Breast Cancer Research and Treatment

, Volume 169, Issue 3, pp 469–479 | Cite as

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2− advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial

  • Wolfgang Janni
  • Emilio Alba
  • Thomas Bachelot
  • Sami Diab
  • Miguel Gil-Gil
  • Thaddeus J. Beck
  • Larisa Ryvo
  • Rafael Lopez
  • Michaela Tsai
  • Francisco J. Esteva
  • Pilar Zamora Auñón
  • Zdenek Kral
  • Patrick Ward
  • Paul Richards
  • Timothy J. Pluard
  • Santosh Sutradhar
  • Michelle Miller
  • Mario Campone
Clinical trial



The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).


Postmenopausal women (N = 668) with HR+ , HER2− ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.


Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0–NR) in the RIB arm versus 18.6 months (95% CI, 14.8–23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.


RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2− ABC.


Ribociclib Advanced breast cancer MONALEESA-2 CDK4/6 



We thank the patients who participated in this trial and their families, as well as staff members at individual trial centers who provided support; Avinash Yerramsetti and Amol Hosing (Novartis Healthcare Pvt Ltd) for providing medical editorial assistance with this manuscript. Ribociclib was discovered by Novartis Institutes for BioMedical Research in collaboration with Astex Pharmaceuticals.


The study was initiated, funded, and sponsored by Novartis Pharmaceuticals Corporation. The study was designed by the investigators and the sponsor. Design and conduct of the study was undertaken by the sponsor in collaboration with investigators. The study investigators and their respective research teams collected the data; Novartis Pharmaceuticals Corporation compiled the data for summation and analysis. All authors were responsible for data interpretation. The article was prepared by Dr Janni in conjunction with all the authors, including employees of the sponsor. The corresponding author had final responsibility for the decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

Dr. Janni reports grants and personal fees from Novartis during the conduct of the study and outside the submitted work. Dr. Alba reports advisory board fees from Roche, Pfizer, and Novartis outside the submitted work. Dr. Bachelot reports personal fees from AstraZeneca, Roche, Novartis, and Pfizer; research grants from Roche, Novartis, and Pfizer outside the submitted work. Dr. Esteva reports consulting fee and research funding to his institution. Dr. Pluard reports advisory board fees from Novartis. Mr. Sutradhar is an employee of Novartis Pharmaceutical Corporation. Dr. Miller is employee of Novartis Pharmaceutical Corporation and hold Novartis stock options. Prof. Campone reports fees for advisory boards from Novartis, during the conduct of the study; and fees for advisory boards from Lilly, Sanofi, Pfizer, and AstraZeneca outside the submitted work. Dr. Diab, Dr. Gil, Dr. Beck, Ryvo, Dr. Tsai, Dr. Aunon, Dr. Kral, Dr. Ward, and Dr. Richards have nothing to disclose.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wolfgang Janni
    • 1
  • Emilio Alba
    • 2
  • Thomas Bachelot
    • 3
  • Sami Diab
    • 4
  • Miguel Gil-Gil
    • 5
  • Thaddeus J. Beck
    • 6
  • Larisa Ryvo
    • 7
  • Rafael Lopez
    • 8
  • Michaela Tsai
    • 9
  • Francisco J. Esteva
    • 10
  • Pilar Zamora Auñón
    • 11
  • Zdenek Kral
    • 12
  • Patrick Ward
    • 13
  • Paul Richards
    • 14
  • Timothy J. Pluard
    • 15
  • Santosh Sutradhar
    • 16
  • Michelle Miller
    • 16
  • Mario Campone
    • 17
  1. 1.University of UlmUlmGermany
  2. 2.Hospital Universitario Virgen de la Victoria, IBIMAMálagaSpain
  3. 3.Centre Léon BérardLyonFrance
  4. 4.Rocky Mountain Cancer CentersAuroraUSA
  5. 5.Institut Català d’Oncologia, IDIBELL, L’Hospitalet de LlobregatBarcelonaSpain
  6. 6.Highlands Oncology GroupFayettevilleUSA
  7. 7.Tel Aviv Sourasky Medical CenterTel AvivIsrael
  8. 8.Hospital Clínico Universitario e Instituto de Investigación Santiago-CIBERONCA CoruñaSpain
  9. 9.Minnesota OncologyMinneapolisUSA
  10. 10.Perlmutter Cancer Center at New York University Langone HealthNew YorkUSA
  11. 11.Hospital Universitario La PazMadridSpain
  12. 12.Department of Internal Medicine, Hematology and OncologyUniversity Hospital BrnoBrnoCzech Republic
  13. 13.Oncology Hematology CareKenwoodUSA
  14. 14.Oncology Hematology Associates of Southwest VirginiaRoanokeUSA
  15. 15.Saint Luke’s Health SystemKansas CityUSA
  16. 16.Novartis Pharmaceuticals CorporationEast HanoverUSA
  17. 17.Centre René Gauducheau, Institut de Cancérologie de l’OuestSaint-HerblainFrance

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