Breast cancer

Ribociclib approved as first line therapy for advanced or metastatic breast cancer


The CDK4/6 inhibitor ribociclib (Kisqali) can now be used as first line therapy for pre and peri menopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer after the TGA approved expanded indications for the drug.

The new indication covers use of the drug in combination with a luteinizing hormone-releasing hormone (LHRH) agonist and an aromatase inhibitor (AI) in pre, peri or postmenopausal women, and with fulvestrant as first or second-line treatment in postmenopausal women.

The drug was initially approved in Australia last year as an initial endocrine-based therapy with an aromatase inhibitor combination for HR+/HER2 advanced or metastatic breast cancer in postmenopausal women.

The new indication for the combination in younger women makes ribociclib the first CDK4/6 inhibitor indicated for women regardless of their menopausal status.

The latest TGA approval comes after review of data from the MONALEESA-7 and MONALEESA-3 Phase III clinical trials. MONALEESA-7 focused on pre and perimenopausal women and MONALEESA-3 involved postmenopausal women.

Findings showed prolonged progression-free survival (PFS) and improvements within eight weeks after treatment with the ribociclib-based regimens, when compared to use of endocrine therapy alone.

Speaking to the limbic Professor Arlene Chan, medical oncologist at the Breast Cancer Research Centre in Perth, said the drug in combination with endocrine therapy is reported to have almost doubled the median PFS, compared to endocrine therapy alone, in the MONALEESA-7 trial.

In MONALEESA-3, the ribociclib and fulvestrant combination achieved a median PFS of 14.6 months compared to 9.1 months with fulvestrant alone in patients who had received up to one line of prior endocrine therapy for advanced disease.

Professor Chan, who is an investigator on the MONALEESA trials, said the findings from the phase III studies should be ‘practice changing’.

“We now have a non chemotherapy treatment that includes CDK inhibitors and endocrine treatment, which is producing incredibly effective and durable results so from that point of view we have substantially changed the way we manage patients with this type of metastatic cancer.”

A group of women who traditionally oncologists would recommend chemotherapy to in the first line metastatic setting, she pointed out.

“The knowledge of these results to oncologists should really essentially be practice changing in the sense that, on an individual basis, a high proportion of women will be able to avoid chemotherapy.”

Professor Chan says the new ribociclib indication ‘breaks the old approach’ of managing metastatic breast cancer particularly in patients with a substantial volume of cancer and with secondary cancers involving the liver and the lung.

“The teaching prior to the availability of the CDK4/6 inhibitors would be that chemotherapy would be considered the more effective treatment – both from the point of view that it is considered more effective for visceral disease and because one considers there is a time urgency to treat these patients.”

“But we now have very high level randomised clinical trial evidence that a lot of patients who have visceral disease, excluding patients in visceral crisis, should be very good candidates for CDK4/6 inhibitor therapy in the first instance,” she said noting that about 50-60% of women enrolled in the trials that evaluated CDK inhibitors in the first line setting had visceral metastases.

According to Professor Chan the most common adverse reactions in response to ribociclib in at least 20% of patients, were neutropenia, nausea, infections, fatigue, diarrhoea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.

She also said that certain drugs, such as macrolide antibiotics for instance, could interfere with the metabolism of the CDK4/6 inhibitor while a number of neurological drugs used in combination with ribociclib have been associated with the QT interval prolongation.

“It’s important that oncologists inform the general practitioner that patients are on ribociclib and to be cognisant of certain drugs that they should avoid prescribing.” Professor Chan cautioned.

Ribociclib is currently reimbursed on the Pharmaceutical Benefits Scheme (PBS) in combination with an AI (anastrazole or letrozole) in postmenopausal women with hormone receptor HR+/HER2- locally advanced inoperable or metastatic breast cancer in the first line metastatic setting.

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