"Embrace precision medicine and tumor-agnostic therapy"

[Interview] Kyong-Hwa Park, Professor of Oncology and Hematology at Korea University Anam Hospital

“Succeeded in initiating 20 clinical trials for ‘Lazertinib’ etc. through the K-Master project ”

A separate track needs to be prepared by regulatory authorities for personalized medicines like Rozlytrek etc.

박경화 교수

“It’s our turn to adjust to tumor-agnostic therapies." HER2, ALK, EGFR, ROS1.

 

These are keywords that frequently catch our eye in news about anticancer drugs.

 

Times have changed.

 

Effective treatment for patients these days depends on the genetic mutation of each patient.

 

With treatments that target personalized genes continue being introduced, the development of precision medicine has heralded the shift in the field of anticancer treatment from ‘disease-based' to ‘gene-based' treatment.

 

For example, Roche’s Neurotrophic tyrosine receptor kinase (NTRK) ‘Rozlytrek (entrectinib)’ has already been approved as a tumor-agnostic anticancer drug in Korea.

 

Also, MSD’s PD-1 inhibitor immunotherapy ‘Keytruda (pembrolizumab)’ has been adding various indications in patients with microsatellite instability-high (MSI-H) tumors.

 

Dailypharm met with Dr.

 

Kyong-Hwa Park, Professor of Oncology and Hematology at Korea University Anam Hospital, an authority in the field of precision medicine in Korea who also runs the K-Master program, to hear about the currently accessible yet unfamiliar world of personalized treatment, and the paradigm shifts that have occurred in anticancer treatment with the introduction of precision medicine.

 

-Precision medicine has become an inevitable trend.

 

Please tell us about the K-Master project, its progress, and outcome.. Initially, our 5-year goal was to file genome sequencing of 10,000 patients with solid cancer and to launch 20 clinical trials.

 

Based on the data, we wanted to provide new treatment opportunities to patients and create grounds to expand treatment indications.

 

We are in our fifth year, and our project will close on December 31st this year.

 

Since we already have registered and secured genome sequencing data on 9,000 cases, I think we will be able to easily reach our goal.

 

We are also currently conducting 20 trials.

 

Due to the characteristics of precision medicine, the 20 clinical trials could not be initiated all at once, so we needed to sequentially proceed on with our research.

 

In other research areas, we could have started all the trials in the first year.

 

However, precision medicine differs from other areas because of its unmet needs, as well as its unique timeline of drug development that depends on the discovery of new genes.

 

-What is the K-Master program’s strength in conducting clinical trials? Our role model was the NCI (National Cancer Institute)-Match trial.

 

Based on the trial and its limitations, we complemented and improved our project from its initial stages.

 

When 50 institutions under the Korean Cancer Study Group send sample tissues, Central conducts NGS sequencing; however, if the sample tissues do not pass QC, the process of recollecting the tissues take long, and in some cases result in the non-registration of those patients.

 

For our project, we increased the registration success rate by profiling the samples via a liquid biopsy platform to allow the use of blood samples for genome sequencing of patients whose tissues are unavailable or do not pass QC.

 

- Two drugs, including Rozlytrek, were approved in Korea.

 

These tumor-agnostics targeted therapies seem like typical examples of how ‘personalized medicine’ and ‘precision medicine’ are entering our society.

 

What changes do you expect to see in Korea with the introduction of such medicines? The method of how we classify cancer has changed with the introduction of precision medicine.

 

If cancer was classified by location in the past, like lung cancer, colorectal cancer, breast cancer, etc., now it is divided by pathway.

 

So we can now classify cancer as those with HER2 overexpression, HER2 mutation, NTRK mutation, etc.

 

Patients with such cancers are very rare, but doctors now know what to prescribe when such cases arise because we have research and findings on such cases.

 

We can therefore use various methods to find the NTRK-mutations such as DNA sequencing, RNA sequencing, at the protein level or by FISH, etc.

 

As DNA NGS has low sensitivity, we would be lucky to find the mutation at that level.

 

However, for suspected patients, doctors can also order FISH or IHC tests.

 

-Reimbursement remains an obvious issue.

 

Reimbursing tumor-agnostic treatments must be a burden from the government’s perspective. When treatment for rare cancer types that occur in specific genes are granted evidence-based approval in the market, reimbursement should also be considered.

 

I believe the higher-priced drugs can be reimbursed as rare cancer patients have a shorter life expectancy.

 

Less than 1% of all solid cancer patients in Korea fall into the rare cancer patient category that can benefit from such advanced treatments.

 

Considering our diagnostic efficiency, this amounts up to less than 200 patients.

 

We are talking about providing treatment benefits to these very rare patients.

 

If reimbursement is possible, it should be provided.

 

Rare cancer patients typically do not respond to standard treatments.

 

For example, breast cancer patients that do not respond to standard of care therapies show NTRK mutations.

 

As these patients benefit a very short time from standard treatment, reimbursement of NTRK inhibitors for this population should also be possible.

 

Overall, we need to devise a separate reimbursement track for precision medicine.

 

With the introduction of Keytruda in MSI-H and Rozlytrek, there is a pressing need to prepare a separate reimbursement review standard for tumor-agnostic treatments that suits our current situation.

 

If precision medicine is available according to a patients' NGS screening result, they should not be left to feel the immense deprivation of not being able to use the drug due to accessibility issues.