Immunotherapy shows effect as first-line treatment for BTC

[ESMO Asia 2022] Do-Youn Oh, Professor of Oncology at Seoul National University Hospital

Persuaded pharmaceutical company after discovering the potential for immunotherapy in biliary tract cancer and studied Imfinzi

Investigator-led trial leads to FDA approval...Imfinzi becomes the standard first-line treatment in biliary tract cancer... brings new hope to patients

Biliary tract cancer has long remained an area in which no new drug has been developed.

 

Following targeted therapies, immunotherapies have led to remarkable advances in anticancer treatment, but biliary tract cancer has been neglected in terms of developing new drugs.

 

This is because it has a lower prevalence rate than other cancers like lung cancer or stomach cancer, and even lower incidence in the West, which has been leading the development of new drugs.

 

In this area with minimal progress, AstraZeneca’s cancer immunotherapy Imfinzi obtained indication in Korea and abroad as a first-line treatment in biliary tract cancer.

 

In Korea and abroad, Imfinzi became the first immunotherapy to be approved as a first-line treatment in biliary tract cancer, and this latecomer among immunotherapies beating its competitors like Keytruda and Opdivo and won the “first” title.

 

One thing to note is that a Korean medical team led to Imfinzi’s global approval in biliary tract cancer.

 

Professor Do-Youn Oh’s persuasion was what moved the pharmaceutical company to pursue this unattended area.

 

At the European Society of Medical Oncology (ESMO) Asia Congress 2022 that had been held on the 2nd (local time) in Singapore, Professor Oh said, “I believe the biggest achievement that has been made is that Imfinzi’s first approval as a first-line treatment in biliary tract cancer opened the stage for other immunotherapies to take on research into the field of biliary tract cancer.”

Professor Do-Youn Oh

Around 10 years ago, Professor Oh proposed an investigator-led trial to pharmaceutical companies that own cancer immunotherapies after finding out that immunotherapies show relatively higher effects in biliary tract cancer.

 

However, companies at the time were more focused on cancers that have many patients and showed little interest and a low understanding of biliary tract cancer itself.

 

Oh recalled, “I proposed a clinical trial on biliary tract cancer to all companies that own cancer immunotherapies at the time.

 

I offered to test the drug myself to AstraZeneca’s clinical team.

 

The company accepted my offer, and so began the investigator-led Phase II clinical trial.

 

The trial went well thanks to the AstraZeneca team's active engagement.

 

Professor Oh and AstraZeneca designed a detailed and thorough clinical trial after long discussions.

 

They added 2 cohorts and enrolled more subjects.

 

Based on the anti-tumor effect and safety confirmed in Oh’s trial, a global Phase III trial was initiated, and Professor Oh took the role of principle investigator (PI) in the Phase III TOPAZ-1 trial.

 

The TOPAZ-1 trial was a success.

 

The Imfinzi arm (Imfinzi+ gemcitabine + cisplatin) showed a 20% improvement in overall survival (OS) versus the placebo arm (placebo+ gemcitabine + cisplatin).

 

Further analysis showed a higher OS improvement of 24% in the Imfinzi arm.

 

At 2 years, the 2-year survival rate in the Imfinzi arm was 23.6% compared with 11.5% in the placebo arm.

 

Median PFS (mPFS) was 7.2 months for the Imfinzi arm, a 25% improvement over the 5.7 months shown in the placebo arm.

 

Also, the Imfinzi arm achieved an objective response rate (ORR) of 26.7% (91 cases), 2.1% (7 cases) of which showed complete response, and 24.6% (84 cases) showed partial response.

 

Based on Oh’s investigator-led trial and TOPAZ-1 results, the US FDA approved Imfinzi for the treatment of biliary tract cancer.

 

Furthermore, the National Comprehensive Cancer Network recommended Imfinzi as the standard (Category 1) first-line treatment in biliary tract cancer.

 

For the first time, a cancer immunotherapy drug was listed as a standard of care in a field that only had chemotherapy options.

 

This was a very unusual case where a clinical trial initiated by a Korean healthcare professional led to global approval and a standard-of-care designation.

 

Professor Do-Youn Oh is presenting her findings at the ESMO Asia Congress 2022

Even after the approval, Professor Oh is busy conducting further analysis on TOPAZ-1.

 

At the ESMO Asia Congress, Oh presented results on the impact of mutation status on efficacy outcomes in the TOPAZ-1 trial.

 

The result of the study, which was the first to analyze the effect of cancer immunotherapies according to mutation status, was that there was no significant difference in the effect of cancer immunotherapies depending on the presence or absence of major mutations.

 

Professor Oh referred to the entry of Imfinzi in biliary tract cancer as a ‘starting point’ that opens the stage and drives the development of biliary tract cancer treatments.

 

In other words, an area that has not been tried due to lack of knowledge and lack of interest has opened up for research.

 

Oh said, “With the TOPAZ-1 study, people have come to recognize that immunotherapies can be developed for biliary tract cancer as well.

 

With so many cancer immunotherapies of various mechanisms of action in development, the biggest significance held by the success of the TOPAZ-1 trial is that the stage has been set for these to be tested in biliary cancer as well.” Above all, Oh expressed pleasure in providing new hope for biliary tract cancer patients.

 

Professor Oh said, “Polarization of treatment options exists in the field of cancer as well.

 

Some cancers offer many treatment options, others less than few.

 

Biliary tract cancer was one of those that had almost no available treatment options.

 

Whenever my patients asked why they can’t use immunotherapies, all I could do was tell them that a research was underway.

 

With an immunotherapy option now available for biliary tract cancer, I look forward to more progress being made in the field and various more studies to come.”