KEYNOTE-522 Trial of Pembrolizumab Does Not Negatively Affect HRQOL Outcomes in TNBC

Pembrolizumab in the neoadjuvant and adjuvant settings demonstrated similar health-related quality-of-life scores in patients with triple-negative breast cancer when compared with placebo.

Pembrolizumab (Keytruda) given to patients with early-stage, triple-negative breast cancer (TNBC) showed similar scores across global health score (GHS), function, and breast symptom domains, compared with those given placebo, according to a patient-reported outcomes (PROs) analysis of the KEYNOTE-522 (NCT03036488) trial presented during the 2022 European Society of Medical Oncology Congress.

“Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in statistically significant and clinically meaningful improvement in pathological complete response [pCR] and event-free survival [EFS] vs neoadjuvant chemotherapy alone in patients with early-stage TNBC,” Rebecca Dent MD MSc, senior consultant at the National Cancer Center in Singapore, said in a presentation of the findings. “Together with the efficacy and safety findings of KEYNOTE-522, these PRO results support neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as an effective standard-of-care treatment regimen in this setting, without meaningful impact on health-related quality of life [HRQOL],” she added.

The KEYNOTE-522 study was designed to assess the efficacy of pembrolizumab in adults with newly diagnosed TNBC. Key eligibility criteria included a TNBC diagnosis with either T1c N1/2 or T2/4 N0-2 tumors, an ECOG performance status of 0 or 1, and a tissue sample for PD-L1 assessment.

The 1174 patients who enrolled were randomly assigned 2:1 to receive either pembrolizumab or placebo, plus chemotherapy, during the neoadjuvant phase, and monotherapy pembrolizumab or placebo in the adjuvant phase. During the neoadjuvant phase, which encompassed all treatments leading up definitive surgery, patients received carboplatin plus paclitaxel for the first 4 cycles, (12 weeks of treatment), followed by doxorubicin or epirubicin

plus cyclophosphamide for the next 4 cycles (12 weeks of treatment). Following surgery, patients received adjuvant treatment for 9 cycles (27 weeks). Those who received pembrolizumab were administered a dose of 200 mg once every 3 weeks.

The primary end points of the trial were pCR and EFS in the intention-to-treat population as assessed by a local pathologist. Secondary end points included PROs. To measure these, investigators leveraged the European Organization for Research and Treatment of Cancer Quality of Life Core 30 questionnaire (EORTC QLQ-C30) and EORTC QLQ-BR23, which are oncology-specific and breast cancer-specific, respectively, as well as the EuroQol-5D utility score EQ-5D. Patients were asked to complete these assessments before treatment for cycles 1 (baseline), 5, and 8 during the neoadjuvant phase. Following surgery, they were asked to complete the assessments every 12 months for 2 years or until disease progression or recurrence.

The differences in least squares mean change from baseline at primary analysis were assessed via a constrained longitudinal model. No alpha was assigned. For each PRO assessment, scores ranged from 0 to 100, and meaningful change was defined of a threshold change of greater than 10 points.

At data cutoff, the completion rate, or the number of patients who completed at least 1 score/term at each time point over the number of patients in the PRO full analysis set population, was greater than 60%. The compliance rate, or the number of patients who completed at least 1 score/item at each time point over the number of patients expected to complete at each time point, was greater than 80%.

In the neoadjuvant phase, at week 21, the percentage of patients who completed at least 1 PRO measurement was 80.7% in both the experimental (n = 762) and control arms (n = 383). The compliance rate between the 2 arms was 89.4% vs 88.5%, respectively. Moreover, following surgery, the completion rate between the pembrolizumab and placebo arms were 82.4% and 80.8%, respectively. The compliance rate was 91.7% vs 88.3%, respectively.

In the neoadjuvant phase of the trial, the LS mean score change from baseline (95% CI) was comparable between the 2 arms in GHS and QOL, with a mean change of –1.04 between the 2 arms (–3.46 to 1.38). Similarly, emotional functioning and physical functioning were similar affected, the mean changes was –0.69 (–3.13 to 1.75), and –2.85 (–5.11 to –0.60), respectively. In terms of breast cancer-specific symptoms, the mean change was –0.13 (–1.92 to 1.65), and changes in visual analog score (VAS) was –1.61 (–3.87 to 0.64).

These findings were also consistent with the adjuvant baseline scores. The LS mean changes score from baseline (95% CI) was –0.41 (–2.60 to 1.77) for GHS/QOL, –0.60 (–2.99 to 1.79) for emotional functioning, and –1.57 (–3.36 to 0.21) for physical functioning. The mean change for breast cancer-specific symptoms was 0.29 (–2.05 to 2.63) and the mean change in VAS was –0.59 (–2.40 to 1.23).

“These [data] are an important component of this trial [because] we have an arm of patients who are not getting an active drug,” Dent noted. “The mean scores are similar between the 2 groups; no meaningful difference from the baseline, and again, this is across all the domains and all the scales that were measured: quality of life, emotional functioning, physical functioning, [and] breast symptoms.”

“For many of us, these [data are] was very reassuring,” she added.

Ultimately, the combined PROs from both the neoadjuvant and adjuvant phases support the use of pembrolizumab in this patient population, with pooled data across GHS, functional, and breast cancer symptoms domains confirming that pembrolizumab did not have a meaningful effect on HRQOL, Dent concluded.

Dent R, Cortés J, Pusztai L, et al. HRQoL with neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: results from KEYNOTE-522. Presented at: ESMO Congress 2022; September 9-13, 2022; Paris, France. Abstract 135MO.