402P - First-line ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in aggressive HR+/HER2− advanced breast cancer (ABC): A subgroup analysis of patients (pts) with or without visceral crisis from the phase II RIGHT choice study

Background

RIGHT Choice showed a statistically significant median progression-free survival (mPFS) benefit of ≈1 yr with first-line RIB + ET vs combo CT (HR, 0.54; P=.0007) in pts with aggressive HR+/HER2− ABC. As visceral crisis indicates need for a more rapidly efficacious treatment (tx), a subgroup analysis by visceral crisis status was performed.

Methods

Pre/perimenopausal pts (N=222) with no prior systemic therapy for aggressive HR+/HER2− ABC were randomized 1:1 to RIB + letrozole/anastrozole + goserelin or physician's choice of combo CT. Visceral crisis assessment was based on physician’s judgment, following ABC 3 guidelines available at the time.

Results

Overall, 116 (RIB + ET, n=61; CT, n=55) and 106 (RIB + ET, n=51; CT, n=55) pts presented with or without visceral crisis, respectively. In pts with visceral crisis, a mPFS of 12.9 mo was seen with RIB + ET vs 11.2 mo with combo CT (HR, 0.87). While in these pts the overall response rate (ORR) numerically favored RIB + ET, the time to treatment failure (TTF) and clinical benefit rate (CBR) were similar in both tx arms (Table). In pts with no visceral crisis, a mPFS benefit was seen with RIB + ET vs combo CT (24.0 vs 12.7 mo; HR, 0.34); also, TTF and CBR favored RIB + ET over combo CT. RIB + ET was associated with lower rates of symptomatic adverse events than combo CT in both groups. These interim results are based on the 12 Apr 2022 data cutoff; final results will be shown at ESMO 2023.

Conclusions

This analysis shows similar PFS and TTF outcomes but greater ORR with RIB + ET vs combo CT in pts with physician-assessed visceral crisis. Clinically meaningful tx benefit with RIB + ET over combo CT was seen in pts with aggressive disease not classified as visceral crisis. These findings support RIB + ET over combo CT in pts with aggressive ABC even in the presence of visceral crisis. Table: 402P

*Without image confirmation; †Docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine; ‡Not reached.

Clinical trial identification

NCT03839823.

Editorial acknowledgement

Editorial assistance in the writing of the abstract was provided by Shashank Tandon of MediTechMedia.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

H.A. Azim: Non-Financial Interests, Personal and Institutional, Other, Supporting educational activities for my academic institution: Novartis, Roche, Pfizer, MSD; Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer, MSD, BMS, ASZ, Lilly; Financial Interests, Personal, Invited Speaker: Novartis, Roche, Pfizer, MSD, BMS, ASZ, Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Other, Supporting educational activities for my academic institution: BMS, ASZ, Lilly. N.S. El Saghir: Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria for lectures and ad boards: AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche; Financial Interests, Personal, Advisory Board, Honoraria for lectures and ad boards: AstraZeneca, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche. Y.S. Yap: Financial Interests, Personal, Other, Honoraria: Pfizer, Lilly/DKSH, Eisai, AstraZeneca, MSD, Inivata, Specialized Therapeutics, Novartis, Roche; Financial Interests, Personal and Institutional, Research Grant: MSD; Non-Financial Interests, Personal, Other, Travel Support: AstraZeneca, Lilly/DKSH. Y. Eralp: Financial Interests, Personal, Advisory Board: Novartis, Merck, Sharp and Dohme, AstraZeneca; Financial Interests, Personal, Other, Educational Fee: Gilead; Financial Interests, Personal, Other, Educational Fees: Glaxo Smith Kline; Financial Interests, Personal and Institutional, Research Grant, Research Support: Roche; Non-Financial Interests, Personal, Non remunerated activity, Non-compensated educational program: Roche, Novartis; Non-Financial Interests, Personal, Non remunerated activity, Non-compensated mentorship program: Boston Scientific; Financial Interests, Personal, Other, Satellite meeting fee: Roche. S. Im: Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Eisai, Roche , Daewoong Pharm, Boryung Pharm, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Novartis, Hanmi, Pfizer, AstraZeneca, Eisai, Roche , Lilly, GSK, MSD , Daiichi Sankyo, Idience, Bertis. S. Gupta: Financial Interests, Personal, Other, Member of various committees related to guidelines, drug pricing, others: Indian Council of Medical Research, Government of India; Financial Interests, Personal, Other, Member of Scientific Committee on nano-biosensors for healthcare applications.: Council of Scientific and Industrial Research, Government of India; Financial Interests, Personal, Other, Scientific committee member for appraisal of scientific projects submitted to DBT for funding.: Department of Biotechnology, Government of India; Financial Interests, Personal, Other, Scientific committee member for appraisal of scientific projects submitted to India Alliance for funding. India Alliance is a partnership between Wellcome Trust and Department of Biotechnology (Government of India) to fund healthcare related research in India.: India Alliance; Financial Interests, Institutional, Other, Steering Committee member for a global clinical trial (CLEE011A2207). Honorarium to institution.: Novartis; Financial Interests, Institutional, Other, Steering Committee member for a global clinical trial. Honorarium to institution.: AstraZeneca; Financial Interests, Institutional, Advisory Board, Advisory Board member on ovarian cancer. Honorarium to institution.: AstraZeneca UK Limited; Financial Interests, Institutional, Advisory Board, Advisory Board member on metastatic breast cancer. Honorarium to institution: Eli Lilly & Company (India) Limited; Financial Interests, Institutional, Invited Speaker, Invited speaker on cervical cancer at an academic conference. Honorarium to institution: Seoul National University Hospital; Financial Interests, Institutional, Invited Speaker, Chairperson at a conference. Honorarium to institution.: Lupin Limited; Financial Interests, Institutional, Invited Speaker, Chairperson, speaker, or panelist at 5 conferences/meetings. Honoraria to institution.: Roche Products (India) Private Limited; Financial Interests, Institutional, Invited Speaker, Chairperson, panelist, or speaker at a 3 meetings/roundtable. Honoraria to institution: Novartis Healthcare Pvt. Ltd.; Financial Interests, Institutional, Invited Speaker, Chairperson at 2 conferences/meetings. Honoraria to institution.: Eli Lilly & Company (India) Limited; Financial Interests, Institutional, Invited Speaker, Invited speaker in a conference. Nag Foundation is a not-for-profit registered society working in the field of cancer.: Nag Foundation; Financial Interests, Institutional, Invited Speaker, Invited panelist in a meeting. 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Hoffmann-La Roche Ltd; Financial Interests, Institutional, Coordinating PI, National coordinating PI of a multi-omics study in ER positive breast cancer: Department of Biotechnology, Government of India; Financial Interests, Institutional, Local PI, EGC002: Phase III, Randomized, Multicenter, Double-blind Study to Compare Efficacy and Safety of EG12014 (EirGenix Trastuzumab) with Herceptin® as Neoadjuvant Treatment in Combination with Anthracycline/Paclitaxel-based Systemic Therapy in Patients with HER2-positive Early Breast Cancer: EirGenix Inc.; Financial Interests, Institutional, Local PI, Protocol No. - CLEE011A3201C : A phase II randomized study of the combination of Ribociclib plus goserelin acetate with Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal patients with hormone receptor-positive/HER2-negative inoperable locally advanced or metastatic breast cancer - RIGHT Choice Study: Novartis Healthcare Pvt. Ltd.; Financial Interests, Institutional, Local PI, Protocol No. - D9100C00001 : A Phase III, Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With and following Chemoradiotherapy Compared to Chemoradiotherapy Alone for Treatment in Women With Locally Advanced Cervical Cancer (CALLA): AstraZeneca Pharma India limited.; Financial Interests, Institutional, Local PI, Protocol No. - CLEE011A2207 : A phase II, multicenter, randomized, open-label study to evaluate the safety and efficacy of 400 mg of ribociclib in combination with non-steroidal aromatase inhibitors for the treatment of pre- and postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received no prior therapy for advanced disease: Novartis Healthcare Pvt. 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Ltd.; Financial Interests, Institutional, Local PI, MO42921 A multi-country observational retrospective study to evaluate the prevalence of pd-l1 and its role in patients with tnbc treated with systemic therapy (VANESSA): Roche Products India Pvt Ltd.; Financial Interests, Institutional, Local PI, Cost-effectiveness Analysis & Value-Based Pricing for Anti-Cancer Drugs: Implications for Patients, Industry, Insurer and Regulator: Department of Health Research, Ministry of Health and Family Welfare, New Delhi; Financial Interests, Institutional, Coordinating PI, Coordinating PI for Multi-Omics Analysis to Decipher Mechanisms of Hormone Resistance in Breast Cancer: Department of Biotechnology, Government of India; Financial Interests, Institutional, Coordinating PI, Mapping of Breast Cancer: Department of Science and Technology, Government of India; Financial Interests, Institutional, Local PI, Protocol No. - ECTS/16/002 : A multicentric open label phase II safety and efficacy study of ormeloxifene in tamoxifen resistant metastatic/recurrent breast cancer patients.: HLL Lifecare Limited (A Government of India Enterprises); Financial Interests, Institutional, Coordinating PI, Protocol No. - D0818R0000 : Protocol no. D0818R00001- A Non-interventional, multicentre study to assess prevalence of BRCA1 and BRCA2 mutation among ovarian, primary peritoneal and fallopian tube cancer patients in India (BRCA study): AstraZeneca Pharma India Ltd.; Financial Interests, Institutional, Local PI, Protocol No. - 1000-16 : An Open Label, Single Arm, Multicentric, Phase IV study to evaluate the safety and efficacy of Bevacizumab of Intas Pharmaceuticals Limited in approved indications: Intas Pharmaceuticals Ltd; Financial Interests, Institutional, Local PI, Protocol No. - Protocol no: 471-13 : “A Prospective, Adaptive, Randomized, Open-Label, Multicenter Clinical Trial to assess the Efficacy and Safety of Fixed Dose Combination of Capecitabine & Cyclophosphamide in Patients of Metastatic Breast Cancer with failure of Anthracycline and/or Taxane Chemotherapy: Intas Pharmaceuticals Ltd; Financial Interests, Institutional, Local PI, Protocol No. - MO39196 : A Phase III, Multicentre, randomised, double-blind, placebo controlled study of Atezolizumab (anti-PD-L1 antibody) in combination with paclitaxel compared with placebo in combination with paclitaxel for patients with previously untreated, inoperable locally advanced or metastatic Triple Negative Breast Cancer.: Roche Products (India) Pvt. Ltd; Financial Interests, Institutional, Local PI, Protocol No. - CBYL719C2301 : A phase III randomized double-blind, placebo controlled study of alpelisib (BYL719) in combination with fulvestrant for men and postmenopausal women with hormone receptor positive, HER2-negative advanced breast cancer which progressed on or after aromatase inhibitor treatment: Novartis Healthcare Pvt. Ltd.; Non-Financial Interests, Member of Board of Directors, This is a not-for-profit registered organization which aims to create large databases of genomic and other 'omic' data in breast and other cancers.: Indian Cancer Genome Atlas; Non-Financial Interests, Leadership Role, General Secretary of this non-governmental organization (It is a not-for-profit) which aims to help underprivileged patients with breast and gynecological cancers and promotes research and educational activities in these themes.: Women's Cancer Initiative - Tata Memorial Hospital; Non-Financial Interests, Leadership Role, President-Elect of ISMPO which is the largest professional organization of medical oncologists in India. It is a not-for-profit registered society.: Indian Society of Medical and Paediatric Oncology (ISMPO). T. Delgar Alfaro: Financial Interests, Personal, Stocks or ownership: Novartis; Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis. J. Wu: Financial Interests, Personal, Stocks or ownership: Novartis; Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis. H. Hu: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks or ownership: Novartis. M. Gao: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks or ownership: Novartis. Y. Lu: Financial Interests, Personal and Institutional, Other, Clinical Trial Study Fee: Novartis ; Financial Interests, Institutional, Research Grant, Grant for clinical study for ESR1 mutation detected by cell free DNA: Novartis; Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker Fee: Novatis; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultation Fee: Pfizer; Financial Interests, Institutional, Research Grant, Contracted research: Roche, Merck Sharp & Dohme, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker: Roche, Merck Sharp & Dohme, Pfizer, Eisai, AstraZeneca, Eli Lilly, Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Clinical Trial: AstraZeneca. All other authors have declared no conflicts of interest.