Messaggi chiave
- In KEYNOTE-355, l’aggiunta di pembrolizumab alla chemioterapia ha prodotto un miglioramento statisticamente significativo degli esiti di sopravvivenza in pazienti con carcinoma mammario triplo negativo in stadio avanzato (aTNBC) PD-L1 positivo (punteggio positivo combinato ≥10). In questa sede, si riportano i risultati degli esiti riferiti dai pazienti.
- L’analisi ha incluso 317 pazienti. Non sono state osservate differenze tra i due bracci in termini di variazione dal basale alla settimana 15 nei punteggi di stato di salute globale/qualità della vita (QoL), funzionamento fisico e funzionamento emotivo misurati con questionario QLQ-C30, né nei punteggi VAS misurati con questionario EQ-5D. Analogamente, non sono emerse differenze nel tempo al peggioramento dei punteggi QLQ-C30 di stato di salute globale/QoL, funzionamento emotivo o funzionamento fisico.
- Sebbene il trattamento sperimentale non si sia associato a un miglioramento della QoL, i risultati della presente analisi, insieme ai dati di efficacia e sicurezza dello studio, supportano ulteriormente la combinazione di pembrolizumab più chemioterapia come regime standard di cura nel trattamento di prima linea di pazienti con aTNBC PD-L1-positivo.
Abstract
Background
- In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10.
- We report patient-reported outcomes from KEYNOTE-355.
Methods
- Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator’s choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin).
- The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified.
- Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment.
- Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively).
- Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline.
Results
- Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100).
- There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning.
Conclusions
- Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).