CDK4/6 latecomer Kisqali exudes confidence in its effect

Seock-Ah Im, Professor of Hemato-Oncology at Seoul National University Hospital

The only drug to demonstrate an effect in aggressive breast cancer among CDK 4/6 inhibitors

Results hold significance in Korea for being allowed use in premenopausal patients

May replace highly toxic chemotherapy... use of CDK4/6is will continue to increase”

Novartis’s Kisqali (rivociclib), a latecomer CDK4/6 inhibitor used in metastatic breast cancer, is taking on an unexplored path, away from other CDK4/6 inhibitors.

 

The drug has demonstrated efficacy in aggressive forms of breast cancer, which had not been attempted by other CDK 4/6 inhibitors.

 

Aggressive breast cancers appear relatively often in Korea where the proportion of younger aged patients is large, but the patients’ only available option was to use highly toxic chemotherapy.

 

In a recent interview with Dailypharm, Seock-Ah Im, Professor of Hemato-Oncology at Seoul National University Hospital said, “Younger breast cancer patients have a higher probability of accompanying visceral metastasis because of their rapid cancer growth and aggressive clinical pattern.

 

However, due to the clinical practice guidelines that recommended using chemotherapy for the past 20 to 30 years, there were doubts about whether to use CDK4/6 inhibitors.

 

However, Kisqali's recent study convinced me of the viability of using CDK4/6 therapies." The recent study mentioned by Professor Im is the RIGHT Choice trial that was released in December last year.

 

The trial studied aggressive hormone receptor–positive, HER2-negative advanced breast cancer patients that had symptomatic visceral metastasis, rapid disease progression or impending visceral compromise, or marked symptomatic nonvisceral disease.

 

Although the CDK4/6 inhibitor+ endocrine therapy is currently used as the standard treatment for breast cancer in the first line, chemotherapy was still used in patients with rapid disease progression or visceral metastasis.

 

Metastatic breast cancer often spreads to the lungs, liver, or brain, and when metastasis occurs, symptoms such as shortness of breath and pain may arise.

 

In such cases, it is difficult to quickly reduce tumor size with hormone therapy alone.

 

CDK4/6 inhibitors have been introduced as a new option in this field, but no data existed demonstrating their effectiveness in these patients.

 

Kisqali is the only CDK4/6 inhibitor class drug to demonstrate an improved effect over combined chemotherapy in aggressive breast cancer.

 

Results showed that the median progression-free survival (PFS) of the Kisqali + endocrine therapy combination was 24.0 months, a 1-year extension over the 12.4 months recorded by the control group (HR=0.54).

 

The median time to treatment failure in the Kisqali combination group was 18.6 months, which was at least 10 months longer than that of the control group (HR=0.45).

 

In terms of safety as well, the Kisqali combination group had a lower rate of treatment-related serious adverse reactions and treatment discontinuation rate compared to the combination chemotherapy group.

 

Professor Lim said, "The scope of use of CDK4/6 inhibitors including Kisqali in HR+ breast cancer has increased significantly over the past two years.

 

In line with the broadened scope of use of CDK4/6 inhibitors that changed the treatment paradigm of HR+ breast cancer, the ground is being laid to allow their more active use.”

Professor Seock-Ah Im

-I heard that Asian doctors first suggested the initiation of the RIGHT Choice trial = I am a member of a group of researchers that seek to improve the treatment of young breast cancer patients.

 

As members, specialists from Asian countries, including Korea, Taiwan, Hong Kong, and Singapore, gather together to discuss and study how to improve the treatment environment for young breast cancer patients.

 

During a meeting, the researchers suggested that a combination therapy that uses a CDK4/6 inhibitor could improve the quality of life and have a better antitumor effect than combination chemotherapy, and a research proposal was sent to pharmaceutical companies based on the suggestion.

 

We proposed a study because young patients in their 40s and 50s occupy the majority population in Asia, compared to the West, which is dominated by elderly patients in their 60s and 70s.

 

Breast cancer often takes on an aggressive form among young patients due to the fast cancer growth rate and relatively faster cell division.

 

This means patients are highly likely to have accompanied liver or lung metastases.

 

These doctors had been using chemotherapy as the first-line treatment for HR+ patients because it takes a long time to improve the patient’s symptoms by reducing cancer size with hormone treatment.

 

Chemotherapy allows the tumor size to reduce within 1 to 2 months and the symptoms improve.

 

However, it is also highly toxic.

 

Therefore, a consensus was reached on how combining hormone therapy and targeted therapy instead of chemotherapy, which is difficult to be approved, would yield better results.

 

Novarits’s Kisqalit team accepted the request, and so the RIGHT Choice study was conducted to demonstrate the actual improvement effect..

 

-How would you interpret the RIGHT Choice trial results?

 

s= There had been clinical trials comparing hormone therapy and CDK4/6 inhibitors with oral anticancer drugs.

 

However, this study is the first to show improvement compared to a combination therapy that is administered in two injections of cytotoxic anticancer drugs.

 

In general, if a patient starts anticancer therapy, the tumor size is first reduced and then starts to grow again.

 

The time until disease progression, that is, the time to symptom relief after chemotherapy and relapse is about 5 to 6 months.

 

In clinical practice, the median time to treatment failure in the Kisqali combination group was 18.6 months, about twice as large as 8.5 months in the control group.

 

Median progression-free survival was also extended by about 1 year compared to the control group.

 

In particular, this study brings more significance because it includes premenopausal women and proves that a more comfortable initial treatment can be performed in premenopausal patients with more aggressive liver cancers or those with lung metastases.

 

The limitation is that the study enrolled patients whose control group could be either one of two cytotoxic anticancer drugs and have a normal range of liver function and daily performance ability to some extent.

 

The study did not include patients whose daily performance is so poor that they are almost bedridden.

 

There are some cases we feel it’s inappropriate to conduct chemotherapy in some patients with visceral metastasis.

 

However, on the other hand, there were many questions about whether it was really okay to use CDK4/6 inhibitor combination therapies.

 

The study convinced me of the potential held by 'CDK4/6 therapy.’ -Kisqality was the last of the three CDK4/6 inhibitors to be introduced to the market.

 

However, if you look at the recent sales records reported by the market research institution IQVIA, Kisqali made notable sales.

 

How reliable are new drugs like Kisqali?

 

=The data was interesting.

 

Having participated in the trial of all three CDK4/6 inhibitors, Ibrance, Verzenio, and Kisqali, I am well aware of the benefits and disadvantages of each drug.

 

Therefore, doctors tend to select drugs after comprehensively considering each patient’s safety, the patient's environment, and condition.

 

In the case of postmenopausal women, side effects such as age, presence or absence of pulmonary embolism or venous thrombosis, and probability of pneumonia are considered.

 

In addition, bone marrow function, liver function, electrocardiogram abnormality, and diarrhea are also considered.

 

However, re-menopausal breast cancer patients didn't have as many options to choose from.

 

Before Ibrance, the patient had to first remove both ovaries to use Ibrance.

 

Fortunately, the combination therapy with Ibrance after ovariectomy did not require chemotherapy, and had only a few side effects other than a slight decrease in white blood cell count, so this method was mainly used.

 

Later, the MONALEESA-7 study played a significant role.in allowing premenopausal women to use Kisqali combination therapy without ovarian resection.