1Department of Medicine, University of California San Francisco, San Francisco, CA, USA
2Cancer Research Institute, Seoul National University, Seoul, Korea
3Translational Medicine, Seoul National University College of Medicine, Seoul, Korea
4Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2023 by the Korean Cancer Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Author Contributions
Wrote the paper: Lee EY, Lee DW, Lee KH, Im SA.
Revision: Lee EY, Lee DW, Lee KH, Im SA.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Trial | Phase | Treatment arms | No. of patients | Menopausal status | First or second-line setting (if second-line, indications are included) | Median PFS (95% CI, mo) | Median OS (95% CI, mo) | |
---|---|---|---|---|---|---|---|---|
Trials with AIs as the backbone endocrine therapy agent | ||||||||
PALOMA-1 | II | Palbociclib+letrozole vs. letrozole | 165 | Postmenopausal | First-line | 20.2 (13.8-27.5) vs. 10.2 (5.7-12.6) | 37.5 (31.4-47.8) vs. 34.5 (27.4-42.6) | |
HR 0.488 (0.319-0.748, p=0.0004) [11] | HR 0.897 (0.623-1.294, p=0.281) [11] | |||||||
PALOMA-2 | III | Palbociclib+letrozole vs. placebo+letrozole | 666 | Postmenopausal | First-line | 24.8 (22.1-not estimable) vs. 14.5 (12.9-17.1) | 53.9 (49.8-60.8) vs. 51.2 (43.7-58.9) | |
HR 0.58 (95% CI, 0.46-9.72, p < 0.001) [12] | HR 0.956 (0.777-1.177, p=0.03378) [24] | |||||||
MONALEESA-2 | III | Ribociclib+letrozole vs. placebo+letrozole | 668 | Postmenopausal | First-line | 25.3 (23.0-30.3) vs. 16.0 (13.4-18.2) | 63.9 (52.4-71.0) vs. 51.4 (47.2-59.7) | |
HR 0.568 (0.457-0.704, p=9.63×10-8) [13,14] | HR 0.76, (0.63-0.93, p=0.008) [25] | |||||||
MONARCH-3 | III | Abemaciclib+NSAI vs. placebo+NSAI | 493 | Postmenopausal | First-line | 28.18 vs. 14.76; 95% CIs, not reported | 67.1 vs. 65.1; 95% CIs, not reported | |
HR 0.540 (0.418-0.698, p=0.000002) [17] | HR 0.754 (0.584-0.974, p=0.0301) [18] | |||||||
MONALEESA-7 | III | Ribociclib+tamoxifen or NSAI+goserelin vs. placebo+tamoxifen or NSAI+goserelin | 672 | Premenopausal | First and second-line (for patients who received up to one previous line of chemotherapy for advanced disease) | Overall: 23.8 (19.2-not reached) vs. 13.0 (11.0-16.4) | Overall: 58.7 vs. 48.0; 95% CIs, not reported | |
HR 0.55 (0.44-0.69, p < 0.0001) [22] | HR 0.76 (0.61-0.96 p=not reported) [15,16] | |||||||
Chemotherapy subgroup: 46.8% vs. 61.7% event rate; HR 0.55 (0.31-0.95) | Chemotherapy subgroup: 27.7% vs. 40.4% event rate; HR 0.67 (0.33-1.35) | |||||||
Trials with fulvestrant as the backbone endocrine therapy agent | ||||||||
PALOMA-3 | III | Palbociclib+fulvestrant vs. placebo+fulvestrant | 521 | Any | Second-line (progression during or ≤ 1 month after for endocrine therapy metastasis, progression during or ≤ 12 months after completion or discontinuation of adjuvant therapy) | 9.5 (9.2-11.0) vs. 4.6 (3.5-5.6) | 34.9 (28.8-40.0) vs. 28.0 (23.6-34.6) | |
Note: pre or perimenopausal patients received goserelin | HR 0.46 (0.36-0.59, p < 0.0001) [20,23] | HR 0.81 (0.64-1.03, p=0.09) [20,23] | ||||||
MONARCH-2 | III | Abemaciclib+fulvestrant vs. placebo+fulvestrant | 669 | Any | Second-line (progression on neoadjuvant or adjuvant endocrine therapy, ≤ 12 months after adjuvant endocrine therapy, or during endocrine therapy for advanced disease) | 16.4 vs. 9.3; 95% CIs, not reported | 46.7 vs. 37.3; 95% CIs, not reported | |
HR 0.553 (0.449-0.681, p < 0.001) [21] | HR 0.757 (0.606-0.945, p=0.01) [26] | |||||||
MONALEESA-3 | III | Ribociclib+fulvestrant vs. placebo+fulvestrant | 484 | Postmenopausal | First- and second-line (for patients who progressed after one line of endocrine therapy for advanced disease without prior (neo)adjuvant treatment for early disease) | 20.5 (18.5-23.5) vs. 12.8 (10.9-16.3) | Not reached vs. 51.8 | |
HR 0.593 (0.480-0.732, p < 0.001) [19] | HR 0.64 (0.46-0.88) [19] | |||||||
Endocrine therapy subgroup: 56% vs. 77% event rate; HR 0.565 (0.428-0.744) | Endocrine therapy subgroup: 61.6% vs. 70.3% event rate; HR 0.74 (0.56-0.98) |
CDK4/6, cyclin-dependent kinase 4/6; CI, confidence interval; HR, hazard ratio; NSAI, nonsteroidal aromatase inhibitor; OS, overall survival; PFS, progression-free survival.