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Review
. 2023 Jun 2;30(6):5425-5447.
doi: 10.3390/curroncol30060411.

HR+/HER2- Advanced Breast Cancer Treatment in the First-Line Setting: Expert Review

Katarzyna J Jerzak  1 , Nathaniel Bouganim  2 , Christine Brezden-Masley  3 , Scott Edwards  4 , Karen Gelmon  5 , Jan-Willem Henning  6 , John F Hilton  7 , Sandeep Sehdev  7
Affiliations
Review

HR+/HER2- Advanced Breast Cancer Treatment in the First-Line Setting: Expert Review

Katarzyna J Jerzak et al. Curr Oncol. .

Abstract

The approval of CDK4/6 inhibitors has dramatically improved care for the treatment of HR+/HER2- advanced breast cancer, but navigating the rapidly-expanding treatment evidence base is challenging. In this narrative review, we provide best-practice recommendations for the first-line treatment of HR+/HER2- advanced breast cancer in Canada based on relevant literature, clinical guidelines, and our own clinical experience. Due to statistically significant improvements in overall survival and progression-free survival, ribociclib + aromatase inhibitor is our preferred first-line treatment for de novo advanced disease or relapse ≥12 months after completion of adjuvant endocrine therapy and ribociclib or abemaciclib + fulvestrant is our preferred first-line treatment for patients experiencing early relapse. Abemaciclib or palbociclib may be used when alternatives to ribociclib are needed, and endocrine therapy can be used alone in the case of contraindication to CDK4/6 inhibitors or limited life expectancy. Considerations for special populations-including frail and fit elderly patients, as well as those with visceral disease, brain metastases, and oligometastatic disease-are also explored. For monitoring, we recommend an approach across CDK4/6 inhibitors. For mutational testing, we recommend routinely performing ER/PR/HER2 testing to confirm the subtype of advanced disease at the time of progression and to consider ESR1 and PIK3CA testing for select patients. Where possible, engage a multidisciplinary care team to apply evidence in a patient-centric manner.

Keywords: CDK4/6 inhibitors; HR+/HER2–; advanced breast cancer; mutational testing; treatment considerations.

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Conflict of interest statement

K.J.J.: Advisory boards—Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Gilead Sciences, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Seagen, Novartis, Viatris. Speaker honoraria—Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Gilead Sciences, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Seagen, Novartis, Viatris. Grants/research support—AstraZeneca, Eli Lilly, Seagen; N.B.: Honoraria—Merck, Novartis, Astra Zeneca; C.B.-M.: Advisory boards/consultancy and speaker honoraria*—Astra Zeneca, Agendia, BMS, Knight, Merck, Lilly*, Novartis*, Pfizer*, Roche, Seagen, Taiho, Sanofi, Mylan, Gilead; S.E.: Apobiologix, Astellas, Astra Zeneca, Bayer, Eli Lilly, Gilead; K.G.: Advisory boards—Astra Zeneca, Merck, Gilead, Seagan, Pfizer, Novartis, Lilly; J.-W.H.: Advisory boards and speaker honoraria—Astra Zeneca, Novartis, Pfizer, Gilead, Eli Lilly, Seagen, Merck; J.F.H.: TBD; S.S.: Advisory board and speaker honoraria—Astra Zeneca, Novartis.

Figures

Figure 1
Figure 1
Summary of PFS and OS outcomes from phase 3 first-line CDK4/6i + nonsteroidal AI trials (investigator analysis).
Figure 2
Figure 2
Summary of PFS and OS outcomes from phase 3 trials evaluating CDK4/6i + fulvestrant in HR+/HER2– advanced breast cancer.
Figure 3
Figure 3
Mutational testing at diagnosis of advanced/metastatic disease.
Figure 4
Figure 4
Incidence of most common adverse reactions as per product monograph in patients with advanced breast cancer receiving CDK4/6i + nonsteroidal AI.
Figure 5
Figure 5
Suggested monitoring approach for CDK4/6i.
Figure 6
Figure 6
Importance of different treatment characteristics in decisions for metastatic breast cancer patients (Canadian Breast Cancer Network).
Figure 7
Figure 7
Clinical verifications of prescriptions checklist tool for community pharmacists.
Figure 8
Figure 8
Summary of preferred treatment pathway for first-line HR+/HER2– advanced breast cancer.
Figure 9
Figure 9
Summary of preferred first-line treatments for HR+/HER2– advanced breast cancer.
See this image and copyright information in PMC

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