| Consensus Statement | Quality of Evidence | Strength of Rec. | Key Ref |
|---|---|---|---|
| 1. CDK4/6 inhibitors combined with endocrine treatment(ET) are advised for first line treatment of HR–positive, HER2–negative MBC, including those with clinically aggressive disease,ͣ regardless of primary or secondary resistance of ET.ᵇ In the case of premenopausal patients, ovarian function suppression is recommended. | I | A | 1-6 |
| 2. For patients who did not relapse on an aromatase inhibitor (AI), or did not recurrence within 12 months of stopping adjuvant AI, a CDK4/6 inhibitor in combination with an AI is advised. Otherwise, SERDᶜ combined with a CDK4/6 inhibitor is considered. | I | A | 7-9 |
| 3. For patients who relapse on adjuvant ET or within 12 months after completing adjuvant treatment, in the presence of a PIK3CA mutation, a combination of inavolisib+palbociclib+fulvestrant is recommended. | I | A | 10-11 |
| 4. For patients on first-line CDK4/6 inhibitor plus AI therapy, substitution of the AI with camizestrant upon ESR1 mutation detection by liquid biopsy may be appropriate before disease progression.ᵈ | I | B | 12 |
| 5. Delayed combination of CDK4/6 inhibitor to second line treatment is acceptable.ͤ | I | B | 13-14 |
| 6. If recurrence develops at least one year after the completion of adjuvant CDK4/6 inhibitor treatment, the re-introduction of a CDK4/6 inhibitor could be considered. | III | B | 15 |
- Definition of aggressive ABC: symptomatic visceral metastases, rapid disease progression or impending visceral compromise, marked non–visceral disease but with total bilirubin <1.5 ULN.
- Ribociclib and Abemaciclib have shown OS benefit in phase 3 randomized controlled trial.
- Imlunestrant (FDA-approved as monotherapy for ESR1 mutation) or Fulvestrant
- At least 6 months of treatment with AI+CDK 4/6 inhibitor and no evidence of disease progression
- ET alone is acceptable for patients with comorbidities or a poor performance status. Palbociclib may be safer for older patients.
References
- Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925-1936.
- Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-1748.
- Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646.
- Lu YS, Im SA, Colleoni M, et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7. Clin Cancer Res. 2022.
- Yen-Shen Lu, et al. Primary results from the randomized Phase III RIGHT Choice trial… Cancer Res 2023;83(5 Suppl):Abstract nr GS1-10.
- Klijn, J G et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone… J Clin Oncol. 2001.
- Dai, Qiuying et al. Efficacy and safety of CDK4/6 inhibitors combined with endocrine therapy… Annals of palliative medicine. 2022.
- Llombart-Cussac A, et al. PARSIFAL: a randomized, multicenter, open-label, phase II trial… J Clin Oncol. 2020.
- Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. N Engl J Med. 2025.
- Turner NC, Im SA, Saura C, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2024.
- Jhaveri KL, Im SA, Saura C, et al. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2025.
- Bidard FC, Mayer EL, Park YH, et al. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. N Engl J Med. 2025.
- Rugo, Hope S et al. Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer… European journal of cancer. 2018.
- van Ommen-Nijhof, A et al. Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer – the SONIA study. BMC cancer. 2018.
- Bidard FC, Michiels S, et al. “Exponential tumor kinetics data support estrogen receptor degradation” Versus Standard Endocrine Therapy… EMERALD Trial. J Clin Oncol. 2022.