Table 3.
Patient-reported outcome evidence with pembrolizumab in patients with breast and gynecologic cancers
| Indication | Trial name | Trial setting | Treatments | Instrument | Total N | PRO |
|---|---|---|---|---|---|---|
| TNBC | KEYNOTE-522 [89] | Previously untreated, high-risk, early-stage (stage II–III) | Pembrolizumab + chemotherapy (neoadjuvant) followed by pembrolizumab (adjuvant) vs placebo + chemotherapy (neoadjuvant) followed by placebo (adjuvant) |
EORTC QLQ-C30 and EORTC QLQ-BR23 (secondary objectives) EQ-5D (exploratory) |
Neoadjuvant PRO full analysis set (1145 for EORTC QLQ-C30, 1141 for EORTC QLQ-BR23, and 1146 for EQ-5D) Adjuvant PRO full analysis set (847 for EORTC QLQ-C30, 844 for EORTC QLQ-BR23, and 850 for EQ-5D) |
Neoadjuvant difference (95% CI) in LS mean score change from baseline to week 21a (pembrolizumab vs placebo) − 1.04 (− 3.46 to 1.38) for EORTC QLQ-C30 GHS/QoL, − 0.69 (− 3.13 to 1.75) for Emotional Functioning, and − 2.85 (− 5.11 to − 0.60) for Physical Functioning − 0.13 (− 1.92 to 1.65) for EORTC QLQ-BR23 Breast Symptoms − 1.61 (− 3.87 to 0.64) for EQ-5D VAS Adjuvant difference (95% CI) in LS mean score change from baseline to week 24a (pembrolizumab vs placebo) − 0.41 (− 2.60 to 1.77) for EORTC QLQ-C30 GHS/QoL, − 0.60 (− 2.99 to 1.79) for Emotional Functioning, and − 1.57 (− 3.36 to 0.21) for Physical Functioning 0.29 (− 2.05 to 2.63) for EORTC QLQ-BR23 Breast Symptoms − 0.59 (− 2.40 to 1.23) for EQ-5D VAS |
| TNBC | KEYNOTE-355 [159] | Previously untreated, late-stage (locally recurrent inoperable or metastatic) | Pembrolizumab + chemotherapy vs placebo + chemotherapy |
EORTC QLQ-C30 and EORTC QLQ-BR23 (secondary objectives) EQ-5D (exploratory) |
317 for PD-L1 CPS ≥ 10 PRO analysis set |
Difference (95% CI) in LS mean score change from baseline to week 15a (PD-L1 CPS ≥ 10, pembrolizumab vs placebo) − 1.81 (− 6.92 to 3.30) for EORTC QLQ-C30 GHS/QoL, − 1.43 (− 7.03 to 4.16) for Emotional Functioning, and − 1.05 (− 6.59 to 4.50) for Physical Functioning 0.18 (− 5.04 to 5.39) for EQ-5D VAS Similar between-group differences in LS mean change from baseline to week 15a in EORTC QLQ-BR23 functional (body image, sexual functioning, sexual enjoyment, and future perspective) and symptom (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss) scales/items |
| TNBC | KEYNOTE-355 [91] | Previously untreated, late-stage (locally recurrent inoperable or metastatic) | Pembrolizumab + chemotherapy vs placebo + chemotherapy | Q-TWiST | 323 |
Difference (95% CI) in mean Q-TWiST (PD-L1 CPS ≥ 10, pembrolizumab vs placebo) 3.7 (1.0‒6.3) mo at 44 mo and 4.3 (1.0‒7.3) mo at 52 mo corresponding to gains of 18% (P = 0.003) and 20% (P = 0.004), respectively |
| Endometrial cancer | KEYNOTE-158 [92] | Previously treated, advanced MSI-H/dMMR | Pembrolizumab | EORTC QLQ-C30 and EQ-5D-3L (exploratory) | 63 for overall cohort and 35 for CR/PR cohort |
Mean (95% CI) improvement from baseline to week 9b (overall cohort) 6.08 (0.71‒11.46) for EORTC QLQ-C30 GHS/QoL 6.00 (2.25‒9.75) for EQ-5D-3L VAS Mean (95% CI) improvement from baseline to week 9b (CR/PR cohort) 11.67 (5.33‒18.00) for EORTC QLQ-C30 GHS/QoL 9.11 (5.24‒12.98) for EQ-5D-3L VAS |
| Endometrial cancer | KEYNOTE-775 [93] | Previously treated, advanced, recurrent, or metastatic | Pembrolizumab + lenvatinib + vs chemotherapy |
EORTC QLQ-C30 GHS/QoL (secondary) EORTC QLQ-C30 (other scales), EORTC QLQ-EN24, and EQ-5D-5L (exploratory) |
752 for PRO full analysis set |
Difference (95% CI) in LS mean change from baseline to week 12a (pembrolizumab + lenvatinib vs chemotherapy) 1.01 (− 2.28 to 4.31) for EORTC QLQ-C30 GHS/QoL and − 0.09 (− 3.08 to 2.90) for Physical Functioning − 2.29 (− 5.03 to 0.45) for EORTC QLQ-EN24 Urological Symptoms 2.35 (− 0.44 to 5.14) for EQ-5D-5L VAS |
| Cervical cancer | KEYNOTE-826 [94] | Previously untreated, persistent, recurrent, or metastatic | Pembrolizumab + chemotherapy vs placebo + chemotherapy |
EORTC QLQ-C30 GHS/QoL (secondary) EORTC QLQ-C30 (other scales), EORTC QLQ-CX24, and EQ-5D-5L (exploratory) |
566 for PRO full analysis set |
Difference (95% CI) in LS mean change from baseline to week 30a (pembrolizumab vs placebo) 1.0 (− 2.7 to 4.7) for EORTC QLQ-C30 GHS/QoL and − 2.1 (− 6.0 to 1.8) for Physical Functioning 1.8 (− 1.6 to 5.1) for EQ-5D-5L VAS Similar between-group differences in LS mean change from baseline to week 30a in EORTC QLQ-CX24 symptom experience, sexual worry, peripheral neuropathy, menopausal symptoms, and lymphedema Median time to deterioration in EQ-5D-5L VAS not reached with pembrolizumab vs 7.7 mo with placebo (HR 0.75 [95% CI, 0.58–0.97) |
5D-3L 5-Dimension 3-Level, 5D-5L 5-Dimension 5-Level, CPS combined positive score, CR complete response, dMMR mismatch repair deficient, EORTC European Organisation for Research and Treatment of Cancer, EQ EuroQol, GHS/QoL global health status/quality of life, HR hazard ratio, LS least squares, mo months, MSI-H microsatellite instability-high, PD-L1 programmed cell death ligand 1, PR partial response, PRO patient-reported outcome, QLQ-BR23 Breast Cancer-Specific Quality of Life Questionnaire, QLQ-C30 Quality of Life Questionnaire–Core 30, QLQ-CX24 Quality of Life Questionnaire–Cervical Cancer, QLQ-EN24 Quality of Life Questionnaire–Endometrial Cancer, Q-TWiST Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment, TNBC triple-negative breast cancer, VAS visual analogue scale
aThe prespecified primary PRO analysis time point of interest was defined as the latest time at which there was ≥ 60%/80% completion/compliance
bPrespecified time point of interest