Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR <sup>+</sup>/HER2 <sup>−</sup> Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial

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Abstract

Purpose:

Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR ⁺), HER2-negative (HER2 ⁻) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months).

Patients and Methods:

Patients were randomized to receive ET [goserelin plus nonsteroidal aromatase inhibitor (NSAI) or tamoxifen] with ribociclib or placebo. OS was evaluated with a stratified Cox proportional hazard model and summarized with Kaplan–Meier methods.

Results:

The intent-to-treat population included 672 patients. Median OS was 58.7 months with ribociclib versus 48.0 months with placebo [hazard ratio = 0.76; 95% confidence interval (CI), 0.61–0.96]. Kaplan–Meier estimated OS at 48 months was 60% and 50% with ribociclib and placebo, respectively. Subgroup analyses were generally consistent with the OS benefit, including patients who received NSAI and patients aged less than 40 years. Subsequent antineoplastic therapies following discontinuation were balanced between the ribociclib (77%) and placebo (78%) groups. Use of cyclin-dependent kinase 4/6 inhibitors after discontinuation was higher with placebo (26%) versus ribociclib (13%). Time to first chemotherapy was significantly delayed with ribociclib versus placebo. No drug–drug interactions were observed between ribociclib and either NSAI.

Conclusions:

Ribociclib plus ET continued to show significantly longer OS than ET alone in pre-/perimenopausal patients, including patients aged less than 40 years, with HR ⁺/HER2 ⁻ ABC with 53.5 months of median follow-up (ClinicalTrials.gov, NCT02278120).

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Most cited references 19

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Article: not found

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

E A Eisenhauer, P Therasse, J. Bogaerts … (2009)

Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

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Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer

Gabriel N Hortobagyi, Salomon Stemmer, Howard Burris … (2016)

Background The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). Methods In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10(-5). Results The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10(-6) for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. Conclusions Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).

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Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: MONALEESA-3

Dennis J Slamon, Patrick Neven, Stephen Chia … (2018)

Journal of Clinical Oncology, 36(24), 2465-2472

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Author and article information

Journal

Journal ID (nlm-ta): Clin Cancer Res

Journal ID (iso-abbrev): Clin Cancer Res

Title: Clinical Cancer Research

Publisher: American Association for Cancer Research

ISSN (Print): 1078-0432

ISSN (Electronic): 1557-3265

Publication date (Print): 01 March 2022

Publication date (Electronic): 27 December 2021

Volume: 28

Issue: 5

Pages: 851-859

Affiliations

[1 ]Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

[2 ]Seoul National University Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

[3 ]Division of Medical Senology, European Institute of Oncology (IEO), IRCCS, Milan, Italy.

[4 ]Hospital de Caridade de Ijuí, CACON, Ijuí, Brazil.

[5 ]Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.

[6 ]Breast Unit, Champalimaud Foundation/Clinical Center, Lisbon, Portugal.

[7 ]Breast Center, Department of Obstetrics and Gynecology, Ludwig-Maximilians-University Munich, Munich, Germany.

[8 ]UCLA Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.

[9 ]Organisation for Oncology and Translational Research, Hong Kong.

[10 ]Severance Hospital of Yonsei University Health System, Seoul, Republic of Korea.

[11 ]Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.

[12 ]Centro Oncológico Estatal, Instituto de Seguridad Social del Estado de México y Municipios, Toluca, Mexico.

[13 ]Institut Català d'Oncologia, Hospital Moisès Broggi, Barcelona, Spain.

[14 ]Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

[15 ]HCG Curie Centre of Oncology and Kidwai Memorial Institute of Oncology, Bangalore, India.

[16 ]University of Ottawa, Ottawa, Ontario, Canada.

[17 ]Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.

[18 ]Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

[19 ]Breast Unit, Kliniken Essen-Mitte, Essen, Germany.

[20 ]Department of Gynecology with Breast Center, Charité – Universitätsmedizin Berlin, Germany.

[21 ]American University of Beirut Medical Center, Beirut, Lebanon.

[22 ]Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.

[23 ]Novartis Ireland Limited, Dublin, Ireland.

[24 ]Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.

[25 ]Novartis Pharma AG, Basel, Switzerland.

[26 ]Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

[27 ]The University of Texas MD Anderson Cancer Center, Houston, Texas.

Author notes

[#]

Y.-S. Lu and S.-A. Im contributed equally to this article.

[* ] Corresponding Author: Yen-Shen Lu, Department of Oncology, National Taiwan University Hospital, No. 7 Zhongshan South Road, Taipei City, Taiwan. Phone: 8862-2312-3456, ext. 67513; E-mail: yslu@ 123456ntu.edu.tw

Author information

Yen-Shen Lu https://orcid.org/0000-0001-7461-1291

Seock-Ah Im https://orcid.org/0000-0002-5396-6533

Marco Colleoni https://orcid.org/0000-0002-5743-3013

Fatima Cardoso https://orcid.org/0000-0002-6692-2249

Nadia Harbeck https://orcid.org/0000-0002-9744-7372

Keun Seok Lee https://orcid.org/0000-0001-5575-836X

Saul Campos-Gomez https://orcid.org/0000-0002-1804-2589

Kyung Hae Jung https://orcid.org/0000-0002-1580-7224

Michelino De Laurentiis https://orcid.org/0000-0001-9009-1572

Sherko Kuemmel https://orcid.org/0000-0001-9355-494X

Nagi El-Saghir https://orcid.org/0000-0001-9612-4224

Yan Ji https://orcid.org/0000-0001-9569-0574

Debu Tripathy https://orcid.org/0000-0002-5711-2404

Article

Publisher ID: CCR-21-3032

DOI: 10.1158/1078-0432.CCR-21-3032

PMC ID: 9377723

PubMed ID: 34965945

SO-VID: 083ba9fb-7651-4eb3-ba66-7411cede5c77

License:

This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

History

Date received : 01 September 2021

Date revision received : 24 November 2021

Date accepted : 21 December 2021

Page count

Pages: 9

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