The Who, What, Where, When and Sometimes, Why.

CDK4/6 Inhibitors for Treatment of Metastatic Breast Cancer

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 a class of 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 currently used to treat metastatic breast cancer are abemaciclib (Verzenio), palbociclib (Ibrance) and 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.

CDK4/6 inhibitors may increase progression-free survival (give people more time before the cancer spreads) [1-11].

Learn more about CDK4/6 inhibitors, including their side effects.

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

MONARCH 2 [2]

669*

Abemaciclib with
hormone therapy
(fulvestrant)

 48%
(43-54%)†

 
  

 Hormone therapy alone
(fulvestrant)

21%
(15-28%)†

 

MONALEESA-2 [3]

668

  Ribociclib with
hormone therapy
(letrozole)

41%
(35-46%)†

 

 

 

 Hormone therapy alone
(letrozole)

28%
(23-32%)†

 

MONALEESA-7 [4-5]

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 [6]

666

Palbociclib with
hormone therapy
(letrozole)

42%
(38-47%)

 
  

Hormone therapy alone
(letrozole)

35%
(28-41%)

 

PALOMA-3 [7-8] 

521

Palbociclib with
hormone therapy
(fulvestrant with or without goserelin)

25%
(20-30%)†

Median overall survival:
NS§

  

Hormone therapy alone
(fulvestrant with or without goserelin)

11%
(6-17%)†

Median overall survival:
NS§

MONARCH 3 [9]

493

Abemaciclib with
hormone therapy
(letrozole)

48%
(43-54%)†

 
  

Hormone therapy alone
(letrozole)

35%
(27-42%)†

 

MONALEESA-3 [10-11]

484

Ribociclib with
hormone therapy
(fulvestrant)

32%
(28-37%)†

Overall survival at 3½ years:
58%
(52-63%)†

  

Hormone therapy alone
(fulvestrant)

22%
(16-27%)†

Overall survival at 3½ years:
46%
(37-55%)†

Pooled analyses

Gao et al. [12]

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%

NS = No statistically significant difference between the 2 treatment groups

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

† Statistically significant difference between the 2 treatment groups

‡ All participants were premenopausal

§ Median survival was 35 months in the women treated with palbociclib plus hormone therapy versus 28 months in the women treated with hormone therapy alone

References

  1. Turner NC, Ro J, André F, et al. for the PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 373(3):209-19, 2015.
  2. 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.
  3. 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.
  4. 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. 
  5. 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.
  6. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 375(20):1925-1936, 2016.
  7. 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.
  8. Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med. 379(20):1926-1936, 2018.
  9. 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. 
  10. 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.
  11. Slamon DJ, Neven P, Chia S, et al. Overall survival with ribociclib plus fulvestrant in advanced breast cancer. N Engl J Med. 2019 Dec 11 [Epub ahead of print].
  12. 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. 2019 Dec 16 [Epub ahead of print]. 

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