“Tagrisso shows effect as 1st-line in the real world"

[ESMO Asia 2022] Frank Griesinger, Professor of Hemato-Oncology from Germany

Presents large-scale real-world study results from Germany and Japan

Enrolled high rate of patients with poor prognosis such as brain metastasis or rare mutations... shows consistent effect

“No reason not to use Tagrisso in the first line...demonstrated effect in Asians as well”

AstraZeneca’s 3rd generation EGFR mutation-positive non-small cell lung cancer (NSCLC) treatment ‘Tagrisso (osimertinib)’ has shown consistent effects with the clinical trial results in practice.

 

In the real world, Tagrisso demonstrated excellent treatment effects even in patients with brain metastasis, poor systemic condition, or patients with rare mutations.

 

The real-world study results from Germany and Japan that contained the results above were presented at the ESMO Asia 2022 Congress that has been held in Singapore on the 2nd.

 

The large-scale, real-world studies evaluated the use of Tagrisso as a first-line treatment in the field on 600 patients in Japan and 200 patients in Germany.

 

Japan large-scale real-world study results (Source: ESMO)

In the Japanese trial that analyzed 583 patients, Tagrisso achieved a median progression-free survival (mPFS) of 20.0 months and median overall survival (mOS) of 4.09 months.

 

By mutation, Tagrisso’s PFS in patients with exon19 deletions reached 23.5 months.

 

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

 

In terms of OS, the OS was 36.1 months in the L858R mutation group, and the median OS was not reached in the exon19 deletion group.

 

German large-scale real-world study results (Source: ESMO)

In the German trial that analyzed 217 patients, the time to next treatment or death (TTNTD) and the time to discontinuation (TTD) were measured.

 

Results showed that Tagrisso’s mPFS was 16.2 months, TTNTD 19.2 months, and TTD 14.8 months.

 

In other words, Tagrisso demonstrated an excellent effect not only in patients with brain metastasis that are commonly found in NSCLC but also in patients with rare EGFR mutations.

 

Especially, the rate of patients with brain metastasis accounted for 38% of all patients enrolled in the German real-world study, and 11% were patients with rare mutations that had been excluded from clinical trials.

 

Also, 14% were patients with poor prognosis, the ECOG PS2-3 NSCLC patients.

 

During an interview with Dailyphram, Professor Frank Griesinger of Hemato-Oncology from Germany at Pius-Hospital Medical Campus, University of Oldenburg, said, “Unlike how tests are conducted every 6-8 weeks to evaluate PFS in clinical trials, the PFS in real-world studies tends to be shorter due to longer testing intervals in the field.

 

Tagrisso showed a consistent effect in the real-world study despite the fact that the study enrolled a higher proportion of patients with brain metastasis and rare mutations or poor general conditions, and their age was around 4 years older.

 

Professor Frank Griesinger

Professor Griesinger added that over 90% of EGFRm NSCLC patients in Germany choose to use Tagrisso in the first line.

 

He explained that sequential therapy with Tagrisso where other 1st or 2nd-generation treatments are first used followed by 3rd generation drugs may deprive patients of their opportunity to use Tagrisso.

 

Professor Griesinger said, “If you look at the treatment journey of those that undergo sequential treatment, only 70 to 80% of those with advanced disease can receive mutation testing as patients who have already developed resistance often do not have enough tissue left to perform a biopsy.

 

Blood biopsy is somewhat less accurate.

 

Besides, only 38% of Asians are found to receive biomarker testing after developing resistance.

 

Considering how only around half of the few that are tested are T790M-positive, not many patients can use Tagrisso as later line therapies.” He added, “One mistake most people make in the course of making treatment decisions is that the OS data of Tagrisso is good as sequential therapy.

 

But the results have to be better as the data comes from the selected 30% of patients who are eligible to use Tagrisso in the first place.

 

We should not overlook the other 70% of the patients that cannot use Tagrisso in that environment” The OS from the Asian subgroup analysis results for Tagrisso’s Phase III trial has raised controversy.

 

Although Tagrisso showed statistically significant improvement in the entire patient group, the risk ratio (HR) was 0.995 when separately analyzing the Asian patients in the population.

 

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

 

Regarding Tagrisso’s effect on Asians, Professor Griesinger said “Some parts of the Asian sub-analysis results have been difficult to interpret, but I don't think it's is an issue because the total OS shown demonstrates improvement in the entire population.

 

Tagrisso effect was also consistent in the Japanese real-world study.” Professor Griesinger emphasized, “Based on my practice and research experience Tagrisso is a worthy first-line standard therapy.

 

If the patient has EGFR mutation, there is no reason not to use Tagrisso.”