Background: We investigated the efficacy and health-related quality of life (HRQoL) in patients receiving either ribociclib plus endocrine therapy (ET) or chemotherapy with/without bevacizumab as first-line treatment of metastatic hormone receptor (HR)-positive, HER2-negative breast cancer (BC). Patients and Methods: In this randomized, phase III study (RIBBIT), 38 patients diagnosed with metastatic HR-positive, HER2-negative BC with presence of visceral metastases recruited between May 2018 and December 2020 were randomly assigned in a 1:1 ratio to either arm A (ribociclib + ET) or arm B (chemotherapy with/without bevacizumab) at 12 sites in Germany. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS), patient-reported HRQoL, and frequency and type of adverse events. During study conduction, the recruitment rate was persistently and considerably lower than originally expected. Therefore, the recruitment was ended prematurely. The study was initially designed to enroll and randomize 158 patients. Results: Median [95% CI] PFS was 27.3 months [19.1 – NA, parameter not estimable] in arm A and 15.8 months [8.2 – NA] in arm B. Complete responses were achieved only in arm A (n = 2, 10.5%). The ORR [95% CI] between arm A (57.9% [33.5–79.7]) and arm B (52.6% [28.9–75.6]) was comparable. Median OS [95% CI] was not reached in arm A, while in arm B median OS was 28.4 months [25.0 – NA]. Patients in arm A reported less burden by side-effects. No new safety signals emerged. Conclusion: Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency toward a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

1.
Robert-Koch-Institut
.
Gesellschaft der epidemiologischen Krebsregister
. In:
Deutschland
EV
, editor.
Krebs in Deutschland für 2017/2018. Häufigkeiten und Trends. 13. Ausgabe
Berlin
Robert-Koch-Institut
.
2021
.
2.
395137_GI_Kisqali.pdf. [cited 2022 Sep 23]. Available from: https://www.novartis.com/de-de/sites/novartis_de/files/395137_GI_Kisqali.pdf.
3.
Slamon
DJ
,
Neven
P
,
Chia
S
,
Fasching
PA
,
De Laurentiis
M
,
Im
S-A
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
.
2018
;
36
(
24
):
2465
72
.
4.
Tripathy
D
,
Im
S-A
,
Colleoni
M
,
Franke
F
,
Bardia
A
,
Harbeck
N
et al
.
Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial
.
Lancet Oncol
.
2018
;
19
(
7
):
904
15
.
5.
Bardia
A
,
Modi
S
,
Chavez-Mac Gregor
M
,
Kittaneh
M
,
Marino
AJ
,
Matano
A
et al
.
Phase Ib/II study of LEE011, everolimus, and exemestane in postmenopausal women with ER+/HER2− metastatic breast cancer
.
J Clin Orthod
.
2014
32
15_suppl
535
–.
6.
Munster
P
,
Ismail-Khan
R
,
Garcia-Estevez
L
,
Mayer
I
,
Becerra
C
,
Hamilton
E
et al
.
Abstract P4-22-18: phase Ib safety, efficacy, and molecular analysis of ribociclib (LEE011) plus letrozole for the treatment of ER+, HER2– advanced breast cancer
.
Cancer Res
.
2017
77
4_Supplement
P4-22-18-P4-22-18
.
7.
Juric
D
,
Hamilton
E
,
Garcia Estévez
L
,
De Boer
RH
,
Mayer
I
,
Campone
M
et al
.
Abstract P5-19-24: phase Ib/II study of LEE011 and BYL719 and letrozole in ER+, HER2– breast cancer: safety, preliminary efficacy and molecular analysis
.
Cancer Res
.
2015
75
9_Supplement
P5-19-24-P5-19-24
.
8.
Tolaney
S
,
Forero-Torres
A
,
Boni
V
,
Bachelot
T
,
Lu
Y-S
,
Maur
M
et al
.
Abstract P4-22-12: ribociclib + fulvestrant in postmenopausal women with HR+, HER2– advanced breast cancer (ABC)
.
Cancer Res
.
2017
77
4_Supplement
P4-22-12-P4-22-12
.
9.
Juric
D
,
Ismail-Khan
R
,
Campone
M
,
Estevez Garcia
L
,
Becerra
C
,
Boer
R
et al
. Phase Ib study of ribociclib and alpelisib and letrozole in ER+, HER2– advanced breast cancer: safety, preliminary efficacy and molecular analysis.
2015
.
10.
Ribociclib as first-line therapy for HR-positive, advanced breast cancer
.
N Engl J Med
.
2018
;
379
(
26
):
2582
.
11.
Curigliano
G
,
Gómez Pardo
P
,
Meric-Bernstam
F
,
Conte
P
,
Lolkema
MP
,
Beck
JT
et al
.
Ribociclib plus letrozole in early breast cancer: a presurgical, window-of-opportunity study
.
Breast
.
2016
;
28
:
191
8
.
12.
Hortobagyi
GN
,
Stemmer
SM
,
Burris
HA
,
Yap
Y-S
,
Sonke
GS
,
Paluch-Shimon
S
et al
.
Ribociclib as first-line therapy for HR-positive, advanced breast cancer
.
N Engl J Med
.
2016
;
375
(
18
):
1738
48
.
13.
Hortobagyi
GN
,
Stemmer
SM
,
Burris
HA
,
Yap
Y-S
,
Sonke
GS
,
Hart
L
et al
.
Overall survival with ribociclib plus letrozole in advanced breast cancer
.
N Engl J Med
.
2022
;
386
(
10
):
942
50
.
14.
Neven
P
,
Fasching
PA
,
Chia
S
,
Jerusalem
G
,
De Laurentiis
M
,
Im
S-A
et al
.
LBA4 Updated overall survival (OS) results from the first-line (1L) population in the phase III MONALEESA-3 trial of postmenopausal patients (PTS) with HR+/HER2− advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL)
.
Ann Oncol
.
2022
33
S194
.
15.
Goetz
MP
,
Toi
M
,
Campone
M
,
Sohn
J
,
Paluch-Shimon
S
,
Huober
J
et al
.
Monarch 3: abemaciclib as initial therapy for advanced breast cancer
.
J Clin Oncol
.
2017
;
35
(
32
):
3638
46
.
16.
Cristofanilli
M
,
Rugo
HS
,
Im
S-A
,
Slamon
DJ
,
Harbeck
N
,
Bondarenko
I
et al
.
Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): updated analyses from PALOMA-3
.
J Clin Orthod
.
2021
39
15_suppl
1000
.
17.
Finn
RS
,
Martin
M
,
Rugo
HS
,
Jones
S
,
Im
S-A
,
Gelmon
K
et al
.
Palbociclib and letrozole in advanced breast cancer
.
N Engl J Med
.
2016
;
375
(
20
):
1925
36
.
18.
Neven
P
,
Rugo
HS
,
Tolaney
SM
,
Iwata
H
,
Toi
M
,
Goetz
MP
et al
.
Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial
.
Breast Cancer Res
.
2021
;
23
(
1
):
87
.
19.
Miller
K
,
Wang
M
,
Gralow
J
,
Dickler
M
,
Cobleigh
M
,
Perez
EA
et al
.
Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer
.
N Engl J Med
.
2007
;
357
(
26
):
2666
76
.
20.
Zielinski
C
,
Láng
I
,
Inbar
M
,
Kahán
Z
,
Greil
R
,
Beslija
S
et al
.
Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial
.
Lancet Oncol
.
2016
;
17
(
9
):
1230
9
.
21.
RECISTGuidelines.pdf. [cited 2022 Sep 14]. Available from: https://project.eortc.org/recist/wp-content/uploads/sites/4/2015/03/RECISTGuidelines.pdf.
22.
EORTC
EORTC QLQ-C30 Fragebogen
.
1995
. Available from: https://www.ql-recorder.com/document/promotio/diss_dh.pdf.
23.
Kaplan
EL
,
Meier
P
.
Nonparametric estimation from incomplete observations
.
J Am Stat Assoc
.
1958
;
53
(
282
):
457
81
.
24.
Intguide_21_0_english.pdf. [cited 2022 Sep 20]. Available from: https://admin.meddra.org/sites/default/files/guidance/file/intguide_21_0_english.pdf.
25.
Common Terminology Criteria for Adverse Events (CTCAE)
. Available from: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.
26.
Slamon
DJ
,
Neven
P
,
Chia
S
,
Jerusalem
G
,
De Laurentiis
M
,
Im
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
.
2021
;
32
(
8
):
1015
24
.
27.
Martin
M
,
Zielinski
C
,
Ruiz-Borrego
M
,
Carrasco
E
,
Ciruelos
E
,
Munoz
M
et al
.
GS2-07. Results from PEARL study (GEICAM/2013-02_CECOG/BC.1.3.006): a phase 3 trial of Palbociclib (PAL) in combination with endocrine therapy (ET) versus Capecitabine (CAPE) in hormonal receptor (HR)-positive/human epidermal growth factor receptor (HER) 2-negative metastatic breast cancer (MBC) patients (pts) whose disease progressed on aromatase inhibitors (AIs)
.
Cancer Res
.
2020
80
4_Supplement
GS2-07
.
28.
El Saghir
N
,
Malwinder
S
,
Azim
H
,
Eralp
Y
,
Im
S-A
,
Yap
YS
et al
.
RIbociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with HR+, HER2– inoperable locally advanced or metastatic breast cancer: RIGHT choice study
.
Ann Oncol
.
2019
30
v140
1
.
29.
Fasching
PA
,
Bardia
A
,
Nusch
A
,
Jerusalem
G
,
Chan
A
,
El Saghir
N
et al
.
276O Pooled analysis of patient (pt)-reported quality of life (QOL) in the MONALEESA (ML)-2, -3, and -7 trials of ribociclib (RIB) plus endocrine therapy (ET) to treat hormone receptor–positive, HER2-negative (HR+/HER2−) advanced breast cancer (ABC)
.
Ann Oncol
.
2020
31
S350
1
.
You do not currently have access to this content.