RESUMO
BACKGROUND: We performed a network meta-analysis of randomized controlled trials (RCTs) to indirectly compare the efficacy of different targeted agents with fulvestrant for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor type 2-negative (HER2-) advanced breast cancer (ABC) following progression on prior endocrine therapy. METHODS: The titles/abstracts were searched from the PubMed, EMBASE, and the Cochrane Library databases for RCTs to evaluate the efficacy of palbociclib plus fulvestrant vs alternative targeted therapies plus fulvestrant for postmenopausal HR+/HER2- ABC following progression on prior endocrine therapy. In addition, the primary measured outcome was progression-free survival (PFS) and objective response rate. The surface under the cumulative ranking (SUCRA) value of each treatment was calculated to achieve the best ranking for each treatment. RESULTS: A total of 11 studies, including 4,178 patients in the network meta-analysis, were included and analyzed. In terms of the pooled hazard ratios (HRs) for PFS, palbociclib plus fulvestrant was superior to other target agents plus fulvestrant (HR=0.62, 95% credible interval [CrI]: 0.40-0.96; HR=0.62, 95% CrI: 0.47-0.96; for pictilisib plus fulvestrant and buparlisib plus fulvestrant, respectively). Ribociclib plus fulvestrant has no difference in abemaciclib plus fulvestrant and palbociclib plus fulvestrant (HR =1.02, 95% CrI =0.72-1.45; HR =1.22, 95% CrI =0.84-1.78). In terms of objective response rate, compared with placebo plus fulvestrant, abemaciclib plus fulvestrant, dovitinib plus fulvestrant, buparlisib plus fulvestrant, and palbociclib plus fulvestrant had a significant difference (odds ratio [OR] =2.84, 95% CrI =1.91- 4.31; OR =3.62, 95% CrI =1.21-12.48; OR =1.80, 95% CrI =1.25-2.60; and OR =2.52, 95% CrI =1.43- 4.72, respectively). CONCLUSION: According to the present study, palbociclib plus fulvestrant may be the optimal treatment for HR+/HER2- postmenopausal women with ABC after disease progression following endocrine therapy.
RESUMO
BACKGROUND: Endocrine therapy is the cornerstone treatment for patients with hormone receptor-positive advanced breast cancer. We aimed to assess the effectiveness of various first-line endocrine monotherapies or combinations to determine the optimal sequence in a network meta-analysis. MATERIALS AND METHODS: We searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) from inception up to November 21, 2017. We included only RCTs that assessed the effectiveness of the following treatments as a monotherapy or in combination as the first-line treatment: tamoxifen, anastrozole, letrozole, exemestane, fulvestrant, palbociclib, and ribociclib. The results were presented with pooled odds ratio or hazard ratio (HR), and 95% credible interval (CrI). The primary outcomes were objective response rate (ORR) and progression-free survival/time to progression. RESULTS: A total of 16 eligible articles (14 RCTs) involving 6,602 patients treated with 10 different first-line endocrine therapies were assessed in our network meta-analysis. Palbociclib plus letrozole was superior to anastrozole, letrozole, exemestane, fulvestrant 500 mg, and anastrozole plus fulvestrant (loading dose) (HR=0.44, 95% CrI: 0.33-0.58; HR=0.56, 95% CrI: 0.45-0.68; HR=0.45, 95% CrI: 0.32-0.61; HR=0.58, 95% CrI: 0.42-0.81; HR=0.50, 95% CrI: 0.37-0.68; respectively). However, there is no significant advantage compared with ribociclib plus letrozole (HR=1.00, 95% CrI: 0.72-1.39). In terms of ORR, ribociclib plus letrozole is more effective than palbociclib plus letrozole (odds ratio=1.30, 95% CrI: 0.83-2.02). CONCLUSION: Palbociclib plus letrozole and ribociclib plus letrozole might be the optimal first-line endocrine therapeutic choices for hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer due to a longer progression-free survival/time to progression and a more efficacious ORR.
RESUMO
BACKGROUND: The clinicopathological and prognostic values of the cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) in ovarian cancer (OC) remain unknown. The aim of our meta-analysis was to evaluate ALDH1's association with clinicopathological characteristics and its prognostic significance in patients with OC. MATERIALS AND METHODS: PubMed, Embase, and China Biology Medicine were systematically searched for eligible studies (up to October 2017). Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% CIs were used to evaluate the association of ALDH1 expression with clinicopathological features and survival outcomes. RESULTS: A total of 17 papers (18 studies) that included 2,531 patients with OC were analyzed. The results showed a significant association between increasing ALDH1 expression and International Federation of Gynecology and Obstetrics stage (OR 2.02, 95% CI 1.16-3.52), lymph node metastasis (OR 1.91, 95% CI 1.01-3.61), and distant metastasis (OR 5.43, 95% CI 1.44-20.42) in OC. However, no significant correlation was found between increasing ALDH1 expression and age (OR 0.90, 95% CI 0.25-3.28), tumor size (OR 1.13, 95% CI 0.75-1.71), tumor location (OR 0.69, 95% CI 0.22-2.13), ascite status (OR 0.74, 95% CI 0.49-1.11), resistance status (OR 0.70, 95% CI 0.14-3.51), or clinicopathological type (OR 1.14, 95% CI 0.69-1.86). Moreover, a high ALDH1 expression was significantly associated with overall survival (HR 1.56, 95% CI 1.21-2.02) but not with disease-free survival (HR 1.38, 95% CI 0.99-1.93). CONCLUSION: The meta-analysis indicates that increasing ALDH1 predicts poor prognosis and clinicopathological characteristics in OC. Future studies are needed to explore tailored treatments that directly target ALDH1 for the improvement of survival in OC.
