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BACKGROUND: In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab+chemotherapy then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522. METHODS: Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel+carboplatin then 4 cycles of doxorubicin (or epirubicin)+cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. EORTC QLQ-30 and QLQ-BR23 were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1/cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with ≥60%/80% completion/compliance were assessed using a longitudinal model (no alpha error assigned). RESULTS: Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab+chemotherapy [N = 762] vs placebo+chemotherapy [N = 383]) in LS mean change from baseline to week 21 in QLQ-C30 GHS/QoL, emotional functioning, and physical functioning were -1.04 (95% CI, -3.46 to 1.38), -0.69 (95% CI, -3.13 to 1.75), and -2.85 (95% CI, -5.11 to - 0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [N = 539] vs placebo [N = 308]) in LS mean change from baseline to week 24 were -0.41 (95% CI, -2.60 to 1.77), -0.60 (95% CI, -2.99 to 1.79), and -1.57 (95% CI, -3.36 to 0.21). CONCLUSIONS: No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab+chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo+chemotherapy in early-stage TNBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03036488.
RESUMEN
Aim: A systematic review and network meta-analysis (NMA) was performed to evaluate the efficacy of first-line treatments for locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) patients. Materials & methods: Databases were searched for randomized controlled trials evaluating first-line treatments for locally recurrent unresectable or metastatic TNBC patients. NMA was performed to estimate relative treatment effects on overall and progression-free survival between pembrolizumab + chemotherapy and other interventions. Results: NMA including eight trials showed that the relative efficacy of pembrolizumab + chemotherapy was statistically superior to that of other immunotherapy- or chemotherapy-based treatment regimens. Conclusion: Pembrolizumab + chemotherapy confers benefits in survival outcomes versus alternative interventions for the first-line treatment of locally recurrent unresectable or metastatic TNBC patients.
Clinical value of initial treatments for patients with advanced triple-negative breast cancerWhat is this article about? Around 15% of breast cancer patients have the triple-negative breast cancer (TNBC) subtype, which has the worst prognosis. Treatments targeting the immune system, such as pembrolizumab, were recently found to improve the outcomes of patients with cancer that is at an advanced stage or resistant to standard therapies. However, clinical trials evaluating the efficacy of cancer treatments typically compare only two alternative treatments. Therefore, we conducted this study to understand the relative efficacy of several commonly used initial treatments for advanced TNBC by indirectly comparing the results of all available clinical trials that were sufficiently similar. We identified trials by systematically searching the medical literature and analyzed the results of several clinical trials together to estimate the efficacy of pembrolizumab + chemotherapy compared with several other initial treatment regimens for patients with advanced TNBC.What were the results? We identified eight randomized controlled trials evaluating treatment regimens containing chemotherapeutic or immunotherapeutic agents in patients with previously untreated advanced TNBC. Considering all these trials together, pembrolizumab + chemotherapy was found to prolong patient survival to a greater extent than several other treatment regimens including carboplatin, docetaxel, paclitaxel, nab-paclitaxel/paclitaxel, bevacizumab + paclitaxel, ixabepilone + paclitaxel and ixabepilone + bevacizumab depending on the specific set of trials analyzed.What do the results of the study mean? These results indicate that pembrolizumab + chemotherapy has beneficial effects on patient survival compared with other initial treatment regimens for patients with advanced TNBC.
