In 2021, Korean biotech firm Bixink Therapeutics introduced Nerlynx Tab. (neratinib), a HER2 inhibiting breast cancer treatment developed by Puma Biotechnology and approved by the FDA in July 2017. The arrival of the drug drew much attention from the medical community.

In Korea, Nerlynx obtained approval in October 2021 as the nation’s first extended adjuvant therapy for patients with HER2-positive early breast cancer.

Korean patients are paying keen attention to what kind of benefits Nerlynx will offer.

Korea Biomedical Review sat down with professor Lee Kyung-hun of oncology at the Seoul National University Hospital to learn about the treatment environment for HER2-positive early breast cancer, the implication of Nerlynx’s arrival in Korea, and the necessity for reimbursement to raise patient access.

Lee explained that patients with lymph node metastasis or with a tumor in the breast larger than 2 cm often get chemotherapy before surgery. This is because it was the standard therapy for HER2-positive early breast cancer in many tertiary hospitals, including SNUH.

However, even after the standard care, some experience relapse and fail to reach complete remission (CR).

“HER2 tumors can relapse in many cases. So if there is no CR after taking neoadjuvant chemotherapy, which is currently widely used as the standard treatment, the risk of recurrence is quite high, and both the patient and the doctor will be worried,” Lee said.

Whether the patient achieved CR or not after neoadjuvant chemotherapy will decide a later-stage treatment. New HER2-targeting medicines are emerging for those with recurrent tumors or who could not reach CR, and Nerlynx is one of them.

“Nerlynx was authorized in Korea as an extended therapy for additional one-year treatment after completing Herceptin-based therapy as postoperative adjuvant therapy. The drug is the only extended treatment,” Lee said. “It was meaningful to introduce Nerlynx in Korea because the extended adjuvant therapy lowered the recurrence rate.”

Lee said that if a patient fails to reach CR after neoadjuvant therapy, she can use Kadcyla (trastuzumab emtansine), which became reimbursable in Korea. In this case, the CR rate goes up a little bit but not to 100 percent, he noted. In such a scenario, he said it is meaningful that the patient can still use Nerlynx.

So far, medicines targeting HER2 showed greater efficacy in patients whose tumors were hormone receptor-negative but were more dependent on HER2.

Nerlynx worked better if the patient was hormone-positive and HER2-positive, Lee said.

Still, Lee was cautious about Nerlynx’s effect on lowering the incidence of brain metastasis. He said that the drug surely reduced the incidence of brain metastasis, but it was difficult to compare its effect with those of conventional treatments directly.

According to Lee, HER2-positive early breast cancer can spread to other organs, and brain metastasis occurs frequently.

“Sometimes, patients have brain metastasis even after achieving CR through neoadjuvant therapy. These are very nasty cases,” he said. Some explain that brain metastases occur probably because drugs cannot enter the brain well, he added.

This issue can be controversial, but it is difficult to say that existing treatments do not work in brain metastasis, he went on to say, citing real data.

People can infer that small molecule drugs are more likely to penetrate the blood-brain barrier than antibody agents, and data proved that Nerlynx reduced brain metastasis significantly, he said.

“But Nerlynx’s most important treatment benefit is not about brain metastasis,” he added.

Lee stressed that raising patient access to Nerlynx was important.

Many patients have large residual tumors and lymph nodes even after receiving chemotherapy before surgery, and as a doctor, he feels frustrated, he said. However, these patients are the best group to receive a Nerlynx prescription.

“If a patient gets one-year Herceptin treatment and additional one-year Nerlynx therapy, the patient will suffer a financial burden. This is why I think Nerlynx should become reimbursable,” Lee said.

He did not forget to leave comments for breast cancer patients.

He urged hormone-positive breast cancer patients to get treatment at least for five years and up to 10 years.

“HER2 is a tumor with unique characteristics. As a result, the patient will have to live with anxiety for a long time,” Lee said. “That’s why patients should know the nature of this tumor exactly and receive treatment without getting tired for a long time.”