Novartis (NVS) to Stop Trial on Breast Cancer Drug Early

cp418

http://www.zacks.com/stock/news/217833/novartis-nv...

Novartis (NVS) to Stop Trial on Breast Cancer Drug Early

https://www.novartis.com/news/media-releases/monal...

JohnSmith

This is about the MONALEESA-2 Phase III clinical trial evaluating the CDK 4/6 drug LEE011 (Ribociclib). It ended early as the independent data monitoring committee confirmed that an interim analysis showed the study had hit the primary endpoint for progression-free survival.
Full details will be released at the 2016 ASCO conference in a couple weeks.
This CDK4/6 inhibitor is similar to Palbociclib (Ibrance). It targets aberrant cell cycle involved in cell replication. Overactive CDK 4 and 6 helps the cancer to accelerate, and checking that activity can rein it back in.

Here's the original trial info:
"A Randomized Double-blind, Placebo-controlled Study of LEE011 in Combination with Letrozole for the Treatment of Postmenopausal Women with ER+, HER2-, Advanced Breast Cancer who received no prior therapy for advanced disease"
Enrollment: 667
Study Start Date: December 2013
Estimated Study Completion Date: August 2019

Longtermsurvivor

ASCO abstract here on upcoming trial here:

https://community.breastcancer.org/forum/8/topics/...

JohnSmith

The ESMO 2016 Oncology conference in Copenhagen, Denmark is happening this weekend.
ESMO = European Society for Medical Oncology
www.esmo.org/Conferences/ESMO-2016-Congress

Interim results about the MONALEESA-2 trial (NCT01958021) were just released. Here's the Abstract:

ABSTRACT: LBA1_PR - First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC)
Source: https://cslide.ctimeetingtech.com/library/esmo/browse/search/7eJ#2z94z024f

Background: Endocrine therapy (ET) is an established first-line treatment for ABC. However, ET resistance and disease progression eventually occur in most patients. Cyclin-dependent kinase (CDK) 4/6 inhibition is a valid treatment strategy for HR+ ABC and may help overcome or delay ET resistance. Here we report interim results from MONALEESA-2 (NCT01958021), a double-blind, randomized, phase 3 trial evaluating the efficacy and safety of first-line ribociclib (a selective CDK4/6 inhibitor) + letrozole in women with HR + , HER2– ABC.

Methods: Postmenopausal women (N = 668) with HR + , HER2– ABC with no prior systemic treatment for ABC were randomized (1:1) to receive ribociclib (600 mg/day, 3-weeks-on/1-week-off) + letrozole (2.5 mg/day, continuous) or placebo + letrozole. The primary endpoint was locally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS; key secondary endpoint), overall response rate (ORR), clinical benefit rate (CBR), and safety. A pre-planned interim analysis was conducted after 243 PFS events (information fraction 80%) had occurred.

Results: Baseline patient characteristics were balanced between treatment arms. The study met its primary objective: at the interim analysis (data cut-off Jan 29, 2016), PFS was significantly improved in the ribociclib arm, with a hazard ratio of 0.556 (95% CI: 0.429–0.720; p = 0.00000329). Median PFS was not reached in the ribociclib arm (95% CI: 19.3–not estimable) vs 14.7 months in the placebo arm (95% CI: 13.0–16.5). In patients with measurable disease at baseline, ORR was 53% vs 37% (ribociclib vs placebo arm; p = 0.00028) and CBR was 80% vs 72% (p = 0.02). Common Grade 3/4 adverse events (≥5% of patients; ribociclib vs placebo arm) were neutropenia (59% vs 1%), leukopenia (21% vs 1%), hypertension (10% vs 11%), elevated alanine aminotransferase (9% vs 1%), lymphopenia (7% vs 1%), and elevated aspartate aminotransferase (6% vs 1%). OS data were immature at data cut-off.

Conclusions: Ribociclib + letrozole was well tolerated and significantly prolonged PFS vs letrozole alone in postmenopausal women with HR+, HER2- ABC who had received no prior therapy for ABC.

NOTE: PFS data is nice, but it's the Overall Survival (OS) data that really counts. The OS data will take some time to mature since the trial is slated to end in ~Aug 2019.

exbrnxgrl

Very interesting as I did a 1 hour video conference (this past Thursday) that appears to seek patient feedback on potential literature for patients who may be interested in this drug. I had to read quite a few passages regarding this drug, who it might benefit, it's efficacy, the mechanism by which it works etc. and was then asked very specific questions about what was important to me and why. Interestingly, none of the passages were about side effects. The interviewer was very clear about the fact that she did not work for the drug, nor did she or her company have any personal stake in drug or it's development.

BarredOwl

Here is an OncLive feature regarding the MONALEESA-2 trial results disclosed at the ESMO 2016 conference:

OncLive (2016): http://www.onclive.com/conference-coverage/esmo-2016-congress/ribociclib-leads-to-major-pfs-increase-in-hr-metastatic-breast-cancer

The OncLive feature mentioned simulatneous publication of results on-line in the New England Journal of Medicine, which I believe is this article:

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

Hortobagyi (Oct. 8, 2016): http://www.nejm.org/doi/full/10.1056/NEJMoa1609709?query=featured_home

The full-text page includes access to Supplementary Material (Protocol; Supplementary Appendix; Disclosure Forms), plus a link to a pdf version of the article:

PDF version: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1609709

BarredOwl

Longtermsurvivor

Here's the press release, or as I refer to them, a free advertisement that will reach the media and us the viewers and listeners. It will be many years before Overall Survival (OS) is available. We still haven't received it from the palbociclib/Ibrance trials and that drug is widely used in MBC.

Best healing wishes all, Stephanie

xox

RIBOCICLIB IMPROVES PROGRESSION-FREE SURVIVAL FOR WOMEN WITH METASTATIC BREAST CANCER

Findings simultaneously presented at ESMO, published in New England Journal of Medicine

Released: 7-Oct-2016 4:05 PM EDT

Source Newsroom: University of Texas M. D. Anderson Cancer Center

CITATIONS

New England Journal of Medicine

KEYWORDS

Newswise — Copenhagen, Denmark – In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, ribociclib, in combination with the aromatase inhibitor letrozole, dramatically improved progression-free survival (PFS) of post-menopausal women with hormone receptor-positive metastatic breast cancer, compared to the hormone therapy alone.

The study found a 44 percent improvement in PFS with ribociclib, a CDK4/6 inhibitor, and letrozole as a front line therapy. Gabriel Hortobagyi, M.D., professor of Breast Medical Oncology, presented the findings at ESMO 2016 Congress, and is the corresponding author of the New England Journal of Medicine paper.

According to the American Cancer Society, 246,660 women will be diagnosed with breast cancer in 2016, and 40,450 women will die from the disease. More than two-thirds of all breast cancers are hormone dependent, says Hortobagyi.

"These findings have the potential to impact tens of thousands of women each year," says Hortobagyi, the study's principal investigator. "At some point, all breast cancers become resistant to endocrine therapy, so reversing, preventing or delaying that resistance is a major unmet need in this population.

"Women with metastatic disease will be on some therapy for the rest of their lives, and it's paramount that we delay the progression of their disease for as long as possible," continues Hortobagyi.

The international double-blind study, MONALEESA-2, enrolled 668 post-menopausal women with advanced breast cancer at 223 trial sites in 29 countries. They were randomized to receive either ribociclib and letrozole, or letrozole and placebo. None had been previously treated for their advanced disease.

The study's primary endpoint was PFS; secondary endpoints included overall survival, overall response rate (ORR) and safety. The median follow up of patients was 15.3 months.

The median PFS was not reached in the study arm at data cut-off, compared to 14.7 months in the placebo arm. In those with measurable disease who received ribociclib, the ORR was 52.7 percent, compared to 37.1 percent in those who received letrozole alone.

Serious adverse events occurred in less than five percent of patients overall, but side effects were higher in the ribociclib arm, including neutropenia (59 percent vs, 1 percent) and leukopenia (21 percent vs. 1 percent). Most could be managed through dose interruption and reduction, says Hortobagyi. The discontinuation rate of the investigative drug was 7.5 percent, compared to 2.1 percent in the placebo cohort.

These findings could represent a paradigm shift in the future medical management of this patient population.

"When I started my career at MD Anderson in the 1970s, the median survival for women with metastatic breast cancer was just under two years. Now, with this discovery and other advances in the field, we can increasingly treat this as a chronic disease," says Hortobagyi. "Also, because we are able to delay or avoid chemotherapy, the quality of these women's lives has improved dramatically."

As follow-up, adjuvant trials with ribociclib are now being designed, says Hortobagyi. Ribociclib will also be studied in younger, pre-menopausal women with breast cancer.

Ribociclib is developed by Novartis, who also sponsored the trial. The drug received Breakthrough Therapy Designation by the Food and Drug Administration in August 2016.
Regarding relevant disclosures, Hortobagyi receives research support from Novartis and has served as a consultant.

In addition to Hortobagyi, other authors on the study include: Salomon M. Stemmer, M.D., Davidoff Center, Rabin Medical Center, Tel Aviv University; Howard A. Burris, M.D., Sarah Cannon Research Institute; Yoon-Sim Yap, MBBS, National Cancer Centre Singapore; Gabe S. Sonke, M.D., Ph.D., Netherlands Cancer Institute and BOOG Study Center; Shani Paluch-Shimon, MBBS, Sheba Medical Centre; Mario Campone, M.D., Ph.D., Institut de Cancérologie de l'Ouest/René Gauducheau; Kimberly L. Blackwell, M.D., Duke University Medical Center; Fabrice André, M.D., Ph.D., Institut Gustave Roussy, Université Paris Sud; Eric P. Winer, M.D., Dana-Farber Cancer Institute; Wolfgang Janni, M.D., Ph.D., University of Ulm; Sunil Verma, M.D., Tom Baker Cancer Centre; Pierfranco Conte, M.D., University of Padova and Istituto Oncologico Veneto, IRCCS; Carlos L. Arteaga, M.D., Vanderbilt-Ingram Cancer Center; David A. Cameron, M.D., Edinburgh Cancer Research Centre, University of Edinburgh; Katarina Petrakova, M.D., Ph.D., Masaryk Memorial Cancer Institute; Lowell L. Hart, M.D., Florida Cancer Specialists/Sarah Cannon Research Institute; Cristian Villanueva, M.D., University Hospital of Besançon; Arlene Chan, M.D., Breast Cancer Research Centre – Western Australia and Curtin University; Erik Jakobsen, M.D., Department of Oncology, Vejle Hospital; Arnd Nusch, M.D., Onkologische Praxis; Olga Burdaeva, M.D., Arkhangelsk Clinical Oncology Dispensary; Eva-Maria Grischke, M.D., University of Tübingen; Emilio Alba, M.D., Ph.D., Hospital Universitario Virgen de la Victoria, IBIMA; Erik Wist, M.D., Ph.D., Oslo University Hospital; Norbert Marschner, M.D., Joint Practice for Interdisciplinary Oncology and Hematology; Anne M. Favret, M.D., Virginia Cancer Specialists; Denise Yardley, M.D., Sarah Cannon Research Institute, Tennessee Oncology, Thomas Bachelot, M.D., Ph.D., Centre Léon Bérard; Ling-Ming Tseng, M.D., Taipei Veterans General Hospital, National Yang-Ming University; Sibel Blau, M.D., Rainier Hematology-Oncology, Northwest Medical Specialties; Fengjuan Xuan, Ph.D., Michelle Miller, Caroline Germa, M.D., Samit Hirawat, M.D., all of Novartis Pharmaceuticals Corporation; Farida Souami, Novartis Pharma AG; and Joyce O'Shaughnessy, M.D., The US Oncology Network.

Longtermsurvivor

Important article on the difference between relative and absolute risks.

https://community.breastcancer.org/forum/73/topics...

If you have the stamina or interest, read Gerd Gigenzer's work on understanding risk and statistics. Great for the common reader.

healing regards, Stephanie