab plus chemotherapy or placebo plus chemotherapy. Patients were stratified based on chemotherapy type (taxane vs gemcitabine-carboplatin), PD-L1 tumor expression (CPS ≥ 1 vs CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes vs no).

The trial had dual primary end points of OS and PFS in patients with PD-L1-positive tumors and in the intention-to-treat population. Secondary end points included overall response rate, duration of response, and change from baseline in PRO assessments by European Organization for Research and Treatment of Cancer QLQ-C30 and Quality of Life Breast cancer questionnaire (QLQ-BR23).

Safety results from the trial were consistent with the known profiles of each regimen with no new safety concerns identified. Grade 3-5 treatment-related adverse effects (AEs) were reported in 68.1% of patients in the pembrolizumab plus chemotherapy arm compared with 66.9% in the placebo plus chemotherapy arm. Immune-mediated AEs were not common in either arm, occurring in 5.3% and 0% of patients, respectively.

Reference

Cescon DW, Schmid P, Rugo HS, et al. Health-related quality of life (HRQoL) with pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as 1L treatment for advanced triple-negative breast cancer (TNBC): results from KEYNOTE-355. Presented at: European Society for Medical Oncology Breast Cancer Congress 2022. May 3-5, 2022; Berlin, Germany.