Research table: CDK4/6 inhibitors for metastatic breast cancer treatment

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: CDK4/6 inhibitors are drugs that target enzymes called CDK4 and CDK6. These enzymes are important in cell division. CDK4/6 inhibitors are designed to interrupt the growth of cancer cells.  

The CDK4/6 inhibitors used to treat metastatic breast cancer are:

• Abemaciclib (Verzenio)
• Palbociclib (Ibrance)
• Ribociclib (Kisqali)

These drugs are used in combination with hormone therapy to treat hormone receptor-positive, HER2-negative metastatic breast cancers. Abemaciclib alone may also be used to treat these cancers.

Compared to treatment with hormone therapy alone, hormone therapy plus a CDK4/6 inhibitor may give people more time before the cancer worsens [1-11].

Learn more about CDK4/6 inhibitors (including side effects) and metastatic breast cancer treatment.

Learn about CDK4/6 inhibitors and early breast cancer treatment.

Study selection criteria: Randomized clinical trials with 100 or more participants with hormone receptor-positive, HER2-negative metastatic breast cancer, and pooled analyses.  

Study	Study Population (number of participants)	Drug(s) Used	Overall Response Rate-Percent who Responded to Treatment (95% CI)	Overall Survival (95% CI)
Randomized clinical trials
MONALEESA-3 [1-2]	726	Ribociclib with hormone therapy (fulvestrant)	32% (28%-37%)*	Overall survival at 5 years: 46% (40%-52%)*,†
		Hormone therapy alone (fulvestrant)	22% (16%-27%)*	Overall survival at 5 years: 31% (23%-40%)*,†
MONARCH 2 [3]	669‡	Abemaciclib with hormone therapy (fulvestrant)	48% (43%-54%)*
		Hormone therapy alone (fulvestrant)	21% (15%-28%)*
MONALEESA-2 [4-5]	668	Ribociclib with hormone therapy (letrozole)	41% (35%-46%)*	Overall survival at 5 years: 52% (47%-58%)*,§
		Hormone therapy alone (letrozole)	28% (23%-32%)*	Overall survival at 5 years: 44% (38%-49%)*,§
MONALEESA-7 [6-7]	672¶	Ribociclib with hormone therapy (goserelin plus tamoxifen, letrozole or anastrozole)	41% (36%-46%)*	Overall survival at 3½ years: 70% (64%-76%)*
		Hormone therapy alone (goserelin plus tamoxifen, letrozole or anastrozole)	30% (25%-35%)*	Overall survival at 3½ years: 46% (32%-59%)*
PALOMA-2 [8-9]	666	Palbociclib with hormone therapy (letrozole)	42% (38%-47%)	Overall survival at 7½ years: 61% NS
		Hormone therapy alone (letrozole)	35% (28%-41%)	Overall survival at 7½ years: 59% NS
PALOMA-3 [10-11]	521	Palbociclib with hormone therapy (fulvestrant with or without goserelin)	25% (20%-30%)*	Overall survival at 5 years: 23% (19%-28%)*
		Hormone therapy alone (fulvestrant with or without goserelin)	11% (6%-17%)*	Overall survival at 5 years: 17% (11%-23%)*
MONARCH 3 [12]	493	Abemaciclib with hormone therapy (letrozole)	48% (43%-54%)*
		Hormone therapy alone (letrozole)	35% (27%-42%)*
PALOMA-4 [13]	340††	Palbociclib with hormone therapy (letrozole)	37% (30%-45%)
		Hormone therapy alone (letrozole)	32% (25%-39%)
RIGHT Choice [14]	222¶	Ribociclib with hormone therapy (letrozole plus goserelin or anastrozole plus goserelin)	66% (56%-75%)	Overall survival at 2½ years: 67% NS
		Chemotherapy (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine)	62% (52%-71%)	Overall survival at 2½ years: 65% NS
PATHWAY study [15]	184††	Palbociclib plus hormone therapy (tamoxifen with or without goserelin)	44% (34%-55%)
		Hormone therapy alone (tamoxifen with or without goserelin)	28% (19%-38%)
Pooled analyses
Gao et al. [16]	4,200 (7 studies)	Abemaciclib, palbociclib or ribociclib plus hormone therapy (anastrozole, fulvestrant or letrozole, all with or without goserelin)	37%
		Hormone therapy alone (anastrozole, fulvestrant or letrozole, all with or without goserelin)	25%
Howie et al. [17]	1,827 (3 studies)	Abemaciclib, palbociclib or ribociclib plus hormone therapy (letrozole)	Women younger than 70: 43% Women 70 and older: 43%
		Hormone therapy alone (letrozole)	Women younger than 70: 30% Women 70 and older: 31%

NS = No statistically significant difference between the 2 treatment groups

* Statistically significant difference between the 2 treatment groups

† Overall survival at 4 years was 54% (49%-58%) for women treated with ribociclib plus hormone therapy, and 45% (38%-51%) for women treated with hormone therapy alone

‡ All participants had past treatment with hormone therapy for metastatic breast cancer

§ Overall survival at 6 years was 44% (39%-50%) for women treated with ribociclib plus hormone therapy, and 32% (27%-37%) for women treated with hormone therapy alone

¶ All participants were premenopausal

** Median survival was 35 months in the women treated with palbociclib plus hormone therapy, and 28 months in the women treated with hormone therapy alone

†† All participants were Asian women living in Asia

References

1. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 36(24):2465-2472, 2018.
2. Slamon DJ, Neven P, Chia S, et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 32(8):1015-1024, 2021.
3. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 35(25):2875-2884, 2017.
4. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 375(18):1738-1748, 2016.
5. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med. 386(10):942-950, 2022.
6. Tripathy D, Im SA, Colleoni M. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 19(7):904-15, 2018.
7. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 381(4):307-316, 2019.
8. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 375(20):1925-1936, 2016.
9. Slamon DJ, Diéras V, Rugo HS, et al. Overall survival with palbociclib plus letrozole in advanced breast cancer. J Clin Oncol. 42(9):994-1000, 2024.
10. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 17(4):425-39, 2016.
11. Cristofanilli M, Rugo HS, Im SA, et al. Overall survival with palbociclib and fulvestrant in women with HR+/HER2- ABC: updated exploratory analyses of PALOMA-3, a double-blind, phase III randomized study. Clin Cancer Res. 28(16):3433-3442, 2022.
12. Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 35(32):3638-3646, 2017.
13. Xu B, Hu X, Li W, et al. Palbociclib plus letrozole versus placebo plus letrozole in Asian postmenopausal women with oestrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: primary results from PALOMA-4. Eur J Cancer. 175:236-245, 2022.
14. Lu YS, Mahidin EIBM, Azim H, et al. Final results of RIGHT Choice: Ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol. 42(23):2812-2821, 2024.
15. Noguchi E, Yamanaka T, Mukai H, et al. A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive/HER2-negative advanced breast cancer. NPJ Breast Cancer. 10(1):76, 2024.
16. Gao JJ, Cheng J, Bloomquist E, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: a US Food and Drug Administration pooled analysis. Lancet Oncol. 21(2):250-260, 2020.
17. Howie LJ, Singh H, Bloomquist E, et al. Outcomes of older women with hormone receptor-positive, human epidermal growth factor receptor-negative metastatic breast cancer treated with a CDK4/6 inhibitor and an aromatase inhibitor: an FDA pooled analysis. J Clin Oncol. 37(36):3475-3483, 2019. 

Updated 09/03/24