Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij borstkanker van arts-bioloog drs. Engelbert Valstar

6 april 2023: Bron: JAMA Oncol. Published online March 9, 2023. 

De aurora A-kinaseremmer alisertib  in combinatie met fulvestrant geeft geen extra voordeel in vergelijking met  Alisertib alleen bij patiënten met hormoonresistente gevorderde borstkanker. Bij beide groepen lag de respons met alleen alisertib en de combinatiegroep met fulvestrant op respectievelijk 19,6% en 20,0%. De resultaten van de progressievrije overleving waren ook vergelijkbaar tussen de twee armen na respectievelijk 5,6 maanden en 5,4 maanden. Uit de onderzoeksresultaten bleek wel dat in de groep die alleen alisertib als medicijn kreeg veelbelovende klinische activiteit werd waargenomen bij patiënten met hormoonresistente en cycline-afhankelijke kinase 4/6-remmer-resistente gemetastaseerde borstkanker. 

Hier de hoofdvraag en doel en resultaat van deze studie:
  • Vraag: Herstelt behandeling met alisertib de gevoeligheid voor fulvestrant en verbetert het de tumor objectieve response rates (ORR's) in vergelijking met alisertib monotherapie bij patiënten met hormoonresistente gemetastaseerde borstkanker?
  • Bevindingen: In deze gerandomiseerde klinische fase 2-studie met 91 patiënten met hormoonresistente, gemetastaseerde borstkanker die eerder waren behandeld met een cycline-afhankelijke kinase 4/6-remmer, werden de deelnemers gerandomiseerd ingedeeld om een behandeling met alleen alisertib of gecombineerd met fulvestrant te krijgen. De ORR werd niet significant verbeterd door de toevoeging van fulvestrant aan alisertib, met een ORR van ongeveer 20,0% voor beide groepen.
  • Betekenis: Uit de onderzoeksresultaten bleek dat hoewel alisertib de fulvestrantgevoeligheid niet herstelde en de ORR's niet verhoogde, veelbelovende klinische activiteit werd waargenomen met alisertib-monotherapie bij patiënten met hormoonresistente en cycline-afhankelijke kinase 4/6-remmer-resistente gemetastaseerde borstkanker.
Het volledige studierapport is gratis in te zien of te downloaden. Zie ook discussie aan het eind van het abstract met verwijzing naar andere studies in referentielijst. Klik daarvoor op de titel van het abstract:

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Abstract
Evaluation of Alisertib Alone or Combined With Fulvestrant in Patients With Endocrine-Resistant Advanced Breast Cancer
Key Points

Question  Does treatment with alisertib restore fulvestrant sensitivity and improve tumor objective response rates (ORRs) compared with alisertib monotherapy in patients with endocrine-resistant metastatic breast cancer?

Findings  In this phase 2 randomized clinical trial of 91 patients with endocrine-resistant, metastatic breast cancer who were previously treated with a cyclin-dependent kinase 4/6 inhibitor, participants were randomized to receive treatment with alisertib alone or combined with fulvestrant. The ORR was not significantly improved by the addition of fulvestrant to alisertib, with an ORR of approximately 20.0% for both regimens.

Meaning  The trial results found that while alisertib did not restore fulvestrant sensitivity and increase ORRs, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and cyclin-dependent kinase 4/6 inhibitor–resistant metastatic breast cancer.

Abstract

Importance  Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i–resistant MBC is unknown.

Objective  To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC.

Design, Setting, and Participants  This phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)–negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (<10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022.

Interventions  Alisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2).

Main Outcomes and Measures  Improvement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%.

Results  All 91 evaluable patients (mean age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]).

Conclusions and RelevanceThis randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i–resistant MBC. The overall safety profile was tolerable.

Trial Registration: ClinicalTrials.gov Identifier: NCT02860000  

Discussion

In this randomized phase 2 clinical trial, the clinical efficacy and safety of alisertib alone or combined with fulvestrant was evaluated in ERBB2 MBC. All patients received prior treatment with CDK 4/6i, and of those with ER+ MBC, all received prior fulvestrant. While the addition of fulvestrant to alisertib did not improve ORR, clinically meaningful antitumor activity was observed in both arms. Among those who received alisertib, this included a confirmed ORR of 19.6%, 24-week CBR of 41.3%, mPFS of 5.6 months, and median OS of 22.7 months.

These results confirm prior findings demonstrating the antitumor activity of alisertib in endocrine-resistant, ER+/ERBB2 MBC. They are comparable with those observed in prior trials with established effective agents. For example, in MONARCH-1, a phase 2 study of the CDK 4/6i abemaciclib in patients with ER+ MBC that was previously treated with ET and 2 or fewer prior lines of chemotherapy, the confirmed ORR was 19.7% (95% CI, 13.3%-27.5%), 6-month CBR was 42.4%, mPFS was 6.0 months, and median OS was 17.7 months.23 These findings led to the US Food and Drug Administration approval of abemaciclib as monotherapy.

While caution must be applied when conducting cross-trial comparisons, to our knowledge, there is a paucity of clinical data regarding the efficacy of approved or investigational therapies following CDK 4/6i progression. Evaluating the current study results in this context may help to understand the potential value of alisertib in the evolving landscape of endocrine-resistant and CDK 4/6i–resistant MBC. Notably, single-agent ET has limited efficacy in this setting, as evidenced by the phase 2 VERONICA trial (n = 101) in which mPFS to fulvestrant was 1.94 months (95% CI, 1.84-3.55).24 In the phase 3 EMERALD trial, the oral selective ER degrader elacestrant was associated with a significantly improved mPFS compared with standard ET (fulvestrant or AI); however, mPFS was only 2.8 months.17

In the BYLieve trial, a single-arm study of alpelisib with fulvestrant in patients with CDK 4/6i–resistant, PIK3CA-variant, ER+ MBC, those with measurable disease (n = 100) had an ORR (calculated as best overall response) of 21% (95% CI, 14%-30%) and a 24-week CBR of 42% (95% CI, 35%-52%).25 In the overall cohort (n = 121), including those with the more clinically favorable nonmeasurable disease, mPFS was 7.3 months; (95% CI, 5.6-8.3) and mOS was 17.3 months (95% CI, 17.2-20.7). The duration of follow-up in BYLieve was limited, and thus the OS results may be immature. Additionally, PIK3CA-variant, ER+/ERBB2 MBC is associated with shortened OS and resistance to chemotherapy compared with those with PIK3CA wild-type disease.26 While alisertib was associated with comparable clinical activity observed in the BYLieve trial, its efficacy in the setting of PIK3CA-variant disease is unknown and will be explored in subsequent correlative studies.

The phase 3 TROPICS-02 trial (n = 543) included patients with endocrine-resistant and CDK 4/6i–resistant MBC and reported an improvement in mPFS with the antibody drug conjugate sacituzumab govitecan (5.5 months; 95% CI, 4.2-7.0) compared with single-agent chemotherapy of the physician’s choice (4.0 months; 95% CI, 3.1-4.4).27 In the phase 3 DESTINY B-04 trial, among those in the analytic cohort with hormone receptor–positive/ERBB2 (HER2)–low disease (n = 494), all patients were endocrine resistant, and 70.4% received prior treatment with CDK 4/6i. An improvement in mPFS was reported with the antibody drug conjugate trastuzumab deruxtecan compared with single-agent chemotherapy of the physician’s choice (10.1 vs 5.4 months; HR, 0.51, 95% CI, 0.4-0.64).28 Thus, the mPFS and other clinical outcomes associated with alisertib are similar to those observed in comparable patients treated with single-agent chemotherapy or sacituzumab govitecan.

An increased rate of investigational therapy discontinuation for reasons other than PD was observed in this trial among those receiving combination fulvestrant and alisertib. This was unexpected given the lack of overlapping toxic effects and favorable safety profile observed in our prior phase 1 trial of combination therapy.14 There were only minor differences in the most common AEs between arms. While there were more grade 3 fatigue and thromboembolic events in arm 2, they did not lead to treatment discontinuation. More patients in arm 2 than arm 1 received prior everolimus (57.8% vs 37.0%) and chemotherapy (68.9% vs 47.8%) for MBC. Thus, it is feasible that heavier pretreatment with other targeted and cytotoxic agents may have decreased tolerance to the investigational therapy. This is further strengthened by the observation that all 17 arm 1 patients who crossed over to arm 2 discontinued combination therapy due to PD, not treatment intolerance.

Given the clinical efficacy and safety results observed in TBCRC 041, continued clinical development of alisertib is warranted and planned. Further supporting this is the observation of clinical activity among those who received prior everolimus. If the clinical outcomes observed in this study were confirmed in a subsequent registration trial, alisertib may provide a new treatment option for endocrine-resistant disease to a broader cohort of patients given that alpelisib is only available for PIK3CA-variant MBC, which is present only in 25% to 40% of ER+/ERBB2 MBC.25,29

The correlative studies indicated that high AURKA registration tumor expression was associated with poor clinical outcomes, which was consistent with prior studies.9,30 Additional correlative studies are under way to evaluate the role of PIK3CA variant status and assess whether pharmacodynamic-induced changes in ERα, total and phosphorylated AURKA, and other stemness biomarkers that are associated with clinical benefit from alisertib.

While alisertib did not restore sensitivity to fulvestrant as preclinical studies5,6 conducted before the CDK 4/6i era had suggested, it is feasible the hypothesis was not fairly tested given that accumulating clinical data demonstrate minimal antitumor activity of endocrine monotherapy following CDK 4/6i progression17,24 and the fact that the entire cohort received prior CDK 4/6i therapy. Furthermore, the role of continued ER blockade in combination with targeted therapies after CDK 4/6i progression is unclear.

Limitations

Limitations to this trial include a higher percentage of women with obesity who were assigned to arm 1, while a higher percentage of women who had prior exposure to chemotherapy and/or everolimus were assigned to arm 2. Obesity, with its associated comorbidities, as well as prior exposure to chemotherapy, may have negatively affected tolerability to alisertib and the ability to continue receiving treatment. Additionally, the study cohort was confined to postmenopausal women, and participation of those of racial and ethnic minority groups was suboptimal, thus limiting generalizability. Finally, the sample size for the correlative studies was small, which limits interpretation.

Conclusions

This phase 2 randomized clinical trial found that alisertib is among the first investigational targeted therapies demonstrating promising clinical activity and a tolerable safety profile in the setting of endocrine and CDK 4/6i–resistant MBC.

Article Information

Accepted for Publication: November 23, 2022.

Published Online: March 9, 2023. doi:10.1001/jamaoncol.2022.7949

Corresponding Author: Tufia Haddad, MD, Department of Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (haddad.tufia@mayo.edu).

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Haddad TC et al. JAMA Oncology.

Author Contributions: Drs Haddad and Suman had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Haddad, Suman, D’Assoro, I. Mayer, Keyomarsi, Liu, Ingle, Goetz.

Acquisition, analysis, or interpretation of data: Haddad, Suman, Carter, Giridhar, McMenomy, Santo, E. Mayer, Karuturi Sri, Morikawa, Marcom, Isaacs, Oh, Clark, I. Mayer, Hobday, Peethambaram, O’Sullivan, Leon-Ferre, Liu, Ingle, Goetz.

Drafting of the manuscript: Haddad, Suman, D’Assoro, Santo, Clark, Peethambaram, O’Sullivan, Goetz.

Critical revision of the manuscript for important intellectual content: Haddad, Suman, Carter, Giridhar, McMenomy, E. Mayer, Karuturi Sri, Morikawa, Marcom, Isaacs, Oh, Clark, I. Mayer, Keyomarsi, Hobday, Leon-Ferre, Liu, Ingle, Goetz.

Statistical analysis: Suman, Santo.

Obtained funding: Haddad.

Administrative, technical, or material support: D’Assoro, McMenomy, Morikawa, Isaacs, Clark, Keyomarsi, O’Sullivan, Leon-Ferre, Liu, Goetz.

Supervision: Haddad, Peethambaram, O’Sullivan, Goetz.

Other: Carter, Clark.

Conflict of Interest Disclosures: Dr Haddad reported grant funding from Takeda Oncology for the conduct of the clinical trial that was associated with this manuscript but she did not receive any personal funding, as all dollars went to the Mayo Clinic. Dr E. Mayer reported consulting fees from Lilly, Novartis, AstraZeneca, and Gilead outside the submitted work. Dr Karuturi Sri reported personal fees from Lilly and Gilead during the conduct of the study. Dr Morikawa reported research support from Takeda and Eisai during the conduct of the study as well as personal fees from Seagen, Lilly, and Eisai, reviewer fees from Taiho, grants from Pfizer, nonfinancial support from Tempus, and research support from MTEM, Dantari, Suzhou Zanrong Pharma limited (formerly Zion), Merck, Roche, Puma, and Novartis outside the submitted work. Dr Isaacs reported personal fees from Genentech, Puma Seattle Genetics, AstraZeneca, Novartis, Pfizer, Sanofi, Gilead, ION, Wolters Kluwer, McGraw Hill, and SideOut Foundation as well as grants from GSK and Pfizer outside the submitted work. Dr Clark reported grants from Novartis and Lilly, steering committee service for Novartis Scientific, and honoraria from Siemens during the conduct of the study. Dr I. Mayer reported personal fees from AstraZeneca, Genentech, Lilly, Puma, Novartis, GSK, Polyphor, Macrogenics, SeaGen, AbbVie, Immunomedics, Cyclacel, Blueprint, and Pfizer as well as employment with AstraZeneca outside the submitted work. Dr Keyomarsi reported research funding outside the submitted work from Repare Therapeutics (institutional), Apeiron Biologics (institutional), Blueprint Medicines (institutional), Schrodinger Inc (institutional), the National Institutes of Health (NIH), and National Cancer Institute R01 grants CA255960 and CA223772 and CPRIT multiinvestigator grant RP180712. Dr O’Sullivan reported research support from Lilly, Seagen, Minnemarita Therapeutics, Biovica, nference, ACCRU, Bavarian Nordic, Sermonix Pharmaceuticals, and AstraZeneca. Dr Leon-Ferre reported personal fees from Gilead Sciences, Lyell Immunopharma, and AstraZeneca outside the submitted work. Dr Liu reported research support from Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, and Tesaro; employment with Natera after the submitted work was completed; and board service for AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, and Syndax outside the submitted work. Dr Ingle reported grants from the Translational Breast Cancer Research Consortium and Prospect Creek Foundation during the conduct of the study. Dr Goetz reported grants from Takeda during the conduct of the study as well as personal fees from Genomic Health, AstraZeneca, Biovica, Eli Lilly, Novartis, Context Pharm, Eagle Pharm, ARC Therapeutics, Blueprint, Biotheranostics, Sanofi Genzyme, Research to Practice, Clinical Education Alliance, Medscape, MJH Life Sciences, and Total Health and grants from AstraZeneca, Eli Lilly, and Pfizer outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by Takeda Oncology, TBCRC foundational partner support from the Breast Cancer Research Foundation and Susan G. Komen, NIH grants K12 CA90628 (Dr Haddad) and R01 CA214893 (Drs Haddad and D’Assoro), Prospect Creek Foundation (Drs Haddad and D’Assoro), American Association for Cancer Research/American Society of Clinical Oncology Vail Workshop NIH grant R25CA068647 (Dr Haddad).

Role of the Funder/Sponsor: The funding entities had no role in the design and conduct of the investigator-initiated study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript; however, Takeda Oncology and the TBCRC Executive Committee did approve the final draft of the manuscript.

Data Sharing Statement: See Supplement 3.

Meeting Presentation: This study was presented virtually at the 2020 Annual Meeting of the San Antonio Breast Cancer Symposium; December 8, 2020; San Antonio, Texas.

Additional Contributions: We thank all the patients who generously volunteered to participate in this study. We thank the TBCRC central office, as well as the investigators, research nurses, and study coordinators at each site, for their support of the patients and integrity with the research procedures. We thank Melissa Schardt, BS, for her administrative assistance preparing the manuscript, for which she did not receive any compensation.

 

References
1.
Osborne  CK, Schiff  R.  Mechanisms of endocrine resistance in breast cancer.   Annu Rev Med. 2011;62:233-247. doi:10.1146/annurev-med-070909-182917PubMedGoogle ScholarCrossref
2.
Kuukasjärvi  T, Kononen  J, Helin  H, Holli  K, Isola  J.  Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.   J Clin Oncol. 1996;14(9):2584-2589. doi:10.1200/JCO.1996.14.9.2584PubMedGoogle ScholarCrossref
3.
Gutierrez  MC, Detre  S, Johnston  S,  et al.  Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase.   J Clin Oncol. 2005;23(11):2469-2476. doi:10.1200/JCO.2005.01.172PubMedGoogle ScholarCrossref
4.
Lindström  LS, Karlsson  E, Wilking  UM,  et al.  Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression.   J Clin Oncol. 2012;30(21):2601-2608. doi:10.1200/JCO.2011.37.2482PubMedGoogle ScholarCrossref
5.
D’Assoro  AB, Liu  T, Quatraro  C,  et al.  The mitotic kinase Aurora–a promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα(+) breast cancer cells.   Oncogene. 2014;33(5):599-610. doi:10.1038/onc.2012.628PubMedGoogle ScholarCrossref
6.
Opyrchal  M, Salisbury  JL, Zhang  S,  et al.  Aurora-A mitotic kinase induces endocrine resistance through down-regulation of ERα expression in initially ERα+ breast cancer cells.   PLoS One. 2014;9(5):e96995. doi:10.1371/journal.pone.0096995PubMedGoogle ScholarCrossref
7.
Thrane  S, Pedersen  AM, Thomsen  MB,  et al.  A kinase inhibitor screen identifies Mcl-1 and Aurora kinase A as novel treatment targets in antiestrogen-resistant breast cancer cells.   Oncogene. 2015;34(32):4199-4210. doi:10.1038/onc.2014.351PubMedGoogle ScholarCrossref
8.
Hole  S, Pedersen  AM, Lykkesfeldt  AE, Yde  CW.  Aurora kinase A and B as new treatment targets in aromatase inhibitor-resistant breast cancer cells.   Breast Cancer Res Treat. 2015;149(3):715-726. doi:10.1007/s10549-015-3284-8PubMedGoogle ScholarCrossref
9.
Siggelkow  W, Boehm  D, Gebhard  S,  et al.  Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients.   BMC Cancer. 2012;12:562. doi:10.1186/1471-2407-12-562PubMedGoogle ScholarCrossref
10.
Friedberg  JW, Mahadevan  D, Cebula  E,  et al.  Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.   J Clin Oncol. 2014;32(1):44-50. doi:10.1200/JCO.2012.46.8793PubMedGoogle ScholarCrossref
11.
Dees  EC, Cohen  RB, von Mehren  M,  et al.  Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations.   Clin Cancer Res. 2012;18(17):4775-4784. doi:10.1158/1078-0432.CCR-12-0589PubMedGoogle ScholarCrossref
12.
D’Assoro  AB, Haddad  T, Galanis  E.  Aurora-A Kinase as a promising therapeutic target in cancer.   Front Oncol. 2016;5:295. doi:10.3389/fonc.2015.00295PubMedGoogle ScholarCrossref
13.
Melichar  B, Adenis  A, Lockhart  AC,  et al.  Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study.   Lancet Oncol. 2015;16(4):395-405. doi:10.1016/S1470-2045(15)70051-3PubMedGoogle ScholarCrossref
14.
Haddad  TC, D’Assoro  A, Suman  V,  et al.  Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer.   Breast Cancer Res Treat. 2018;168(3):639-647. doi:10.1007/s10549-017-4616-7PubMedGoogle ScholarCrossref
15.
Huck  JJ, Zhang  M, Mettetal  J,  et al.  Translational exposure-efficacy modeling to optimize the dose and schedule of taxanes combined with the investigational Aurora A kinase inhibitor MLN8237 (alisertib).   Mol Cancer Ther. 2014;13(9):2170-2183. doi:10.1158/1535-7163.MCT-14-0027PubMedGoogle ScholarCrossref
16.
Li  J, Huo  X, Zhao  F,  et al.  Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor–positive metastatic breast cancer: a systematic review and meta-analysis.   JAMA Netw Open. 2020;3(10):e2020312. doi:10.1001/jamanetworkopen.2020.20312
ArticlePubMedGoogle ScholarCrossref
17.
Bidard  FC, Kaklamani  VG, Neven  P,  et al.  Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: results from the randomized phase III EMERALD trial.   J Clin Oncol. 2022;40(28):3246-3256. doi:10.1200/JCO.22.00338PubMedGoogle ScholarCrossref
18.
Wander  SA, Cohen  O, Gong  X,  et al.  The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor–positive metastatic breast cancer.   Cancer Discov. 2020;10(8):1174-1193. doi:10.1158/2159-8290.CD-19-1390PubMedGoogle ScholarCrossref
19.
Elfgen  C, Bjelic-Radisic  V.  Targeted therapy in HR+ HER2− metastatic breast cancer: current clinical trials and their implications for CDK4/6 inhibitor therapy and beyond treatment options.   Cancers (Basel). 2021;13(23):5994. doi:10.3390/cancers13235994PubMedGoogle ScholarCrossref
20.
Pocock  SJ, Simon  R.  Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial.   Biometrics. 1975;31(1):103-115. doi:10.2307/2529712PubMedGoogle ScholarCrossref
21.
Cardoso  F, Senkus  E, Costa  A,  et al.  4th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 4).   Ann Oncol. 2018;29(8):1634-1657. doi:10.1093/annonc/mdy192PubMedGoogle ScholarCrossref
22.
Jung  SH.  Randomized phase II trials with a prospective control.   Stat Med. 2008;27(4):568-583. doi:10.1002/sim.2961PubMedGoogle ScholarCrossref
23.
Dickler  MN, Tolaney  SM, Rugo  HS,  et al.  MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2 metastatic breast cancer.   Clin Cancer Res. 2017;23(17):5218-5224. doi:10.1158/1078-0432.CCR-17-0754PubMedGoogle ScholarCrossref
24.
Lindeman  GJ, Bowen  R, Jerzak  KJ,  et al.  Results from VERONICA: a randomized, phase II study of second-/third-line venetoclax (VEN) plus fulvestrant (F) versus F alone in estrogen receptor (ER)-positive, HER2-negative, locally advanced, or metastatic breast cancer (LA/MBC).   J Clin Oncol. 2021;39(15):1. doi:10.1200/JCO.2021.39.15_suppl.1004Google ScholarCrossref
25.
Rugo  HS, Lerebours  F, Ciruelos  E,  et al.  Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study.   Lancet Oncol. 2021;22(4):489-498. doi:10.1016/S1470-2045(21)00034-6PubMedGoogle ScholarCrossref
26.
Mosele  F, Stefanovska  B, Lusque  A,  et al.  Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer.   Ann Oncol. 2020;31(3):377-386. doi:10.1016/j.annonc.2019.11.006PubMedGoogle ScholarCrossref
27.
Rugo  HS, Bardia  A, Marmé  F,  et al.  Primary results from TROPiCS-02: a randomized phase 3 study of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) in patients (pts) with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer.   J Clin Oncol. 2022;40(17)(suppl):LBA1001-LBA1001. doi:10.1200/JCO.2022.40.17_suppl.LBA1001Google ScholarCrossref
28.
Modi  S, Jacot  W, Yamashita  T,  et al; DESTINY-Breast04 Trial Investigators.  Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer.   N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690PubMedGoogle ScholarCrossref
29.
Kalinsky  K, Jacks  LM, Heguy  A,  et al.  PIK3CA mutation associates with improved outcome in breast cancer.   Clin Cancer Res. 2009;15(16):5049-5059. doi:10.1158/1078-0432.CCR-09-0632PubMedGoogle ScholarCrossref
30.
Xu  J, Wu  X, Zhou  WH,  et al.  Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer.   PLoS One. 2013;8(2):e56919. doi:10.1371/journal.pone.0056919PubMedGoogle ScholarCrossref

 







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