Righ Choise Trial

San Antonio Breast Cancer Symposium®, December 6-10, 2022
Primary Results From the Randomized Phase II

RIGHT Choice Trial of Premenopausal Patients With
Aggressive HR+/HER2− Advanced Breast Cancer
Treated With Ribociclib + Endocrine Therapy vs
Physician’s Choice Combination Chemotherapy
Yen-Shen Lu,1 Eznal Izwadi Bin Mohd Mahidin,2 Hamdy Azim,3 Yesim Eralp,4 Yoon-Sim Yap,5 Seock-Ah Im,6 Julie Rihani,7
James Bowles,8 Teresa Delgar Alfaro,8 Jiwen Wu,9 Melissa Gao,8 Khemaies Slimane,8 Nagi El Saghir10
1National Taiwan University Hospital, Taipei, Taiwan; 2Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; 3School of Medicine, Cairo
University, Cairo, Egypt; 4Acibadem Research Institute of Senology, Acibadem University, Istanbul, Turkey; 5National Cancer
Centre Singapore, Singapore; 6Seoul National University Hospital, Cancer Research Institute, Seoul National University College
of Medicine, Seoul, Republic of Korea; 7King Hussein Cancer Center, Amman, Jordan; 8Novartis Pharma AG, Basel, Switzerland;
9Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 10American University of Beirut Medical Center, Beirut, Lebanon.
This presentation is the intellectual property of the author/presenter. Contact them at yslu@ntu.edu.tw for permission to reprint and/or distribute.
Disclosure Information
Dr. Lu reports:
Grant support/research collaborations: Novartis, Pfizer, MSD, Roche, AstraZeneca,

and ACT Genomics
Advisory board/speaker invitations: Novartis, Pfizer, MSD, Roche, AstraZeneca,

Eisai, Eli Lily, Daiichi Sankyo, and EuroPharma
Background
• Chemotherapy (CT) is the standard of care in ABC with clinically aggressive disease features that
include rapidly progressing or highly symptomatic disease and life-threatening visceral crisis, which
requires rapid disease control1
• Combination CT is associated with a higher ORR and longer PFS than single-agent CT and may be
preferred for those who have a critical disease condition and may tolerate potentially toxic treatment2
• Ribociclib (RIB) + endocrine therapy (ET) demonstrated statistically significant PFS and OS benefits
over ET alone in 3 Phase III clinical trials (MONALEESA-2, -3, and -7) in patients with HR+/HER2−
ABC, including patients with visceral metastases and a high tumor burden3-11
• No data on a head-to-head comparison of CDK4/6 inhibitor + ET vs combination CT in the patient
population with aggressive HR+/HER2− disease have been published
• Here we report the prespecified primary analysis of PFS and key secondary endpoints from the
randomized, open-label, multinational, Phase II RIGHT Choice trial
ABC, advanced breast cancer; CDK4/6, cyclin-dependent kinases 4 and 6; HER2–, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; ORR, overall response rate; OS, overall
survival; PFS, progression-free survival.
1. Cardoso F, et al. Ann Oncol. 2020;31:1623-1649. 2. O'Shaughnessy J. Oncologist. 2005;10 Suppl 3:20-9. 3. Tripathy D, et al. Lancet Oncol. 2018;19:904-915. 4. Slamon DJ, et al. J Clin Oncol. 2018;36:2465-
2472. 5. Hortobagyi GN, et al. N Engl J Med. 2016;375:1738-1748. 6. Im SA, et al. N Engl J Med. 2019;381:307-316. 7. Slamon DJ, et al. N Engl J Med. 2020;382:514-524. 8. Hortobagyi GN, et al. N Engl J
Med. 2022;386:942-950. 9. Hortobagyi GN, et al. ESMO 2021. Oral LBA17_PR. 10. Tripathy D, et al. SABCS 2020. Poster PD2-04. 11. Slamon DJ, et al. ASCO 2021. Oral 1001.
RIGHT Choice study design

Primary endpoint
Ribociclib • PFS (locally assessed per
• Pre-/perimenopausal women
(600 mg, 3 weeks on/1 week off) RECIST 1.1)
• HR+/ HER2– ABC (>10% ER+)
+ Secondary endpoints
• No prior systemic therapy for ABC
Letrozole or anastrozole + • TTF
• Measurable disease per RECIST 1.1
goserelin • 3-month TFR
• Aggressive diseasea
• Symptomatic visceral metastases • ORR
R 1:1
• Rapid disease progression or • CBR
impending visceral compromise Investigators’ choice of • TTR
• Markedly symptomatic non- combination CTe • OS
visceral disease • Safety
Docetaxel + capecitabine • QOL
• ECOG PS ≤ 2b Paclitaxel + gemcitabine
• Total bilirubin ≤ 1.5 ULN Exploratory endpoints
Capecitabine + vinorelbine
• N = 222c • Biomarker analyses
• Healthcare resource utilization
Stratified by (1) the presence or absence of Tumor imaging evaluation
liver metastases and by (2) DFId < or ≥2 years Q6W for 1st 12 weeks, Q8W for
next 32 weeks, then Q12Wf
ABC, advanced breast cancer; CBR, clinical benefit rate; CT, chemotherapy; DFI, disease-free interval; ECOG PS, Eastern Cooperative Oncology Group performance status; ER+, estrogen receptor positive;
HER2–, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; Q6W, every 6 weeks; Q8W, every 8 weeks;
Q12W, every 12 weeks; QOL, quality of life; RECIST, Response Evaluation Criteria In Solid Tumors; TFR, treatment failure rate; TTF, time to treatment failure; TTR, time to response; ULN, upper limit of normal.
a Where combination CT is clinically indicated by physician’s judgment; b For patients with ECOG 2, the poor performance status should be due to breast cancer; c Patients were enrolled from Feb 2019 to Nov 2021; d
Disease-free interval is defined as the duration from date of complete tumor resection for primary breast cancer lesion to the date of documented disease recurrence; e If one of the combination CT drugs had to be
stopped because of toxicity, the patient was allowed to continue on the other, better-tolerated CT drug (monotherapy); f Until disease progression, death, withdrawal of consent, loss to follow-up, or patient/guardian
decision, and at end of treatment.
Statistical methods
• The prespecified PFS analysis was planned after disease progression or death in
approximately 110 patients
• The study had a power of 80% to detect a HR of 0.67 at a one-sided α level of 10%
• Stratified Cox regression was used to estimate the HR for PFS, TTF, and TTR
• The efficacy analyses were performed on all randomized patients, while the safety
analysis was performed on all patients who received at least one treatment dose
• Ten patients randomized to the combination CT arm were not included in the safety set
as they did not receive any study treatment after 9 of these patients withdrew consent
following knowledge of randomization to the CT arm, and 1 was withdrawn based on
physician’s decision
• OS data were immature at data cutoff (12 April 2022)
CT, chemotherapy; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; TTF, time to treatment failure; TTR, time to response.
Baseline characteristics were well balanced

RIB + ET Combo CT RIB + ET Combo CT
Parameter, n (%) Parameter, n (%)
n = 112 n = 110 n = 112 n = 110
Median age, years 44.0 43.0 Disease status
≥40 years 80 (71.4) 72 (65.5) De novo 71 (63.4) 73 (66.4)
Visceral metastatic sitesb
Racea
Liver 56 (50.0) 57 (51.8)
Asian 60 (53.6) 58 (52.7)
Lung 63 (56.3) 58 (52.7)
White 51 (45.5) 52 (47.3)
Liver or lung 89 (79.5) 85 (77.3)
Histological grade Aggressive disease characteristic
Grade 1 10 (8.9) 16 (14.5) Rapid progression 23 (20.5) 18 (16.4)
Grade 2 66 (58.9) 61 (55.5) Symptomatic non-
15 (13.4) 16 (14.5)
visceral disease
Grade 3 35 (31.3) 29 (26.4)
Symptomatic
≥50% ER+ 95 (84.8) 95 (86.4) 74 (66.1) 76 (69.1)
visceral metastases
PR+ 99 (88.4) 102 (92.7) Visceral crisisc 61 (54.5) 55 (50.0)
Combo CT, combination chemotherapy; ER+, estrogen receptor positive; ET, endocrine therapy; RIB, ribociclib.
a One patient (0.9%) in the RIB arm was African American; b The same patient may have multiple visceral metastatic sites. c Based on PI’s judgment, which followed ABC3 and NCCN guidelines, which were available at the time
of study design.
Treatment ongoing in 46% of patients in the

RIB + ET arm
RIB + ET Combination CT All Patients
n = 112 n = 110a N = 222
Patients treated
Treatment ongoingb 51 (45.5) 26 (23.6) 77 (34.7)
Reason for end of treatmentc
Progressive disease 50 (44.6) 58 (52.7) 108 (48.6)
Adverse event 8 (7.1) 3 (2.7) 11 (5.0)
Death 1 (0.9) 0 1 (0.5)
Physician decision 1 (0.9) 5 (4.5) 6 (2.7)
Subject decision 1 (0.9) 8 (7.3) 9 (4.1)
• Median duration of follow-up was 24.1 monthsd (data cutoff: 12 April 2022)
CT, chemotherapy; ET, endocrine therapy; RIB, ribociclib.
a Ten patients in CT arm did not receive any treatment; b Patients continued study treatment at the time of the cutoff (12 April 2022); c In patients who received study treatment (RIB + ET, n = 112;
combination CT, n = 100); d Time from randomization to data cutoff date.

First-line RIB + ET achieved a statistically significant

PFS benefit of ≈ 1 year over combination CT in
aggressive HR+/HER2− ABC
RIB + ET Combo CT
Events/n 52/112 58/110a
Median PFS, mo 24.0 12.3
HR (95% CI)b 0.54 (0.36-0.79)
P value .0007
ABC, advanced breast cancer; Combo CT, combination chemotherapy; ET, endocrine therapy; HER2–, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; HR, hazard ratio;
IRT, interactive response technology; PFS, progression-free survival; RIB, ribociclib.
a Ten patients in CT arm did not receive any treatment; b HR is obtained from Cox Proportional-Hazards model stratified by liver metastasis and disease-free interval per IRT.
PFS benefit with RIB + ET over combination CT was

consistent across most subgroups of patients with
aggressive HR+/HER2− ABC
ABC, advanced breast cancer; Combo CT, combination chemotherapy; ET, endocrine therapy; HER2–, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; PFS, progression-free
survival; RIB, ribociclib.
Median time to treatment failure (TTF) was longer

with RIB + ET vs combination CT
RIB + ET Combo CT
Events/n 61/112 84/110a
Median TTF, mob 18.6 8.5
HR (95% CI)c 0.45 (0.32-0.63)
• A sensitivity analysisd confirmed the TTF findings in the safety set

• The 3-month treatment failure ratee in the RIB arm was approximately half (n = 13; 11.6%; 95% CI,
6.3%-19.0%) that in the combination CT arm (n = 24; 21.8%; 95% CI, 14.5%-30.7%)
Combo CT, combination chemotherapy; ET, endocrine therapy; HR, hazard ratio; IRT, interactive response technology; RIB, ribociclib.
a Ten patients in CT arm did not receive any treatment; b Defined as the time from randomization to progression, death, change to other anticancer therapy, or discontinuation; c HR is obtained from Cox
Proportional-Hazards model stratified by liver metastasis and disease-free interval per IRT; d The sensitivity analysis excluded the 10 patients in the CT arm who did not receive any treatment; e The proportion of
patients who discontinued study treatment due to progressive disease, death, change to other anticancer therapy, or discontinuation due to reasons other than protocol violation.
ORR and CBR were similar between RIB + ET and

combination CT
RIB + ET (n = 112)
100% Combo CT (n = 110)
80%
60%
40% 80.4% 72.7%

65.2% 60.0%
20%
0%
a b
ORR CBR
• A sensitivity analysisc confirmed the ORR and CBR findings in the safety set
CBR, clinical benefit rate; Combo CT, combination chemotherapy; CR, complete response; ET, endocrine therapy; ORR, overall response rate; PD, progressive disease; PR, partial response, RIB, ribociclib;
SD, stable disease.
a Proportion of patients with CR or PR without confirmation (confirmation imaging was not mandatory according to study protocol); b Proportion of patients with CR or PR without confirmation or SD or non-
CR/non-PD ≥24 weeks; c This analysis included all patients who received ≥1 dose of any component of the study treatment (safety set).
Time to onset of response (TTR) for RIB + ET was

similar to combination CT
RIB + ET Combo CT
Events/n 73/112 66/110a
Median TTR, mob 4.9 3.2
HR (95% CI)c 0.78 (0.56-1.09)
• A sensitivity analysisd confirmed the TTR findings in the safety set
Combo CT, combination chemotherapy; CR, complete response, ET, endocrine therapy; HR, hazard ratio; IRT, interactive response technology; PR, partial response; RIB, ribociclib.
a Ten patients in CT arm did not receive any treatment; b TTR is defined as the time from the date of randomization to the first documented response of either CR or PR without confirmation (confirmation imaging was
not required according to study protocol); c HR is obtained from Cox Proportional-Hazards model stratified by liver metastasis and disease-free interval per IRT; d The sensitivity analysis excluded the 10 patients in
the CT arm who did not receive any treatment and were removed from the denominator for the CT arm.
Fewer dose reductions were observed with RIB + ET

vs combination CT
RIB + ET Combo CT
Parameter, n (%)
n = 112 n = 100a
Number of dose reductions
0 81 (72.3) 54 (54.0)
1 27 (24.1) 12 (12.0)
2 4 (3.6) 14 (14.0)
≥3 0 20 (20.0)
• The median duration of exposure to study treatment was 15.0 months (Q1-Q3,
7.4-24.5 months) in the RIB arm and 8.6 months (Q1-Q3, 6.1-15.0 months) in the
combination CT armb
Combo CT, combination chemotherapy; ET, endocrine therapy; RIB, ribociclib; Q1, quartile 1; Q3, quartile 3.
a Ten patients in CT arm that did not receive any treatment were not included in the safety set; b Duration from start of treatment to last treatment as per data cutoff date.
Fewer TRAEs with RIB + ET vs combination CT

n (%) RIB + ET; n = 112 Combination CT; n = 100a
All Grade Grade 3/4 All Grade Grade 3/4
Total AEs 112 (100.0) 84 (75.0) 100 (100.0) 71 (71.0)
Treatment-related serious AEs 2 (1.8) 1 (0.9) 8 (8.0) 7 (7.0)
Treatment-related AEs leading to discontinuationb 8 (7.1) 7 (6.3) 23 (23.0) 7 (7.0)
• Two patients (1.8%) in RIB armc and none in CT arm showed grade ≥3 QT prolongation
AE, adverse event; CT, chemotherapy; ET, endocrine therapy; RIB; ribociclib; TRAE, treatment-related adverse event. a Ten patients in CT arm that did not receive any treatment were not included in the safety set;
b AEs leading to discontinuation of any component of the study treatment are included. c Without evidence of arrythmia.
Conclusions
• RIGHT Choice is the first prospective study comparing a CDK4/6 inhibitor + ET with combination
CT and demonstrating the PFS superiority of RIB + ET over combination CT in patients with
HR+/HER2− ABC with aggressive clinical features of rapidly progressing or highly symptomatic
disease, including visceral crisis
• First-line RIB + ET demonstrated a statistically significant PFS benefit (≈1 year longer) vs combination CT
(24.0 vs 12.3 months; HR, 0.54) in pre/perimenopausal patients with aggressive HR+/HER2− ABC
• RIB + ET also showed longer TTF than combination CT with similar TTR and ORR between the
two treatment groups, matching the high tumor response rate seen with combination CT
• No new safety signals were observed with RIB + ET
• Compared with RIB +ET, combination CT was associated with higher rates of treatment-related AEs,
many that impact QOL
• First-line RIB + ET offers an efficacious, clinically meaningful treatment option for patients with
aggressive HR+/HER2− ABC, obviating the need for combination CT and related toxicities
ABC, advanced breast cancer; AE, adverse event; CDK4/6, cyclin-dependent kinases 4 and 6; CT, chemotherapy; ET, endocrine therapy; HER2–, human epidermal growth factor receptor 2 negative; HR+,
hormone receptor positive; HR, hazard ratio; ORR, overall response rate; PFS, progression-free survival; QOL, quality of life; RIB, ribociclib; TFR, treatment failure rate; TTF, time to treatment failure; TTR, time
to response.
Acknowledgments
• This trial was funded by Novartis Pharma AG

• We thank the patients enrolled in the study and their families
• We also thank Dr. Malwinder Singh Sandhu, the study investigators, and the team
that supported this trial
• Medical editorial assistance was provided by MediTech Media, Ltd, and was funded by
Novartis Pharma AG. The authors had final responsibility for the presentation
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San Antonio Breast Cancer Symposium®, December 6-10, 2022

Primary Results From the Randomized Phase II

Grant support/research collaborations: Novartis, Pfizer, MSD, Roche, AstraZeneca,

Advisory board/speaker invitations: Novartis, Pfizer, MSD, Roche, AstraZeneca,

RIGHT Choice study design

Baseline characteristics were well balanced

Treatment ongoing in 46% of patients in the

combination CT, n = 100); d Time from randomization to data cutoff date.

First-line RIB + ET achieved a statistically significant

PFS benefit with RIB + ET over combination CT was

Median time to treatment failure (TTF) was longer

• A sensitivity analysisd confirmed the TTF findings in the safety set

ORR and CBR were similar between RIB + ET and

40% 80.4% 72.7%

Time to onset of response (TTR) for RIB + ET was

• A sensitivity analysisd confirmed the TTR findings in the safety set

Fewer dose reductions were observed with RIB + ET

Fewer TRAEs with RIB + ET vs combination CT

• This trial was funded by Novartis Pharma AG

Egypt Saudi Arabia

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