“I strongly recommend Retevmo as first-line treatment”

Professor Kaname Nosaki, National Cancer Center Japan

First RET inhibitor...occurs in 2-6% of NSCLC patients

Response rate 85% when used in the first-line, median DoR 18.4 months

“Using immunotherapies first reduces response rate and raises toxicity concerns...use of targeted therapies should be considered first”

Reimbursement listing for Lilly’s ‘Retevmo(selpercatinib),’ which opened a new door to treating RET-targeted mutations, is gaining momentum in Korea.

 

If approved for reimbursement, the scope of treatment for patients with RET mutations is expected to broaden significantly.

 

In November this year, the Cancer Disease Deliberation Committee of the Health Insurance Review and Assessment Service set the reimbursement standards for Retevmo in non-small cell lung cancer (NSCLC) and thyroid cancer and is up for deliberation by the Drug Reimbursement Evaluation Committee (DREC).

 

As HIRA announced it will reduce the reimbursement listing period by 30 days for drugs that treat life-threatening diseases like Retevmo, discussion on the drug’s reimbursement is expected to speed up further.

 

Retevmo is the first targeted therapy that targets the RET mutation.

 

The RET gene is in charge of the formation of normal organs as well as the maintenance of various tissues including neural, neuroendocrine, hematopoietic, and male reproductive cells.

 

However, the abnormal activation of RET due to mutations in the RET gene, such as fusion or point mutation causes malignant tumors.

 

The mutation is mostly found in NSCLC, thyroid cancer, and medullary thyroid cancer.

 

In NSCLC, RET mutation occurs in 2 to 6 % of all cases.

 

The drug is already being used actively in the field in Japan, where Retevmo was approved earlier and is being reimbursed.

 

Dailypharm interviewed Professor Kaname Nosaki of the National Cancer Center Japan (Department of Thoracic Oncology) to seek insight into Japan’s treatment experience with Retevmo in RET fusion-positive NSCLC.

 

Professor Kaname Nosaki, National Cancer Center Japan

In the interview, Professor Nosaki stressed the need for Retevmo in patients with RET fusion-positive NSCLC.

 

Prior to its introduction, patients had no other option but to use chemotherapy, which has high toxicity.

 

Professor Nosaki said, “With no other targeted therapy available before Retevmo, patients who were identified with RET mutations had no other option but to receive chemotherapy.

 

As expected, due to poor treatment prognosis and low rate of survival, a strong unmet need existed in the field.

 

Retevmo is very necessary for these patients as it has demonstrated excellent clinical efficacy, duration in effect, and excellent safety.” The Japan Lung Cancer Society updated its clinical practice guidelines to strongly recommend the use of Retevmo in patients with RET fusion-positive NSCLC who have no prior treatment experience.

 

The recommendation is based on the LIBRETTO-001 trial that was conducted on 702 patients with advanced or metastatic solid cancer with RET mutations.

 

The objective response rate (ORR) of Retevmo was 85% in patients with no prior chemotherapy experience.

 

Also, 79% of the Retevmo patients showed continued response during the follow-up period (median 7.4 months).

 

The ORR was slightly lower in patients with previous treatment experience but was still 64%.

 

The median duration of response (DoR) was 17.5 months.

 

Professor Nosaki said, “The overall survival (OS) is yet to be reached in the Retevmo trial.

 

We need to continue monitoring the data, but we are positive about the results as the 2-year survival rate of enrolled patients is near 70%.

 

When the OS has not been reached, we evaluate results based on progression-free survival (PFS) or duration of response (DoR), and Retevmo showed good results in the criteria with an mPFS of 18.4 months and DoR of 20.4 months.

 

He emphasized that the use of Retevmo in the first line should be considered after identifying RET mutations in the initial stages of diagnosis in patients with NSCLC.

 

Due to differences in the diagnostic environment, the less common RET mutations are identified relatively later than other mutations.

 

In other words, patients are first searched for major mutations such as EGFR·ALK·ROS1, and those without these mutations are prescribed cancer immunotherapies and then identified for minor mutations.

 

Therefore, patients found with RET mutations at this time may only use Retevmo in the second line.

 

On this, Professor Nosaki said, “Patients with a certain mutation may not respond well to immunotherapies, therefore, treatment sequence is all the more important in these patients.

 

Unexpected toxicity problems may occur when using cancer immunotherapies first then using TKIs, which may lead to pneumonia or liver function deterioration.” He added, “Therefore, if available, it is more appropriate to use the targeted therapy first.

 

Doctors should quickly identify major and minor mutations with next-generation sequencing (NGS) from the early stage of diagnosis to allow patients to be treated with good drugs early on."