Breakthrough for Women With Advanced Breast Cancer - Monaleesa Clinical Trial

The Saudi Oncology Association together with Novartis announced the outcomes of the groundbreaking MONALEESA Clinical Trials done women with advanced stages of breast cancer.

The women participating in the trial exhibited clinically meaningful improvement in pain symptoms as early as eight weeks; this improvement was sustained1. They benefited for a longer time until health-related quality of life (QoL) deterioration compared to those taking endocrine therapy alone1

Commenting on the clinical trials, Dr. Um Al Khair Abu Al Khair Commenting on the clinical trials, Adult Oncology Consultant at King Abdul Aziz Medical City, National Guard in Riyadh Dr. Um Al Khair said, “Breast cancer is No.1 type of cancer influencing women after thyroid cancer, and that 30% of cancer cases spread during the medical follow-up, with 16-20% of cases are diagnosed after reaching stage 4. But, what worsens the situation is that many physicians tend to employ chemotherapy at early stages, or after a single line of hormone therapy, beside the fact that many cases are diagnosed before menopause, and 20% are diagnosed before the age of 40.”

Premenopausal breast cancer is biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old3, 4

She stressed, “The selection of the right hormonal therapy is very critical to ensure positive results. The MONALEESA-7 clinical trials have focused on the premenopausal age group – The group that we need to identify its response to the medicine as it dominates up to 16% of all female cases. The study shows that the use of CDK inhibitors together with hormonal therapy after administering ovary suppression injection proved to be effective and could be used with postmenopausal patients, Dr. Um Al Khair added.

The treatment of breast cancer has been evolving very quickly over the last ten years with introduction of new medications as well as better understanding of knowledge of the disease.

“The understanding of breast cancer and how to treat it is setting an excellent example to other cancer sites to follow. The treatment options available for breast cancer today are directed to cancer cells based on their biological origin and behavior” explained Prof. Ahmed Ali Saad Al-Din Consultant Clinical Oncology, Department of Adult Oncology, King Abdul-Aziz Medical City, National Guard Health Affairs in Riyadh.

“Breast cancer is divided into three main subtypes: the most common one we call luminal type which is hormonal dependent. For each of these subtypes, a significant improvement has been made in both understanding and ways of treatment.”

The Luminal type of breast cancer is the most common which is brought by excessive hormonal exposure that is why hormonal therapy is the main way to treat this tumor. For a number of years hormonal therapy has shown good results in terms of survival and quality of life.

He added “it remains a challenge, a good number of patients who either fail to respond to this hormonal therapy because of what we call primary hormonal resistant tumors or those that develop resistance to such therapy along the way. In MONALEESA-7, the drug was used in pre-menopausal women which is the first phase 3 trial addressing this in pre-menopausal women, a section of patients who are relatively common in our society as the median age for breast cancer patients our region is 48 which is almost 10 years younger than what have been observed in the western countries.”

Prof Miteb Al Fohedi, Medical Oncology Consultant – Breast Cancer Sub-specialty at Princess Nourah Oncology Center Western Oncology Group Director at the Saudi Oncology Society explained “CDK 4/6 inhibitors have recently taken the forefront of the cancer landscape when it comes to hormone-positive breast cancer. Oral Highly selective CDK Inhibitors represent an important therapeutic advancement in breast cancer oncology, and we are happy that is now approved in Saudi. However, there are still some challenges in the optimization of CDK inhibits in clinical practice. There is a lack of predictive biomarkers to screen the appropriate population who can benefit most from these

Prof Saad adin closed by saying “As doctors, we are very happy to see a breakthrough for our patients. This is a real breakthrough in the management of care for this type of patients. However, the results that have been seen in MONALEESA-7 and similar trials have not been observed for a very long time. We strongly encourage that patients should be aware these aspects and physicians should also seriously consider he course of treatment explored with this clinical trial and apply therapy clear guideline to avoid unnecessary use to try and minimize the financial toxicity of the combination therapy.

Novartis plans to discuss MONALEESA-7 data with global health authorities worldwide.

Dr. Amr Saleh, General Manager, Novartis Oncology KSA added; “The Novartis Commitment to Patients and Caregivers defines what patients and caregivers can expect from Novartis. Better understanding patients’ needs and perspectives can allow us to make better medicines and support the work of healthcare professionals.”

We are pleased to see new breakthrough combination therapy provide strong efficacy and prolonged quality of life with pain reduction approved in KSA, and look forward to working with health authorities to bring a new treatment option to premenopausal or perimenopausal women,”

About MONALEESA-7

MONALEESA-7 is a Phase III randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of ribociclib in combination with tamoxifen or a non-steroidal aromatase inhibitor plus goserelin versus tamoxifen or an aromatase inhibitor plus goserelin, in premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer who had not previously received endocrine therapy for advanced disease. More than 670 women ranging from 23-58 years in age were randomized in the MONALEESA-7 trial. The first patient assessment occurred at eight weeks; separation of the PFS curves at this time was not a pre-specified endpoint of the study.

About Kisqali® (ribociclib)
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was approved by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali is not currently approved for use in premenopausal patients. 

Kisqali is approved for use in 44 countries around the world, including the United States and European Union member states. Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About the Kisqali Clinical Trial Program
With more than 2,000 patients, the MONALEESA program is the largest Phase III clinical program researching use of a CDK4/6 inhibitor in advanced breast cancer1.

The MONALEESA-7 findings add to the body of evidence from MONALEESA-2 supporting the benefit of Kisqali plus hormone therapy in first-line treatment of HR+/HER2- advanced or metastatic breast cancer. Novartis is continuing to evaluate Kisqali in combination with multiple hormonal therapies across a broad range of patients, including in the adjuvant setting.

MONALEESA-2 is a Phase III global registration trial evaluating Kisqali in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for their advanced breast cancer.

MONALEESA-3 is a Phase III study evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone in postmenopausal women or men with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. MONALEESA-3 is fully enrolled.

CompLEEment-1 is an open-label, multicenter, Phase IIIb study evaluating the safety and efficacy of Kisqali plus letrozole in men and pre- or postmenopausal women with HR+/HER2- advanced breast cancer who have not received prior hormonal therapy for advanced disease. CompLEEment-1 is enrolling.

The safety and efficacy of Kisqali with endocrine therapy as adjuvant therapy in premenopausal and postmenopausal women who have not previously received treatment with a CDK4/6 inhibitor is also being evaluated in the EarLEE-1 study, which is enrolling.

More information about these studies can be found at www.ClinicalTrials.gov.

About Novartis in Advanced Breast Cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in collaboration with the global community. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.

Important Safety Information from the Kisqali EU SmPC

The most common ADRs and the most common grade 3/4 ADRs (reported at a frequency ≥20% and ≥2% respectively) for which the frequency for Kisqali plus letrozole exceeds the frequency for placebo plus letrozole were blood and lymphatic system disorders (including abnormally low neutrophil and white blood cell count), headache, back pain, nausea, fatigue, diarrhea, vomiting, constipation, hair loss and rash and abnormally low levels of neutrophils or white blood cells, abnormal liver function tests (increased alanine and aspartate aminotransferase), abnormally low lymphocyte count, low levels of phosphate, vomiting, nausea, fatigue and back pain, respectively. Low levels of neutrophils was the most commonly seen severe adverse event; fever in addition to a low neutrophil count was reported in 1.5% of patients.

Kisqali can cause serious side effects such as a significant decrease in neutrophil count, abnormal liver function tests and may have an effect on the electrical activity of the heart known as QT/QTc interval prolongation, which could lead to disturbances in heart rhythm. As a precaution, patients should have complete blood counts, liver function, and serum electrolyte levels measured prior to starting treatment as well as during treatment with Kisqali. Patients should also have their heart activity checked before and monitored during treatment.

The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease.

The use of Kisqali with medicinal products known to prolong QTc interval or strong CYP3A4 inhibitors should be avoided as this may lead to prolongation of the QT/QTc interval. If treatment with a strong CYP3A4 inhibitor cannot be avoided, the Kisqali dose should be reduced. Concomitant administration with other medicines that could affect cardiac repolarization or prolong the QT/QTc interval should be taken into account prior to and during treatment with Kisqali. Patients taking sensitive CYP3A4 substrates with narrow therapeutic index should use caution because of the increased risk of adverse events that may occur if these medications are co-administered with Kisqali.

Kisqali contains soya lecithin and therefore it should not be taken by patients who are allergic to peanut or soya.

Animal studies suggest that Kisqali may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Kisqali during treatment and up to 21 days after stopping treatment. Women should not breast feed for at least 21 days after the last dose of Kisqali. Kisqali may affect fertility in males.

Please see full Prescribing Information for Kisqali, available at www.kisqali.com.

Disclaimer

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