KR2306144825 Figure 1.

Study Design Primary endpoint

Poster 1063 INTRODUCTION METHODS • Pre- and perimenopausal
women
• PFSg
RIB (600 mg, 3 weeks on/1 Secondary endpoints
• Younger women with aggressive advanced breast cancer (ABC) usually have a worse prognosis1 • In the RIGHT Choice trial, pre- and perimenopausal women with aggressive HR+/HER2− ABC and no prior • HR+/ HER2– ABC (>10% ER+) week off) + ET • TTF
Nagi S. El Saghir − Combination chemotherapy (combo CT) is often thought to be better than single-agent CT for this patient population due to its higher efficacy and the systemic therapy for ABC were randomized 1:1 to receive either RIB with letrozole/anastrozole + goserelin • No prior systemic therapy for • 3-month TFR
[email protected] potential ability of younger patients to tolerate the toxicities associated with it2-4 or physician’s choice of combo CT (Figure 1) ABC R 1:1e • ORR
− Patients included in the trial had ABC not amenable to curative therapy for which combo CT was clinically • Measurable disease • CBR
• The phase 2 RIGHT Choice trial in pre- and perimenopausal women with hormone-receptor positive, HER2-negative (HR+/HER2−) ABC with aggressive Physician’s choice of
• Aggressive diseasea • TTR
indicated by physician’s judgment. Included patients were required to fulfill ≥1 of the following criteria:
Outcomes with first-line ribociclib + features of rapidly progressing or highly symptomatic disease, including physician-assessed visceral crisis, reported a statistically significant median
progression-free survival (mPFS) benefit of ≈1 year with ribociclib (RIB) + endocrine therapy (ET) vs combo CT (24.0 vs 12.3 months; hazard ratio [HR], ▪ Symptomatic visceral metastases
• ECOG PS ≤2b
• Total bilirubin ≤1.5 × ULNc
combo CTf
Docetaxel + capecitabine • OS
Paclitaxel + gemcitabine • Safety
endocrine therapy vs physician’s 0.54; 95% CI, 0.36-0.79; P=.0007)5
• While RIB + ET has previously demonstrated PFS and overall survival (OS) benefits over ET alone in the exploratory analysis of pre- and perimenopausal
▪ Rapid progression of disease or impending visceral compromise • N=222d Capecitabine + vinorelbine • QOL
▪ Markedly symptomatic nonvisceral disease CBR, clinical benefit rate; ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; ORR, overall response

choice combination chemotherapy by women <40 and ≥40 years of age with HR+/HER2− ABC in the MONALEESA-7 trial, the efficacy of RIB + ET vs combo CT in pre- and perimenopausal
women with aggressive ABC by age (<40 and ≥40 years) has not been directly compared6-8
• HRs for PFS and time to treatment failure (TTF) in the 2 subgroups were obtained from Cox proportional
rate; QOL, quality of life; R, randomized; RECIST, Response Evaluation Criteria in Solid Tumors; TFR, treatment failure rate; TTR, time to
response; ULN, upper limit of normal. a For which combo CT is clinically indicated by physician’s judgment; b For patients with ECOG PS 2, the
poor PS should be due to breast cancer; c In patients with liver metastases; d Patients were enrolled from Feb 2019 to Nov 2021; e Stratified by
hazards model stratified by randomization stratification factor per interactive response technology
age in pre/perimenopausal patients • Here we present subgroup analyses of key efficacy endpoints from the RIGHT Choice trial in patients <40 and ≥40 years of age • Data cutoff for this analysis was April 12, 2022
the presence or absence of liver metastases and by disease-free interval (duration from date of complete tumor resection of primary breast
cancer lesion to the date of documented disease recurrence) of <2 or ≥2 years; f If one of the combo CT drugs was stopped due to toxicity, the
patient was allowed to continue on the other, better-tolerated CT drug (monotherapy); g PFS locally assessed per RECIST 1.1.

with aggressive HR+/HER2− advanced

RESULTS
breast cancer: a subgroup analysis of Baseline Characteristics and Disease History TTF and TFR in Patients <40 Years and ≥40 Years of Age Figure 5. Time to Response by Age Subgroups
the RIGHT Choice trial • In total, 70 pre- and perimenopausal patients were <40 years old, and 152 were ≥40 years old • In patients <40 years of age, there was a 70% relative reduction in risk of treatment failure with RIB + ET vs A. Age <40 years B. Age ≥40 years
• Demographics and baseline clinical characteristics were generally well-balanced across RIB + ET and combo CT (Figure 3A) 100 100
combo CT arms in both age subgroups (Table 1) − The 3-month TFR with RIB + ET was 16.9% lower than with combo CT (RIB arm; n=3; 9.4%; 95% CI,
Nagi S. El Saghir,1
Yoon-Sim Yap,2
Yesim Eralp,3
Seock-Ah Hamdy Im,4 Julie Azim,5 Rihani,6 Table 1. Demographics and Baseline Clinical Characteristics of Patients by Age Subgroup 2.0%-25.0% vs CT arm; n=10; 26.3%; 95% CI, 13.4%-43.1%) 80 80
Nikita Volkov, Shin-Cheh Chen, Hakan Harputluoglu, Patrapim Sunpaweravong,10
7 8 9

Yuan-Ching Chang,11 Teresa Delgar Alfaro,12 Jiwen Wu,13 Huilin Hu,13 Melissa Gao,12
Age <40 years Age ≥40 years − Among patients receiving combo CT, those aged <40 years had a shorter median TTF and higher 3-month 60 60

TTR, %

TTR, %
Yen Shen Lu14
Parameter RIB + ET Combo CT RIB + ET Combo CT TFR than patients aged ≥40 years (Figure 3)
n=32 n=38 n=80 n=72
• In patients ≥40 years of age, there was a 42% relative reduction in risk of treatment failure with RIB + ET vs 40 RIB + ET Combo CT 40 RIB + ET Combo CT
Age, median, years 36.0 35.0 45.0 46.0
Race, n (%)a combo CT (Figure 3B) Events/n 21/32 22/38 Events/n 52/80 44/72
1 American University of Beirut Medical Center, Beirut, Lebanon; 2National Cancer Centre Singapore, Asian 18 (56.3) 19 (50.0) 42 (52.5) 39 (54.2) 20 20
Singapore; 3Acıbadem Research Institute of Senology, Acıbadem University, Istanbul, Turkey; 4Seoul National – The 3-month TFR with RIB + ET was 6.9% lower than with combo CT (RIB arm; n=10; 12.5%; 95% CI, TTR, median TTR, median
White 14 (43.8) 19 (50.0) 37 (46.3) 33 (45.8) 4.7 (2.8-15.9) 2.7 (1.4-4.9) 6.3 (4.4-12.9) 4.5 (2.8-8.4)
University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, (95% CI), moa (95% CI), moa
Histological grade, n (%)b 6.2%-21.8% vs CT arm; n=14; 19.4%; 95% CI, 11.1%-30.5%) 0 0
Republic of Korea; 5School of Medicine, Cairo University, Cairo, Egypt; 6Independent Patient Advocate,
Amman, Jordan; 7City Cancer Center, Saint Petersburg, Russia; 8Department of General Surgery, Chang 1 2 (6.3) 7 (18.4) 8 (10.0) 9 (12.5)
0 3 6 9 12 15 18 21 24 27 30 33 36 39 0 3 6 9 12 15 18 21 24 27 30 33 36 39
Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan 333, Taiwan; 9Inonu University, Malatya, 2 21 (65.6) 21 (55.3) 45 (56.3) 40 (55.6)
9 (28.1) 6 (15.8) 26 (32.5) 23 (31.9) Figure 3. Time to Treatment Failure by Age Subgroups Time, months Time, months
Turkey; 10Unit of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla 3 No. at risk No. at risk
University, Songkhla, Thailand; 11Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C;
12 Novartis Pharma AG, Basel, Switzerland; 13 Novartis Pharmaceuticals Corporation, East Hanover, NJ;
≥50% ER+, n (%) 26 (81.3) 32 (84.2) 69 (86.3) 63 (87.5) A. Age <40 years B. Age ≥40 years RIB + ET 32 20 13 10 9 9 7 7 7 7 6 6 6 0 RIB + ET 80 52 40 32 30 29 22 22 21 19 16 16 16 0
PR+, n (%) 28 (87.5) 36 (94.7) 71 (88.8) 66 (91.7)
14 National Taiwan University Hospital, Taipei, Taiwan. Combo CT 38 11 9 7 7 7 7 7 7 7 6 6 6 0 Combo CT 72 39 26 20 18 16 14 14 13 13 13 13 13 0
Disease status, n (%)
100 100 a TTR is defined as the time from the date of randomization to the first documented response of either CR or PR without confirmation.
De novo 17 (53.1) 28 (73.7) 54 (67.5) 45 (62.5)
Visceral metastatic sites, n (%)c
Liver 18 (56.3) 24 (63.2) 38 (47.5) 33 (45.8) 80 80 Safety in Patients <40 and ≥40 Years of Age
19 (59.4) 44 (55.0) 41 (56.9)
Lung
28 (87.5)
17 (44.7)
61 (76.3) 55 (76.4)
• No new safety signals were observed in patients in the 2 subgroups in the RIB + ET arm compared with those
Liver or lung 30 (78.9) 60 60
previously reported (Table 2)

TTF %
TTF %
Aggressive disease
https://bit.ly/ElSaghirN1063 characteristics, n (%) 40 RIB + ET Combo CT 40 • Adverse events (AEs) observed with combo CT were also consistent with the historical AE profile for combo
Rapid progression 6 (18.8) 6 (15.8) 17 (21.3) 12 (16.7) RIB + ET Combo CT
Scan to obtain: 4 (12.5) 5 (13.2) 11 (13.8) 11 (15.3) CT, with higher rates of symptomatic AEs, including nausea, vomiting, fatigue, and palmar-plantar
Copies of this poster, plain language
Symptomatic nonvisceral disease Events/n 13/32 35/38 Events/n 48/80 49/72
• Poster Symptomatic visceral metastasis 22 (68.8) 27 (71.1) 52 (65.0) 49 (68.1) 20 20 erythrodysesthesia, than with RIB + ET in both subgroups
summary, and video summary obtained Median TTF, moa NR 7.0 Median TTF, moa 18.5 11.0
• Plain language summary through Quick Response (QR) code are Visceral crisis, n (%)d 16 (50.0) 17 (44.7) 45 (56.3) 38 (52.8)
for personal use only and may not be PR, progesterone receptor. a One patient in the ≥40-years subgroup in the RIB arm was African American; b Histological grade data were missing for 4 patients in the combo CT arm in the 0 HR (95% CI) 0.30 (0.15-0.58) 0
HR (95% CI) 0.58 (0.38-0.88) Table 2. AEs ≥20% Irrespective of Causality in Either Treatment Arm in Both Age Groups
reproduced without permission of the <40-years subgroup and for 1 patient in the RIB + ET arm in the ≥40-years subgroup; c The same patient may have multiple visceral metastatic sites; d Based on physician’s judgment,
authors which followed ABC3 guidelines available at the time of study design.
Age <40 yearsa Age ≥40 yearsa
0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 6 9 12 15 18 21 24 27 30 33 36 RIB + ET Combo CT RIB + ET Combo CT
PFS in Patients <40 and ≥40 Years of Age No. at risk
Time, months
No. at risk
Time, months
AE Grouping, n (%)
n=32 n=32 n=80 n=68
All G G3/4 All G G3/4 All G G3/4 All G G3/4
• In patients <40 years of age, RIB + ET was associated with a 62% relative reduction in risk of disease RIB + ET 32 29 25 19 15 14 11 9 6 2 1 1 0 RIB + ET 80 70 63 53 48 42 34 27 18 6 1 0 0
Combo CT Hematologic AEs
progression or death vs combo CT (Figure 2A) 38 28 24 15 9 6 4 2 1 1 0 0 0 Combo CT 72 58 51 32 28 20 16 10 5 2 1 0 0
25 19 14 10 67 46 35 25
– In the combo CT arm, patients aged <40 years had a shorter mPFS than patients aged ≥40 years NR, not reached; a TTF is defined as the time from randomization to progression, death, change to other anticancer therapy, or discontinuation.
Neutropenia
KEY FINDINGS AND CONCLUSIONS (Figure 2)
(78.1)
15
(59.4)
7
(43.8)
6
(31.3)
1
(83.8)
39
(57.5)
19
(51.5)
20
(36.8)
6
• In patients ≥40 years of age, RIB + ET was associated with a 29% relative reduction in risk of disease ORR, CBR, and TTR in Patients <40 and ≥40 Years of Age Leukopenia
(46.9) (21.9) (18.8) (3.1) (48.8) (23.8) (29.4) (8.8)
10 3 10 4 28 3 30 5
progression or death vs combo CT (Figure 2B) • For both patients <40 and ≥40 years of age, the ORR and the CBR were similar between the RIB + ET and Anemia
• This exploratory age subgroup analysis of patients with aggressive Figure 2. PFS by Age Subgroups combo CT arms (Figures 4A and 4B) (31.3) (9.4) (31.3) (12.5) (35.0) (3.8) (44.1) (7.4)
Elevated aspartate 6 4 7 2 16 4 22 4
HR+/HER2− ABC from the RIGHT Choice trial showed a clinically • The median TTR was similar between the RIB + ET and combo CT arms in both age subgroups (Figures aminotransferase (18.8) (12.5) (21.9) (6.3) (20.0) (5.0) (32.4) (5.9)
A. Age <40 years B. Age ≥40 years
meaningful PFS benefit and improved secondary outcomes with 5A and 5B) Elevated alanine aminotransferase
5 2 7 2 17 4 23 4
first-line RIB + ET over combo CT for patients regardless of age RIB + ET Combo CT RIB + ET Combo CT (15.6) (6.3) (21.9) (6.3) (21.3) (5.0) (33.8) (5.9)

Events/n 40/80 33/72 Figure 4. ORR and CBR by Age Subgroups Nonhematologic AEs
− While a PFS benefit with RIB + ET over combo CT was noted in 100 Events/n 12/32 25/38 100
PFS, median, mo 21.2 16.0 3 7 11 20 1
both age subgroups, it was particularly evident in patients <40 PFS, median, mo NR 10.2 A. Age <40 years B. Age ≥40 years Nausea
(9.4)
0
(21.9)
0
(13.8)
0
(29.4) (1.5)
years of age, with a 62% relative reduction in risk of progression 80 80 HR (95% CI) 0.71 (0.44-1.15) 1 10 1 11 10
HR (95% CI) 0.38 (0.18-0.79) 100% 100% Alopecia 0 0 0
or death (3.1) (31.3) (3.1) (13.8) (14.7)
60 60
PFS, %
PFS, %

80% 80% 1 12 1 4 13 1
Fatigue 0 0
• In both age subgroups, patients receiving RIB + ET showed a 40 60% 60%
(3.1) (37.5) (3.1) (5.0) (19.1) (1.5)
40 1 7 1 2 6
similar treatment response rate and time to response as patients Peripheral neuropathy
(3.1)
0
(21.9) (3.1) (2.5)
0
(8.8)
0
40% 40% 82.5% 76.4%
receiving combo CT, matching the high tumor response rate seen 20 20 65.6%
57.9%
75.0% 65.8% 65.0% 61.1%
Vomiting
1
0
7
0
7 1 23
0
with combo CT 20% 20% (3.1) (21.9) (8.8) (1.3) (33.8)
0 0 11 1 3 21 4
Palmar-plantar erythrodysesthesia 0 0 0
• Patients aged <40 years who received combo CT had worse 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
0%
a b
0%
a b
(34.4) (3.1) (3.8) (30.9) (5.9)

efficacy outcomes than patients aged ≥40 years ORR CBR ORR CBR 5 3 21 1
Time, months Time, months Diarrhea 0 0 0 0
No. at risk No. at risk (15.6) (3.8) (30.9) (1.5)
• This analysis supports RIB + ET as a preferred treatment option in RIB + ET 32 29 29 25 21 18 15 14 12 11 9 8 6 4 2 1 1 1 0 RIB + ET 80 74 70 63 57 52 48 42 38 34 27 22 18 14 5 1 1 0 0 RIB + ET Combo CT
G, grade. a 6 patients in the <40-years subgroup and 4 in the ≥40-years subgroup randomized to the combo CT arm were not included in the safety set as they did not receive any study treatment after withdrawal of
Combo CT CR, complete response; PR, partial response. a Proportion of patients with CR or PR without image confirmation; b Proportion of patients with CR or PR without image confirmation or stable disease consent following knowledge of randomization to the CT arm (n=9) and withdrawal based on physician’s decision (n=1).
patients with aggressive HR+/HER2− ABC, including younger NR, not reached.
38 29 27 24 17 15 9 6 5 4 3 2 1 1 1 0 0 0 0 Combo CT 72 61 57 51 39 31 28 20 17 16 11 7 5 5 2 1 1 0 0
or non-CR/non–progressive disease for ≥24 weeks.

patients aged <40 years who have a worse prognosis

Acknowledgments Disclosures References
The authors thank the patients enrolled in these studies and their families as well Dr El Saghir reports personal fees from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche. Dr Yap reports person al fees and travel support from Lilly/DKSH, AstraZeneca; personal fees from Novartis, Pfizer, Eisai, MSD, Inivata, Specialised T herapeutics, Roche; grants 1. Bardia A, Hurvitz S. Clin Cancer Res. 2018;24(21):5206-5218. 2. Cardoso F, et al. Ann
as the study investigators. Medical editorial assistance was provided by from MSD; Dr Eralp reports personal fees from Novartis, Gilead, Merck Sharp & Dohme, Glaxo Smith Kline, Roche; grants from Ro che; nonfinancial support from Roche, Novartis, Boston Scientific; Dr Im reports personal fees from AstraZeneca, Novartis, Hanmi , Pfizer, Eisai, Roche, Oncol. 2020;31(12):1623-1649. 3. O'Shaughnessy J. Oncologist. 2005;10 (suppl 3):20-29.
This study is sponsored by Novartis Pharma AG.
MediTech Media, Ltd, and was funded by Novartis Pharmaceuticals Corporation. Lilly, GSK, MSD, Daiichi Sankyo, Idience, Bertis; research grants from AstraZeneca, Pfizer, Eisai, Roche, Daewoong Pharm, Bor yung Pharm, Daiichi Sankyo. Dr Azim reports personal fees and nonfinancial support from Novartis, Roche, Pfizer, MSD, ASZ; perso nal fees from BMS, 4. Gennari A, et al. Ann Oncol. 2021;32(12):1475-1495. 5. Lu Y-S, et al. SABCS 2022. Oral
Poster presented at the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL, and virtual. The authors had final responsibility for the poster. Lilly; grants from Pfizer. Julie Rihani, Dr Volkov, Dr Chen, Dr Harputluoglu, Dr Sunpaweravong, and Dr Chang have nothing to disclose. Teresa Delgar Alfaro, Jiwen Wu, Huilin Hu, and Melissa Gao report employment and stock ownership from Novartis. Dr Lu reports grants and GS1-10. 6. Tripathy D, et al. Lancet Oncol. 2018;19(7):904-915. 7. Im S-A, et al. N Engl J
6/23 286802 personal fees from Novartis, Roche, Merck Sharp & Dohme, Pfizer, AstraZeneca; personal fees from Pfizer, Eisai, Eli Lilly, Da iichi Sankyo. Med. 2019;381(4):307-316. 8. Tripathy D, et al. SABCS 2020. Poster PD2-04.