Should All Patients With HR-Positive HER2-Negative Metastatic Breast Cancer Receive CDK 4/6 Inhibitor As First-Line Based Therapy? A Network Meta-Analysis of Data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT Trials

Rossi, Valentina; Berchialla, Paola; Giannarelli, Diana; Nisticò, Cecilia; Ferretti, Gianluigi; Gasparro, Simona; Russillo, Michelangelo; Catania, Giovanna; Vigna, Leonardo; Mancusi, Rossella Letizia; Bria, Emilio; Montemurro, Filippo; Cognetti, Francesco; Fabi, Alessandra

doi:10.3390/cancers11111661

Cited by 53 publications

(46 citation statements)

References 37 publications

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“…52 Recent studies have also shown that CDK4/6 inhibitors have similar efficacy when combined with an AI in the first-line treatment of ER+ metastatic BC and are superior to monotherapy with FUL or AI, regardless of tumor characteristics. 12 These findings confirm that CDK4/6 inhibitors improve survival outcomes for ER+ BC patients when incorporated with AI in both the first and last lines. 47…”

Section: Cdk4/6 Inhibitorssupporting

confidence: 68%

“…The use of these inhibitors in combination with AI as first-line therapy or with FUL as second-line therapy in ER+/HER2-metastatic BC has shown improved progression-free survival in Phase III trials. 12,44,45 However, abemaciclib is the only inhibitor among the three CDK4/6 inhibitors that has received FDA approval as monotherapy in ER+/HER2-metastatic BC, indicating its high potential as a single agent. 46,47 Several phase III trials, such as the PALOMA-3 trial (FUL + palbociclib/placebo), 48 the MONARCH-2 trial (FUL + abemaciclib/placebo), 44 and the MONALEESA-3 trial (FUL with or without ribociclib), 49 have demonstrated the efficacy of the combination of FUL and CDK4/6 inhibitors.…”

Section: Cdk4/6 Inhibitorsmentioning

confidence: 99%

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<p>Resistance and Overcoming Resistance in Breast Cancer</p>

Luque-Bolivar¹,

Pérez-Mora²,

Villegas³

et al. 2020

BCTT

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The incidence and mortality of breast cancer (BC) have increased in recent years, and BC is the main cause of cancer-related death in women worldwide. One of the most significant clinical problems in the treatment of patients with BC is the development of therapeutic resistance. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. The therapeutic decision for the management of patients with BC is based not only on the assessment of prognostic factors but also on the evaluation of clinical and pathological parameters. Although this has been a successful approach, some patients relapse and/or eventually develop resistance to treatment. This review is focused on recent studies on the possible biological and molecular mechanisms involved in both response and resistance to treatment in BC. Additionally, emerging treatments that seek to overcome resistance and reduce side effects are also described. A greater understanding of the mechanisms of action of treatments used in BC might contribute not only to the enhancement of our understanding of the mechanisms involved in the development of resistance but also to the optimization of the existing treatment regimens.

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Section: Cdk4/6 Inhibitorssupporting

confidence: 68%

Section: Cdk4/6 Inhibitorsmentioning

confidence: 99%

<p>Resistance and Overcoming Resistance in Breast Cancer</p>

Luque-Bolivar¹,

Pérez-Mora²,

Villegas³

et al. 2020

BCTT

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show abstract

“…Our study included a large number of treatment options for hormone receptor-positive/HER2-negative advanced breast cancer, and involved subgroup analysis based on the status of PIK3CA mutation, ET resistance, and visceral metastasis, which no previous study has done [ 16 ]. However, there are still many limitations in this network meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, PALOMA-3 and MONARCH-2 showed that fulvestrant combined with CDK4/6 inhibitors was associated with longer PFS in ET-resistant patients [ 14 15 ]. Some articles indirectly compared the efficacy and toxicity among three different CDK4/6 inhibitors in the ﬁrst-line treatment, and they appeared to have a similar benefit without significant difference [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Network Meta-Analysis

Liu

Sun

et al. 2020

J Breast Cancer

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We aimed to explore what kind of endocrine treatments are optimal for hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

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“…In the context of metastatic breast cancer, the Special Issue contains two pieces of work focusing on important new targeted therapies currently licensed for clinical use, CDK4/6 inhibitors and anti-HER2 therapies. Rossi et al carried out a network meta-analysis comparing the combination use of individual CDK4/6 inhibitors with fulvestrant or an aromatase inhibitor [13]. They found that CDK4/6 inhibitors have similar efficacy when combined with an aromatase inhibitor in the first-line treatment of hormone receptor positive disease, and are superior to either endocrine agent as monotherapy, regardless of any other patient or tumour characteristics.…”

mentioning

confidence: 99%