Recent international developments in breast cancer medicine approvals emphasise the need for a much broader range of medicines in New Zealand. Availability, combined with funding, would enable oncologists to choose the best medicines and combinations for individual patients, Breast Cancer Aotearoa Coalition (BCAC) says.
The US Food and Drug Administration has approved the use of ribociclib (Kisqali - Novartis) in combination with an aromatase inhibitor for premenopausal and perimenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine-based therapy.
The FDA said in a media release it had also approved ribociclib in combination with fulvestrant for postmenopausal women with these forms of breast cancer, as initial endocrine-based therapy or following disease progression on endocrine therapy.
Ribociclib was previously approved by the FDA for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine therapy. In New Zealand, ribociclib hasn’t yet been submitted for Medsafe approval, and fulvestrant is currently under consideration by PHARMAC following an application from BCAC.
BCAC spokeswoman Louise Malone said ribociclib is a CDK 4/6 inhibitor, a group of medicines that prevent over-proliferation of cancer cells and improve progression free survival when added to existing therapies.
Another CDK 4/6 inhibitor is palbociclib (Ibrance), which is registered in New Zealand by Medsafe and is currently being considered for funding by PHARMAC. A petition calling for Ibrance funding currently has more than 21,800 signatures and will be presented to Parliament by organiser Terre Nicholson, Metavivors New Zealand and BCAC.
Ibrance is a new medicine for treating advanced oestrogen-receptor-positive, HER2-negative breast cancer. It was approved by the FDA in 2015, in combination with Femara (letrozole). The PALOMA-2 clinical trial showed that adding Ibrance to letrozole on average increased the time to progression of the cancer to 24.8 months compared to 14.5 months in those who took letrozole alone.
“These FDA decisions highlight the value in having a variety of medicines available to use in combinations,” Louise said.
“This is especially important in New Zealand, where the slow progress of new medicines through our approval and funding processes means that the most effective new combinations of medicines needed by breast cancer patients are not always available to them.”
“We would urge PHARMAC to consider this latest decision by the FDA because it shows the tremendous benefits of providing effective medicines and also combinations of medicines to the women who need them”.
PHARMAC's September meeting of its cancer specialist advisory committee will be considering at least 5 important breast cancer medicines. These are trastuzumab-emtansine (Kadcyla), palbociclib (Ibrance), fulvestrant (Faslodex), nab-paclitaxel (Abraxane) and pertuzumab (Perjeta). “These medicines are needed for different sub-types of breast cancer and oncologists should be able to choose the most effective sequences and combinations for each of their individual patients. Breast cancer has no “one size fits all” solutions. Oncologists need access to the full toolkit to deliver the best results and ensure their patients have the best possible length and quality of life”.
The FDA says its latest ribociclib approval is the first approval using the US Real Time Oncology Review and the Assessment Aid, pilot programmes that enabled the FDA review team to begin analysing data before the application submission. The FDA was able to approve the application less than one month after it was submitted.
BCAC recently made a submission to New Zealand’s PHARMAC consultation on how it could better incorporate the consumer voice in its decision making. Among other recommendations, BCAC called for a more streamlined decision making structure and processes to improve timeliness of decisions and give greater certainty to oncologists and patients.
Australia
Ribociclib was listed this year, from 1 July 2018, on Australia’s Pharmaceutical Benefits Scheme, a government scheme that gives more affordable access to vital medicines. The listing means eligible women will pay up to A$500 a month instead of approximately A$5000 for the medicine. The lower cost applies to Australians and eligible visitors for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced inoperable or metastatic breast cancer. Breast Cancer Network Australia says the new rate applies to people who have not already been treated with a hormone-blocking agent for metastatic breast cancer.
FDA information on the research behind the ribociclib approval:
Ribociclib in combination with an aromatase inhibitor
The efficacy of ribociclib in combination with an aromatase inhibitor for pre/perimenopausal women was based on MONALEESA-7 (NCT02278120), a randomised, double-blind, placebo-controlled trial. Pre/perimenopausal women were randomised to ribociclib plus either a non-steroidal aromatase inhibitor (NSAI) or tamoxifen and goserelin versus placebo plus either an NSAI or tamoxifen and goserelin.
Results from the pre-specified NSAI-only subgroup of 495 pre/peri-menopausal women with HR-positive, HER2-negative, advanced breast cancer who received no prior endocrine therapy for advanced disease showed an estimated median progression-free survival (PFS, RECIST 1.1) of 27.5 months for patients on the ribociclib arm compared with 13.8 months for those on the placebo arm (HR 0.569; 95% CI: 0.436, 0.743). Ribociclib is not indicated for concomitant use with tamoxifen.
Efficacy of ribociclib in combination with fulvestrant
The efficacy of ribociclib in combination with fulvestrant was demonstrated in MONALEESA-3 (NCT02422615), a randomised double-blind, placebo-controlled trial of ribociclib in combination with fulvestrant in 726 postmenopausal women with HR-positive, HER2-negative, advanced breast cancer who received no or only one line of prior endocrine treatment. The estimated median PFS was 20.5 months for patients taking ribociclib compared with 12.8 months for those who received placebo (HR 0.593; 95% CI: 0.480, 0.732; p<0.0001).
The most common adverse reactions in at least 20% of patients were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.
The FDA noted that the recommended starting ribociclib dose is 600 mg orally (three 200 mg tablets) once daily with or without food for 21 consecutive days followed by 7 days off treatment.
2 August 2018
