Ribociclib: SABCS 2022 Phase II RIGHT Choice Trial in Breast Cancer
What is the RIGHT Choice ribociclib clinical trial as opposed to current clinical practice standards? So for aggressive disease status, conventionally, doctors (healthcare professional) will try to prescribe chemotherapy instead of initial endocrine therapy based regimen. So for postmenopausal patients, single aging chemotherapy is preferred, But for premenopausal patients, doctors will consider that some of them have a more aggressive tumor biology, so the tumor may grow faster. Secondly, the patient may be more tolerant of the side effects of combination chemotherapy. So that is why combination chemotherapy is frequently prescribed for the treatment of aggressive premenopausal HR+ (receptor HR positive human), HER2 negative advanced breast cancer, and with this ribociclib clinical trial, we prove that ribociclib plus endocrine therapy provides overall suppression. This is a typical treatment for premenopausal disease, and by showing a very high response, it is very similar to combination chemotherapy, with a longer progression-free survival, a similar time to response, and a lower toxicity. This study just demonstrated that in the future, the treatment of choice should be changed from combination chemotherapy to ribociclib plus endocrine therapy, plus ovary suppression in aggressive premenopausal patients with HR+ HER2 negative disease.
This is a phase II randomized study. We enrolled premenopausal women with HR+, HER2 negative advanced breast cancer with aggressive clinical features defined by the PI who think combination chemotherapy is clinically indicated. So what kind of disease status they will consider combination chemotherapy will be indicated, which may include symptomatic visceral metastasis, rapid disease progression, marked disease, or symptomatic non visceral disease. This is a first line treatment trial of ribociclib, so no prior systemic therapy was allowed. So we have a total of 222 patients enrolling to receive either ribociclib plus endocrine therapy, plus ovarian suppression or physician choice combination chemotherapy, which included docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine. The primary endpoint was progression-free survival. The key secondary endpoints included time to start treatment, failure, overall response rate, time to response, overall survival, and safety.
We choose progression-free survival as a primary endpoint. That is because at the very beginning of the ribociclib clinical trial design, we found. The response rate will be identical between the two arms. So it is quite impossible to do a non-inferiority design or equivalent design for this hard to treat population; it would need a lot of patients. However, according to a lot of trial results, we are quite sure. The progression free survival will be longer with ribociclib plus endocrine therapy compared to combination chemotherapy. And it is also meaningful because that it just means that patients don’t need to change to other chemotherapy frequently due to disease progression. So safety, other things important that progression-free survival is also important.
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What Was The Primary Endpoint For The RIGHT Choice Clinical Trial Of Ribociclib?
According to our primary endpoint, with a hazard ratio of .54 and the P value of .0007, ribociclib plus endocrine therapy as first line provides a significant PFS benefit of one additional year more than combination chemotherapy. So it just means that it provides a greater chance, of less chance of the 46% to have a disease progression or sudden death with ribociclib first line compared with combination chemotherapy. Many doctor (healthcare professional) came to you chemotherapy in patient with high tumor burden or aggressive disease status. The key problem is that you are not very well trained to consider which kind of patient is in critical status or not. So a lot of data, just overuse of the combination chemotherapy for any patient have multiple liver meds, they starting treatment, use combination chemotherapy. But this study just shown that either patient with vaso crisis, either tumor, patient with high tumor burden, or. The physician consider combination chemotherapy is indicated. You can use ribociclib plus endocrine therapy instead, and the end of day response rate are similar, the progression-free survival is longer, so it will help the doctor (healthcare professional), especially the last experience doctor, just easily to apply the treatment of choice for our patients. So I think that would be a practice changing study result and help the, especially the guideline maker to have a more able to communicate with the doctors (healthcare professional) because that nowadays their suggestion have evidence. Right choice study, now the results has clearly showed that in vast majority of the patient, whenever they have a high tumor burden or rapid disease progression, or even visual crisis, ribociclib plus endocrine therapy should be a preferred choice as compared with combination chemotherapy. But just one caution that in this study we have the limitation of that we recruit patient with PD rumin level, no more than 1.5 upper normal limit, so for them because the dose modification plan would be difficult either in chemotherapy arm or ribociclib arm. Then when you try to treat this patient, a close monitoring plan is mandatory.
5 Key Point of the RIGHT Choice Ribociclib Clinical Trial
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A large proportion of breast cancer patients in Asia-Pacific (42%) and the Middle East (50%) are 50 years of age or younger.
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Due to the lack of direct evidence, trials are required to compare the efficacy of ET in combination with CDK4/6 inhibitor versus CT in aggressive or high tumor burden settings where CT is clinically indicated for pre-/perimenopausal advanced breast cancer.
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Pregnancy, breastfeeding, and menopausal state are exclusion factors. Patients will be randomly assigned to receive ribociclib (600 mg, 3 weeks on/1 week off) in combination with letrozole or anastrozole with goserelin, or investigator’s choice of combination chemotherapy (docetaxel + capecitabine, paclitaxel + gemcitabine, or capecitabine + vinorelbine).
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Primary outcome measure is progression-free survival. Time to treatment failure, overall response rate, clinical benefit rate, time to response, overall survival, patient global health status, and safety are secondary endpoints. Utilization of healthcare resources will be studied as an exploratory endpoint.
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Taking ribociclib (tablets), ribociclib belongs to the class of drugs known as kinase inhibitors. It functions by inhibiting the action of an aberrant protein that instructs cancer cells to proliferate. This helps slow or stop the spread of cancer cells. And is used in combination to treat certain types of hormone receptor positives.
Yen-Shen Lu, MD – About The Author, Credentials, and Affiliations
A Clinical Professor of Medicine at the National Taiwan University College of Medicine and Division Chief of Medical Oncology at the National Taiwan University Hospital’s Department of Oncology in Taipei, Taiwan. Dr. Lu earned his medical degree from Chinese Medical College in Taichung in 1992 and his doctorate from National Taiwan University in Taipei in 2006. He has substantial expertise as a clinical trial initiator, protocol writer, clinical trial steering committee member/chair, and as the primary investigator or co-principal investigator for more than 70 clinical trials, with a focus on targeted medicines in metastatic breast cancer. He has been an invited speaker at a number of international conferences, including the Oncology Lead Summit, ESMO Asia, and the Global Breast Cancer Conference. He received the Scholar in Training Award at the 92nd Annual Meeting of the American Association for Cancer Research in 2001, and the Chien-Tien Hsu’s Outstanding Cancer Research Award in 2019. In addition, he directed a series of investigations concerning the epidemiology, biology, and genetic differences between Asian and Western breast cancer in young women. He is the author and co-author of over 90 articles published in international peer-reviewed journals, including Lancet Oncology, Clinical Cancer Research, Journal of the National Cancer Institute, and Journal of Clinical Oncology.
References
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ClinicalTrials.gov – Study to Compare the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Combination Chemotherapy in Premenopausal or Perimenopausal Patients With Advanced or Metastatic Breast Cancer (RIGHT Choice). ClinicalTrials.gov, October 25, 2022
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Medline Plus – Ribociclib. Medline Plus Ribociclib, December 15, 2020