Preusser M, De Mattos-Arruda L, Thill M, et al. CDK4/6 inhibitors in the treatment of patients with breast cancer: summary of a multidisciplinary round-table discussion. ESMO Open 2018;3:e000368. doi: 10.1136/esmoopen-2018-000368.
This article has been corrected since its first publication.
Table 2 (page 5), Table 3 (page 5) and Table 4 (page 6) have been updated as follows:
Table 2: Phase III trials with CDK4/6 inhibitors in HR-positive/HER2-negative MBC: median PFS and objective response rate (ORR).
| Trial | Line in the metastatic setting | Patients (n) | Treatment | HR for PFS | Median PFS, months | Objective response rate (ITT population) (%) |
| PALOMA-2 | 1L | 666 | Palbociclib + letrozole vs placebo + letrozole | 0.58 | 24.8 vs 14.5 | 42.1 vs 34.7 |
| PALOMA-3 | >1L | 521 | Palbociclib + fulvestrant vs placebo + fulvestrant | 0.46 | 9.5 vs 4.6 | 19 vs 8 |
| MONALEESA-2 | 1L | 668 | Ribociclib + letrozole vs placebo + letrozole | 0.56 | NR vs 14.7 | 40.7 vs 27.5 |
| MONARCH 3 | 1L | 493 | Abemaciclib + NSAI vs placebo + NSAI | 0.54 | NR vs 14.7 | 59 vs 44 |
| MONARCH 2 | 1L or 2L | 669 | Abemaciclib + fulvestrant vs placebo + fulvestrant | 0.55 | 16.4 vs 9.3 | 48.1 vs 21.3 |
Table 3:
Phase III trials with CDK4/6 in HR-positive/HER2-negative MBC: safety data
| Adverse event (AE) | PALOMA-2 | PALOMA-3 | MONALEESA-2 | MONARCH 3 | MONARCH 2 | ||||||||||
| Grade % | Grade % | Grade % | Grade % | Grade % | |||||||||||
| All | 3 | 4 | All | 3 | 4 | All | 3 | 4 | All | 3 | 4 | All | 3 | 4 | |
| Rash | 18 | 1 | – | NR | NR | NR | 17.1 | 0.6 | – | NR | NR | NR | 11.1 | 1.1 | 0 |
| Fatigue | 37 | 2 | – | 38 | 2 | – | 36.5 | 2.1 | 0.3 | 40.1 | 1.8 | – | 39.9 | 2.7 | – |
| Diarrhea | 26 | 1 | – | 19 | – | – | 35 | 1.2 | – | 81.3 | 9.5 | – | 86.4 | 13.4 | 0 |
| Nausea | 35 | <1 | – | 29 | – | – | 51.4 | 2.4 | – | 38.5 | 0.9 | – | 45.1 | 2.7 | – |
| Decreased appetite | 15 | 1 | – | 12.8 | 0.9 | – | 18.6 | 1.5 | – | 24.5 | 1.2 | – | 26.5 | 1.1 | 0 |
| Neutropenia | 80 | 56 | 10 | 78.8 | 53.3 | 8.7 | 74.3 | 49.7 | 9.6 | 41.3 | 19.6 | 1.5 | 46.0 | 23.6 | 2.9 |
| Anaemia | 24 | 5 | <1 | 26.1 | 2.6 | 0 | 18.6 | 0.9 | 0.3 | 28.4 | 5.8 | – | 29.0 | 7.0 | 0.2 |
| Thrombocytopenia | 16 | 1 | <1 | 19.4 | 1.7 | 0.6 | 9 | 0.6 | – | NR | NR | NR | 15.6 | 2.0 | 1.4 |
| Alopecia | 33 | – | – | 14.8 | – | – | 33.2 | – | – | 26.6 | – | – | 15.6 | – | – |
| QTcF Prolongation | – | – | 3.3 | – | – | ||||||||||
| Increased creatinine | – | – | – | 19 | 2.1 | – | 11.8 | 0.9 | 0 | ||||||
Table 4:
Phase III trials with CDK4/6 in HR-positive/HER2-negative MBC: inclusion criteria
| PALOMA-2 (%) | PALOMA-3 (%) | MONALEESA-2 (%) | MONARCH 3 (%) | MONARCH 2 (%) | ||||||
| Palbociclib + Letrozol | Placebo + Letrozol |
Palbociclib + Fulvestrant | Placebo + Fulvestrant | Ribociclib + Letrozol | Placebo + Letrozol |
Abemaciclib + NSAI | Placebo + NSAI | Abemaciclib + Fulvestrant | Placebo + Fulvestrant | |
| Menopausal status | ||||||||||
| Pre/perimenopausal | 0 | 0 | 21 | 21 | 0 | 0 | 0 | 0 | 16 | 19 |
| Postmenopausal | 100 | 100 | 79 | 79 | 100 | 100 | 100 | 100 | 83 | 81 |
| Gender | ||||||||||
| Female | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Male | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Disease-free interval | ||||||||||
| Newly metastatic | 38 | 36 | 0 | 0 | 34 | 34 | 41 | 37 | na | na |
| <12 months | 22 | 22 | 5 | 2 | 1 | 3 | na | na | ||
| >12 months | 40 | 42 | 95 | 98 | 65 | 63 | na | na | ||
| Treatment-free interval | ||||||||||
| <36 months | na | na | na | na | na | na | 28 | 40 | na | na |
| ≥36months | 63 | 50 | ||||||||
| unknown | 9 | 10 | ||||||||
| Prior neo-/adjuvant chemotherapy | 48 | 49 | 40 | 43 | 44 | 43 | 38 | 40 | 60 | 60 |
| Prior therapies for advanced BC | ||||||||||
| 1 | 0 | 0 | 38 | 40 | 0 | 0 | 0 | 0 | 38 | 38 |
| >2 (%) | 0 | 0 | 38 | 34 | 0 | 0 | 0 | 0 | 0 | 0 |
Pages 5: The text on abemaciclib in the MONARCH 1 study has been corrected to:
Abemaciclib led to an ORR of 19.7%, CBR of 42.4% and median PFS of 6.0 months. The most common AEs all grades were diarrhea (90.2%), fatigue (65.2%), nausea (64.4%), decreased appetite (45.5%), and abdominal pain (38.6%).
Page 6. The first sentence on adjuvant setting has been corrected to:
In addition to the neoadjuvant setting, two prospective randomised phase III trials evaluating the role of the three different CDK4/6 inhibitors as adjuvant therapy when added to standard ET are currently ongoing (palbociclib: PALLAS, NCT02513394; abemaciclib: MonarchE, NCT03155997).
Page 8. The first and last author’s competing interests have been updated:
MP: Honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome.
CZ: Honoraria from Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Shire.