the era of Lung cancer cure

Benefits should also consider the meaning of adjuvant therapy

[Interview] Han Ji-yeon, Professor of Hematology and Oncology, National Cancer Center

Tagrisso improves overall survival following progression-free survival

The third-generation EGFR-targeting anti-cancer drug Tagrisso (Osimertinib) has left a unique record in non-small cell lung cancer.

 

Significant improvement was achieved in adjuvant therapy after surgery, and it was also proven that survival time could be extended.

 

This is an area that previous TKI drugs have failed to overcome.

 

Tagrisso has already demonstrated that it can reduce the risk of recurrence or death by about 80% through the phase 3 clinical trial of ADUARA three years ago.

 

Since then, people's attention has been focused on overall survival.

 

I wondered how much longer actual patients could live if Tagrisso was used early.

 

The results were revealed at ASCO 2023 held this year.

 

As a result of analyzing the overall survival rate at 5 years, the risk of death in the Tagrisso group was 88%, compared to the placebo group (78%), and the risk of death was reduced by 51% (HR=0.49).

 

The overall survival improvement of Tagrisso was consistently shown in the sub-analysis according to sex, age, race, smoking history, and adjuvant chemotherapy.

 

Professor Han Ji-yeon, National Cancer Center.\

Han Ji-yeon, professor of hemato-oncology at the National Cancer Center, said, "Following the primary evaluation variable, DFS, OS improvement also showed data of HR of 0.49." It was groundbreaking in that it opened." The reason for administering adjuvant chemotherapy after surgery in early patients is to minimize the possibility of recurrence by preventing very small tumors from remaining in the early stage.

 

However, the cytotoxic anticancer drugs used before Tagrisso were not very effective in reducing recurrence.

 

According to Professor Han, cytotoxic anticancer drugs do not respond well to patients with EGFR-mutated lung cancer, so more than half suffer recurrence.

 

With the introduction of Tagrisso, the recurrence rate of patients dropped significantly from 3% in the first year to 10% in the second year.

 

At 3 years, 78% of patients still had no recurrence of cancer.

 

Tagrisso ADAURA OS graph (source ASCO)

According to the sub-analysis, the risk ratio was slightly higher in the L858R patient group than in the exon 19 deletion patient group among EGFR mutation types, at 0.68, but still proved the benefit of Tagrisso.

 

Regarding this, Professor Han explained, "The receptor mutation structures of the exon 19 defect and L858R are different, but compared to the L858R mutation, the exon 19 defect has a structural feature that TKI adheres well." Professor Han explained, "Also, the L858R mutation rate was relatively higher in Asians, so the results were better in non-Asians.

 

There is no way to solve the difference due to the characteristics of genetic mutations biologically." Following the DFS risk ratio of 0.17, the primary endpoint, the OS risk ratio of 0.49 was added, and Professor Han emphasized that Tagrisso's position in postoperative adjuvant therapy has become more solid.

 

In addition, he emphasized the need to change the perception of reimbursement registration for adjuvant therapy.

 

Earlier, in a discussion session on adjuvant treatment after Tagrisso surgery at ASCO, she said, "10% of patients who would not have survived 5 years without Tagrisso are alive." Then, an opinion was raised that “global support is needed to provide support for early screening and treatment so that the gap and inequality in global access to effective cancer treatment does not deepen.” In Korea, Tagrisso can still be used as a reimbursement only for the second or higher treatment only for progressive and metastatic cases, leaving a large gap with the global market.

 

Professor Han said, “It has been about five years since Tagrisso was approved in Korea, but it is not yet covered by insurance as a first-line treatment.

 

Considering the global trend, discussing first-line treatment benefits is too late.” If it goes well, I think that Tagrisso should be provided even in the environment of early lung cancer adjuvant therapy, which opened the 'era of lung cancer cure'," she emphasized.