Interview: More options in CDK4/6 inhibitor-Faslodex

Professor Kim Ji Yeon at Samsung Medical Center Hematology-Oncology Division

Ibrance relatively beneficial in adverse reaction, suitable for elderly patients

Kisqali only option for pre-menopausal patients, can avoid oophorectomy

Professor Kim Ji Yeon

The emergence of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in treatment of patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer has brought a change in treatment pattern.

 

Technically, chemotherapy was the only option in the hormone receptor-positive (HR+) and HER2- breast cancer.

 

Ibrance (palbociclib), the first CDK4/6 inhibitor to be approved in South Korea in 2016, was already under the limelight from the R&D phase, and it firmly took root in the therapeutic scene as the healthcare reimbursement was granted on the aromatase combination therapy in post-menopausal female patients as the first-line treatment in November 2017.

 

But still, there was an unmet medical needs—the Faslodex (fulvestrant) combination therapy as a second-line therapy.

 

Regardless of relentless attempts to receive the healthcare reimbursement, the indication is yet to be listed for over two years.

 

However, the restraint was lifted in last June.

 

Now, the patients can fully take advantage of the benefits from CDK4/6 inhibitor.

 

And as Verzenio (abemaciclib) and Kisqali (ribociclib) are either listed or to be listed soon, the patients have two more options besides Ibrance.

 

Daily Pharm interviewed Professor Kim Ji Yeon at Samsung Medical Center Hematology-Oncology division and heard her story of the prospects in utilizing CDK4/6 inhibitor.

 

-What is the significance in having the reimbursed option of Faslodex combination therapy?

 

As for a healthcare provider, more than anything, CDK4/6 inhibitor is an option that lessens the concern of ‘relapse.’ Up until recently, the healthcare coverage was limited to the aromatase combination therapy for the first-line treatment.

 

The reimbursement expanding to Faslodex combination therapy is providing benefits to more people, and healthcare providers are now treating the patients in peace.

 

Being able to prescribe a CDK4/6 inhibitor in combination with Faslodex in patients whose cancer advanced after a tamoxifen adjuvant treatment is a blissful option for patients.

 

-With the expanding coverage, follow-on drugs (Verzenio and Kisqali) have also won reimbursements.

 

Especially, soon-to-be-listed Kisqali even covers pre-menopausal female patients.

 

Which factors should patients consider when choosing a CDK4/6 inhibitor?

 

Surely, Kisqali would be prevalently used among pre-menopausal patients.

 

In the past, CDK4/6 inhibitor in combination with an aromatase inhibitor was the only option after prescribing tamoxifen adjuvant hormonal therapy following a bilateral salpingo-oophorectomy (BSO).

 

But now patients skip BSO and simultaneously use Kisqali plus aromatase inhibitor and gonadotropin releasing hormone (GnRH) agonist.

 

The healthcare providers also try to avoid BSO.

 

However, patients using Ibrance or Verzenio after having a BSO do not have to get injected every month.

 

Specifically, Ibrance is prescribed for two to three months’ worth at once as it rarely causes adverse reaction.

 

On the contrary, patients using Kisqali would have to visit hospital to get injected once a month.

 

-You have mentioned Ibrance is advantageous regarding adverse reaction.

 

Does that mean between various CDK4/6 inhibitors, there are differences in adverse reactions?

 

Apparently, the adverse reaction depends on whether the CDK4/6 inhibitor blocks ‘4’ or ‘6’ more, or other types of CDK including CDK2 or hinders cyclin activity.

 

Verzenio and Kisqali tend to frequently cause stomach related adverse reaction.

 

Patients usually complain about having diarrhea with Verzenio and having nausea or indigestion with Kisqali.

 

On the other hand, Ibrance has reported barely any adverse reaction related to stomach.

 

Nevertheless, reduction in neutrocyte and bone density, compared against Verzenio, were more frequently reported from Ibrance.

 

Moreover, Kisqali and Ibrance share similar level of hematological adverse reaction like the reduction in neutrocyte.

 

For instance, most of adverse reaction experienced from using Ibrance is reduction in neutrocyte, whereas Verzenio causes relatively insignificant changes in the neutrocyte level, but more prevalent adverse reactions in stomach are found.

 

But, the patients directly feel the stomach related adverse reactions, when the reduction in neutrocyte level is almost unnoticeable for patients unless they have fever or a drop in immunity level.

 

-It sounds like the preference on Ibrance would be up to patients’ situation It is so.

 

An elderly patient over 70 would highly prefer Ibrance.

 

Even patients in their 60s could prefer Ibrance, if they have underlying diseases like diabetes and hypertension, or not feel the best condition.

 

-But the experts say the downside of Ibrance is no available data on overall survival (OS).

 

Generally, an anticancer treatment clinical trial produces statistics based on a primary endpoint, and prioritizes in improving the Progression Free Survival (PFS) within the smallest group of patients.

 

As a first CDK4/6 inhibitor, Ibrance’ statistics had to focus on PFS than any other endpoint.

 

The first-in-class drugs tend to go through generically conventional design of clinical study.

 

Kisqali’s study was designed to analyze OS and PFS by setting the OS as the key secondary endpoint.

 

A latecomer can learn from the first-in-class drug and take a bolder step in a clinical study.

 

Personally, the most integral factor would be the hazard ratio in PFS.

 

All three of the drugs showed similar level of hazard ratio ranging from 0.5 to 0.6.

 

When CDK4/6 inhibitors’ real world data accumulate in the future, more clear answer would be given.

 

-The recent trend in the indication expansion among anticancer treatments seems to highlight adjuvant therapy after the release to diversify the indication.

 

Do you think the adjuvant therapy is crucial in CDK4/6 inhibitors?

 

To be honest, I am skeptical about the need of patients in stage 2 or earlier taking CDK4/6 inhibitor, while enduring the adverse reaction.

 

As 40 percent to 50 percent of stage 3 patients would relapse, administering CDK4/6 inhibitor for two to three years would make sense when the OS benefit is significant.

 

But, there is also concern about which medication to use when the cancer cells metastasize after using CDK4/6 inhibitor in adjuvant therapy.