Abstract
Background: The optimal second-line therapy for hormone receptor-positive (HR+)/ human
epidermal growth factor receptor 2 negative (HER2−) advanced or metastatic breast cancer is yet to be
established. Therefore, we conducted a network meta-analysis (NMA) of marketed drugs to compare
their efficacy.
Methods: We searched the literature in PubMed, Embase, Web of Science databases, and the main
international conferences in the past 5 years to find phase III clinical trials on drugs available in the
market. Network meta-analysis of progression-free survival (PFS), overall survival (OS), and the objective
response rate (ORR) was performed using R software. The efficiency of treatment options was
compared using hazard ratios and 95% credibility intervals.
Results: Overall, 12 studies with 6120 patients were included in the analysis. In an indirect comparison
of the five regimens, cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) plus 500 mg fulvestrant
(Ful500) gave the best PFS results; palbociclib ranked first with a surface under the cumulative ranking
(SUCRA) of 94.99%, followed by mammalian target of rapamycin inhibitor (mTORi) plus everolimus
(SUCRA=73.07%), phosphoinositide 3-kinase inhibitor (PI3Ki) plus Ful500 (SUCRA=66.73%),
Ful500 alone (SUCRA=44.55%), and histone deacetylase inhibitor (HDACi) plus exemestane (SUCRA=
43.49%). However, no significant difference was found in the PFS rates of CDK4/6i, mTORi,
and PI3Ki. For OS, CDK4/6i plus Ful500 ranked first; the SUCRA of ribociclib, abemaciclib, and palbociclib
were 86.20%, 83.98%, and 78.52%, respectively. Alpelisib plus Ful500 (SUCRA=66.91%)
ranked second but was not statistically different from CDK4/6i. The mTORi plus everolimus group
had the best ORR (SUCRA=88.73%). In terms of safety, 81.56% of patients in the tucidinostat plus
exemestane regimen developed neutropenia, suggesting strong hematological toxicity; 13.40% of patients
developed grade 3-4 diarrhea after using abemaciclib plus Ful500.
Conclusion: For second-line endocrine therapy in HR+/HER2− advanced/metastatic breast cancer,
CDK4/6i is a better choice than mTORi, PI3Ki, HDACi, and Ful; it shows good PFS and OS outcomes
and a low probability for serious adverse events.
Graphical Abstract
[5]
Cardoso, F.; Paluch-Shimon, S.; Senkus, E.; Curigliano, G.; Aapro, M.S.; André, F.; Barrios, C.H.; Bergh, J.; Bhattacharyya, G.S.; Biganzoli, L.; Boyle, F.; Cardoso, M.J.; Carey, L.A.; Cortés, J.; El Saghir, N.S.; Elzayat, M.; Eniu, A.; Fallowfield, L.; Francis, P.A.; Gelmon, K.; Gligorov, J.; Haidinger, R.; Harbeck, N.; Hu, X.; Kaufman, B.; Kaur, R.; Kiely, B.E.; Kim, S.B.; Lin, N.U.; Mertz, S.A.; Neciosup, S.; Offersen, B.V.; Ohno, S.; Pagani, O.; Prat, A.; Penault-Llorca, F.; Rugo, H.S.; Sledge, G.W.; Thomssen, C.; Vorobiof, D.A.; Wiseman, T.; Xu, B.; Norton, L.; Costa, A.; Winer, E.P. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5).
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[
http://dx.doi.org/10.1016/j.annonc.2020.09.010] [PMID:
32979513]
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