is responsible for
numerous deaths among women all over the world. With increased awareness,
regular screening and effective treatments, several women diagnosed early go on
to lead normal lives.
‘Ribociclib and Letrozole combination for advanced breast cancer can prolong patient survival.’
cancer is still difficult to be completely cured at an advanced stage. Advanced
breast cancer includes stage 3 cancer that has spread locally, for example, to
the chest wall, skin or local lymph nodes, and stage 4 cancer, that has spread
to distant sites like the brain, bones and the liver. Under such circumstances,
efforts are made to prevent progression of the cancer and prolong the life of
Breast cancer is treated
Patients can develop resistance to hormonal treatment, thereby
making treatment ineffective
- Surgery, which
may be just removal of the lump or the entire breast
- Radiation therapy
treatment, which is useful for those cancers that are positive for hormone
receptors i.e. estrogen and /or progesterone receptors. (ER-positive
and/or PR-positive). Hormonal treatments for breast cancer include:
- The estrogen
receptor blockers tamoxifen and fulvestrant
inhibitors that reduce production of estrogen which include letrozole, anastrozole and exemestane
- Suppression of
ovarian function with either surgical removal or the ovaries, use of LHRH
agonists leuprolide or goserelin, or chemotherapy drugs
- Targeted therapy,
It is used in the treatment of HER2-positive breast cancers. HER2 or
HER2/neu is a protein on breast cancer cells that promotes the growth of
the cancer. Medications like trastuzumab, pertuzumab, ado-trastuzumab emtansine
and lapatinib act by targeting this protein.
. To overcome this
problem, ribociclib drug is being tried out.
Ribociclib belongs to group of drugs called selective cyclin
dependent kinase inhibitors. It acts on and inhibits two proteins called cyclin
dependent kinase 4 and 6 (CDK4/6), which promote the growth of cancer cells and
are responsible for the resistance to drugs like letrozole
. By inhibiting the pathway, it possibly prevents the resistance and
allows letrozole to be used for a longer period thereby delaying the use of
chemotherapy. Palbociclib is a similar drug that is already approved by the FDA
in HR+/HER- advanced breast cancers.
Drug Trial Conducted on Breast Cancer Patients
is being evaluated in the MONALEESA trial that is being conducted in breast
cancer patients all over the world.
The MONALEESA trial
includes the MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials.
In the MONALEESA-3
trial, the combination of ribociclib and fulvestrant is being tested, while in
the MONALEESA-7 trial, ribociclib is being tested for use along with endocrine
therapy and goserelin.
The MONALEESA-2 study included
668 patients with HR-positive, HER2-negative advanced breast cancer. Among
these, 334 patients received letrozole 2.5 mg/ day and a placebo, while the
remaining 334 patients were administered letrozole 2.5 mg/ day plus ribociclib
(in a regimen 600 mg /day for three weeks followed by a break for a week). The
patients were assessed every 8 weeks for the first year and a half, and then
every 12 weekly.
The researchers found that the combined treatment with ribociclib
and letrozole increased the progression-free survival of the patients by 44% as
compared to letrozole alone
. As mentioned above, letrozole is an aromatase inhibitor that reduces
the production of estrogen
. It is used in postmenopausal women with
hormone-positive breast cancer who have early received tamoxifen for 5 years.
A subgroup analysis of the
MONALEESA-2 trial in the Asian population is being presented at the European
Society of Medical Oncology 2016 Congress, Singapore. The analysis is relevant
since the incidence of breast cancer is high in several parts of Asia. Asia
accounts for 24% of all breast cancer cases, several of these being in the
advanced stages at the time of diagnosis.
The research team found that the combined treatment with ribociclib
and letrozole caused a significant improvement in progression-free survival in
Asian patients as compared to those who received only letrozole
. The safety of the combination was acceptable and similar to that
observed in the full population.
Side effects of ribociclib include reduced white blood cell counts
(neutropenia / leucopenia) and increase in the levels of liver enzymes
. The patient may thus be exposed to additional side effects.
However, it could still be useful if the benefits of the combination outweigh
Ribociclib and letrozole used
together may thus provide an alternative to the treatment of HR+/HER2- advanced
breast cancer in the Asian patients. However, the cost of the treatment may not
support the use of this drug in several parts of Asia.
Further studies to pinpoint
patients who would particularly benefit from the new drug, like those with a
specific biomarker, could help to better select patients for the treatment.
Novartis, the company
manufacturing ribociclib, has been granted Priority Review for the drug, which
means that the drug will go through the approval process faster and possibly
get approval early.References:
- LBA1_PR - 'First-line ribociclib + letrozole in postmenopausal Asian women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC): A subgroup analysis from MONALEESA-2' Presented by Yoon-Sim Yap during the Presidential Symposium at ESMO Asia 2016, Singapore.