Will Tagrisso finally be reimbursed with public support?

attempts reimb again...fueled by public petition

Attention focused on the CDDC meeting that will be held in March... 3rd time the agenda is being deliberated

Over 50,000 people show support...National Assembly also supports reimb

The D-day has finally been revealed.

 

Will the lung cancer treatment ‘Tagrisso’ finally succeed in extending reimbursement to the first line?

 

According to industry sources, AstraZeneca’s EGFR mutation-positive non-small cell lung cancer (NSCLC) treatment Tagrisso will be deliberated at the Health Insurance Review and Assessment Service’s Cancer Disease Deliberation Committee meeting on March 22.

 

A dire need had long existed.

 

The public petition urging for the extension of reimbursement benefits to the first line for Tagrisso that had been filed earlier this year had received consent from 50,000 people.

 

Patients desperately want it, but doctors are saying no to it.

 

Under such strange circumstances, Rep.

 

Jung-Sook Suh of the People Power Party had pointed to the need to extend reimbursement, upon which the Ministry of Health and Welfare expressed intent on its review.

 

The pharmaceutical company had also expressed its strong will to extend Tagrisso’s reimbursement to the first line, by accepting the financial-sharing plan proposed by the authorities.

 

Four years have already passed.

 

Tagrisso, which added its first-line indication in December 2018 in Korea, attempted to extend its reimbursement to the indication in 2019.

 

However, upon review by the Cancer Disease Deliberation Committee in October, the committee decided to defer the decision until the full data from the Phase 3 FLAURA trial that studied the overall survival (OS) of Tagrisso in NSCLC patients in the first-line was disclosed.

 

Although AstraZeneca submitted the full FLAURA data and expressed their will to accept most of the financial-sharing plan proposed by the government, the reimbursement fell through due to opposition from committee members (specialists) that raised an issue over the drug’s clinical efficacy.

 

At the time, the largest obstacle that impeded Tagrisso’s reimbursement in the first line was the Asian subgroup analysis results of the FLAURA trial.

 

Tagrisso’s overall survival (OS) in the trial was 38.6 months, a significant extension of 6.8 months over its first-generation comparators ‘Iressa (gefitiniib)’ and ‘Tarceva (erlotinib)’.

 

The results were encouraging, considering how Tagrisso was the first EGFR TKI to demonstrate efficacy in the first line and that crossover prescriptions were allowed for research ethics in patients with confirmed T790 mutations while receiving treatment with its first-generation comparators.

 

However, the issue was the hazard ratio (HR) of the Asian subgroup analysis.

 

HR was 0.995 when separately analyzing Asian patients that received Tagrisso.

 

An HR of 0.995 means that the difference between Tagrisso and the control group is 0.005, which could be interpreted as that there is virtually no difference between Tagrisso and its comparator.

 

This was why the academic society raised the opinion that ‘Tagrisso’s OS in Asians, including Koreans, was not reliable in the first line,’ and the opinion had a dominant influence on the results of the CDDC review.

 

Many others have expressed different views on the subgroup analysis results.

 

A primary efficacy endpoint exists for all trials, and subgroup analysis results are only presented as a reference only when the trials satisfy the primary efficacy endpoint.

 

This is the universally accepted concept in virtually all academia beyond medicine.

 

However, the expert committee pointed to the subgroup analysis as the key reason for the non-reimbursement even though the trial succeeded in demonstrating the OS, which was the purpose of the trial.

 

Regardless of what happened in the past, the agenda is again awaiting CDDC review.

 

Tagrisso has reinforced support with drug price cuts and real-world data that was announced last year.

 

In other words, the company has strengthened grounds for support from the financial and effect aspect.

 

Therefore, the industry’s attention is on whether Tagrisso will be able to produce a different result this time.

 

Meanwhile, the real-world study evaluated the effect of Tagrisso in the first-line in clinical practice in 660 NSCLC patients with EGFR mutations from 2018 to 2020.

 

583 of the patients received Tagrisso in the first line, and the other 76 received another EGFR-targeted cancer therapy.

 

Actual measurement was taken every 6 months in the 583 patients that received Tagrisso.

 

The median follow-up period was 24.6 months.

 

Results of the study showed that the median progression-free survival (mPFS) in patients that were administered Tagrisso was 20.0 months.

 

This is even longer than the mPFS of 18.9 months that had been identified in the global Phase III trial of Tagrisso.

 

By mutation, Tagrisso’s mPFS in patients with exon19 deletions was 23.5 months.

 

In those with L858R mutations, the PFS was 17.0 months.

 

In terms of OS, the median OS was 33.1 months in the Tagrisso arm, 7.4 months longer than the 25.7 months in the control group, reaffirming Tagrisso’s overall survival of over 3 years.