Leclaza confirms brain metastasis benefits

Yonsei Cancer Hospital Department of Oncology Professor Hyeryun Kim and Professor Minhee Hong Presented at ASCO

"It is meaningful as it is the first study focusing on two ORRs"

"I think this is a meaningful study in that the third-generation EGFR TKI treatment, such as Lazertinib, showed data related to brain metastasis, but clearly focused on the intracranial response to confirm the effect." When brain metastasis occurs in non-small cell lung cancer patients using 1st or 2nd generation EGFR TKI agents, most patients' condition deteriorates rapidly, and furthermore, in the case of T790M negative, options are limited.

 

A new therapeutic basis has emerged.

 

A domestic phase 2 study that confirmed the effect of Lazertinib, the third generation, on patients with brain metastasis after failure of the existing 1st or 2nd generation EGFR TKI drugs in EGFR mutated non-small cell lung cancer was presented as a poster at the American Society of Clinical Oncology Annual Meeting (ASCO) this year.

 

Professor Hye-ryeon Kim and Professor Min-hee Hong of Sinchon Severance Hospital Cancer Hospital, who led the study, said in an interview with the Medical Times, "It is meaningful in terms of IIT related to Lazertinib." It will be helpful in terms of future patient care.” In this study, 40 EGFR-positive patients who showed brain metastases after using first- and second-generation treatments were enrolled.

 

The primary objective is to evaluate the intracranial activity effect of Lexraza in patients with asymptomatic or mild brain metastases.

 

Professor Kim said, "When treating lung cancer patients with EGFR mutations, there are many experiences of brain metastasis, patients with poor prognosis, and rapidly deteriorating." It is very important to control the progression of brain metastases in EGFR-positive patients in a situation where they cannot survive long despite treatment such as back,” he explained.

 

"In this respect, it is important to have a treatment that passes the Blood-Brain Barrier or BBB well, and Leclaza has good permeability to brain metastasis in preclinical studies, so we decided to evaluate it in clinical trials," he said.

 

In the actual study, patients who failed the existing treatment were divided according to the presence or absence of the T790M mutation.

 

The primary evaluation index was the intracranial objective response rate (iORR), and the secondary evaluation index was the intracranial iPFS.

 

Regarding this, Professor Hong explained, "In clinical trials of Osimertinib, ORR was confirmed, and the brain was separately analyzed in relation to CNS metastasis in it." Professor Hong emphasized, “It is meaningful in that it is the first time that the objective response rate within the two was confirmed as the primary evaluation index.” In particular, the fact that the number of T790M-negative patients in this study was 33 compared to the T790M-positive five patients is also an eye-catching factor.

 

In fact, Lazertinib and Osimertinib can be reimbursed in the case of T790M-positive patients, but in the case of T790M-negative patients, treatment options that can be used for patients are limited.

 

It is the view of the two professors that they have it.

 

Professor Hong said, “When metastasis occurs in the CNS, existing treatments have poor cerebral vascular penetration due to pharmacological mechanisms, so brain metastasis proceeds.

 

In this case, secondary mutations of the tumor itself do not occur easily.” It was concluded that therapies focused on the CNS were able to prevent the progression of brain metastasis to some extent.” The results of the study showed that the intracranial ORR of 38 evaluable patients was 55.3%, with 3 complete responses and 18 partial responses.

 

There were only 5 T790M-positive patients, but 4 showed a partial response, recording an intracranial response rate of 80%.

 

Of the 33 T790M-negative patients, 3 complete responses and 14 partial responses showed an objective response rate of 51.5%.

 

The overall PFS and the PFS period in the T790M positive and negative groups were analyzed to be 15.2 months, 9.9 months, and 15.4 months, respectively.

 

The duration of intracranial PFS was similar for T790M positive and negative at 15.2 months and 15.8 months, respectively.

 

Professor Hong said, “The design of the study itself is directly connected to the clinical field, and Lazertinib is helpful in patients with brain metastasis, and many of them did not have T790.” It is a study that shows the CNS response well while doing it.” It is evaluated that based on this study, options that can be considered in the clinical field can be increased.

 

The two professors also mentioned plans to increase permits based on the research results.

 

Professor Kim said, "The clinical trial was started and the recruitment of patients was faster than planned, which means that there is a lot of unmet demand." I would like to add significance in that this is a study that focused on iORR as the primary evaluation index and confirmed it, as the passing treatment is helpful." "Standard treatment is shifting from first-line treatment to third-generation treatment, but there are still many patients using first- and second-generation drugs," he said.

 

We plan to try to increase the permits,” he added.