The efficient use of CDK 4/6 needs to be discussed

for early breast cancer progression

[ASCO 2023] Expansion of CDK 4/6 inhibitor treatment area

Primary indicator risk ratio 0.74

Pay attention to the effects of a wide range of patients and lower doses

Dr.

 

Dennis J.

 

Slamon presented the clinical results of NATALEE at ASCO 2023 held in Chicago on the 2nd (local time)

CDK4/6 inhibitors, which were prevalent in metastatic breast cancer, have expanded their scope to early breast cancer.

 

Following Lily Verzenio, Novartis Kisqali demonstrated the effect of adjuvant therapy after surgery through a clinical presentation this year.

 

As the role of CDK4/6 inhibitors expands, new concerns are emerging to achieve the best cost-effectiveness.

 

Joo-Hyeok Son, a professor of oncology at Yonsei Cancer Hospital, who met at the 'American Society of Clinical Oncology Annual Conference (ASCO 2023)' held for five days from the 2nd (local time) said, "The risk ratio (HR) of Verzenio is slightly higher than the risk ratio (HR) shown in early breast cancer.

 

However, as time goes on, it remains to be seen whether the Kisqali group will be able to widen the difference between the control group and the control group,” he said.

 

Although they are the same class of drugs, the clinical designs of the two drugs in early breast cancer are different in many ways.

 

First of all, Verzenio was targeted for administration to high-risk patients with lymph node metastases.

 

Kisqali did not limit the presence of lymph node metastasis.

 

A relatively low-risk patient group was also included in the clinical trial.

 

The dose and duration of administration are also different.

 

Verzenio uses the same dose as for metastatic breast cancer, and after two years of administration, only endocrine therapy is continued.

 

On the other hand, Kisqali lowered the dose by two-thirds and set the duration of administration to 3 years while conducting clinical trials.

 

It appears to be intended to lower the risk of side effects by reducing the dose.

 

Attention is focused on whether such differences in clinical design will affect the data.

 

Professor Sohn said, "The risk ratio of the primary indicator shown by Kisqali at this conference was 0.74, which did not reach the initial result of Verzenio.

 

The risk ratio was similar in advanced breast cancer, but slightly different results in early breast cancer." Several factors, such as condition and dose, may have had an impact." Prof.

 

Sohn thinks that Verzenio, which has released four-year follow-up data, is in a slightly more solid position in early breast cancer.

 

However, there is room for Kisqali to show more improved data over time.

 

In fact, Verzenio showed a sustained effect even after the two-year administration period was over.

 

The invasive disease-free survival (iDFS) rate of Verzenio, which showed a difference of 2.8%p from the control group at the 2-year follow-up, widened to 6.4%p at the 4-year follow-up.

 

At 4 years, the hazard ratio was 0.66, and the improvement effect was greater than that of 0.70 a year ago.

 

As the treatment area for CDK4/6 inhibitors expands to early breast cancer, new concerns are emerging.

 

Representatively, the problem is how to set the patient group that can see the most CDK4/6 inhibitor effect.

 

Some point out that CDK4/6 inhibitors improve iDFS by 2-3 percentage points over control.

 

This means that out of 100 patients treated, only 3 patients will benefit from improvement.

 

In fact, after the NATALEE study results were announced at ASCO, during the discussion session, "It is questionable whether the medical system can afford the cost of improving 3 out of 100 people in a situation where pharmaceutical costs alone cost 15 million dollars." told In this discussion session, another question was asked, "Is it possible to establish a group of patients who are more likely to receive the CDK4/6 inhibitor effect?" Professor Sohn also explained, “A consensus is needed on whether to prevent the recurrence of the three patients by spending about 65 billion won in a situation where the drug must be used for 2 to 3 years.” Professor Sohn predicted, "In the end, we have to find a biomarker (which can measure the effect of CDK 4/6 inhibitors), but it will not be an easy process."