Roche Korea won approval for Tecentriq (ingredient: atezolizumab) in February to treat breast cancer as the nation’s first anti-PD-L1 immunotherapy in Korea.

Treatment options for metastatic triple-negative breast cancer (TNBC) have been limited except for chemotherapy, and TNBC has a poor prognosis. However, the combination of Tecentriq and chemotherapy has made a significant turning point for the TNBC treatment, experts said.

Korea Biomedical Review met Kim Sung-bae, head of the Breast Cancer Center at Asan Medical Center, to learn how local physicians treated TNBC and the implications of Tecentriq's approval. He was recently appointed as Scientific Committee Co-Chair of ESMO Breast Cancer Congress 2021, for the first time as an Asian.

Question: Treatment options have been significantly limited in TNBC, which gained rare attention compared with other types of breast cancer. What is TNBC, and how have physicians treat it?

Answer: TNBC refers to breast cancer that lacks the expression of receptors for estrogen, progesterone, and HER2. The disease accounts for about 15-20 percent of all breast cancer, and it has a higher incidence among young patients. TNBC patients have a high risk of metastasis to other organs, and the illness usually relapses one to three years after treatment.

Doctors have used aromatase inhibitors for hormone receptor-positive (HR+) breast cancer, and HER2-targeting therapies for HER2-positive breast cancer.
For TNBC, physicians have used chemotherapies such as adriamycin, taxanes, and capecitabine.

Q: Tecentriq arrived in the TNBC treatment market as the first immunotherapy. Can you share your thoughts on this?

A: As TNBC has strong immunogenicity, I expected that immunotherapy would work well. Usually, patients with TNBC often died within one to two months after receiving chemotherapy for the first 12 weeks, the second for nine weeks, and the third for four weeks.

However, only 10-20 percent of patients showed a response to immunotherapy, but some of their treatment went for over a year. Immunotherapies were effective in patients with PD-L1 positive and those with lots of tumor-infiltrating lymphocytes (TIL). So, physicians have discussed how to select these patients for immunotherapies.

Then, the phase-3 IMpassion130 study tested Tecentriq in TNBC patients. The trial outcomes showed that the combination of Tecentriq with paclitaxel doubled the median overall survival of patients to 25 months. If survival data improves by just one third, people usually say that the new drug changed the treatment paradigm. As the Tecentriq combo extended survival by more than two times, it was significant.

Q: But the Impassion130 study results showed that the Tecentriq combo extended the median overall survival only by about a half year. Considering the lowered quality of patient life, do you think the life extension was long enough?

A: Some people may wonder if extending life by only seven months would mean much, if not several years. But patients, whose end of life is imminent, can find it meaningful to have their remaining life doubled. No drug has improved the survival of TNBC patients so far.

According to the KEYNOTE-522 trial results announced during the American Society of Clinical Oncology meeting in May, another immunotherapy with chemotherapy also showed effectiveness. This indicates that immunotherapy plus chemotherapy has built medical evidence for TNBC patients.

Q: In Korea, Tecentriq widened the indication to TNBC in February. Do you feel any changes when you provide medical care?

A: I prescribe the Tecentriq combo for patients with PD-L1 positive because such a patient group showed a better treatment effect in the IMpassion130 study. The PD-L1 expression can be tested in most large hospitals. Ventana PD-L1 (SP142) Assay, an accompanying diagnostic test for Tecentriq, is covered by the national health insurance. Patients can check the results within two to three days.

However, Tecentriq, in combination with chemotherapy, is not reimbursable for TNBC in Korea. So, the prescription is limited in reality. But many patients participated in the Tecentriq combo trial and have done very well without disease progress for about 18 months to two years. Compared with the past, when such patients had only about one year left to live, this is a remarkable change.

Q: Do you think Tecentriq combo needs insurance benefits for TNBC treatment?

A: Health professionals make treatment guidelines by prioritizing which treatment can help patients and measuring the “magnitude of clinical benefit” provided by new drugs. When establishing treatment guidelines, the ASCO evaluates differently whether the treatment extended the survival by six months to one year, or by more than 50 percent compared to the existing standard of care.

There are many young people among TNBC patients. It means that they are more desperate for survival because they have the most active periods for social life and parenting. From the doctors' perspectives, the Tecentriq combo is significant because we are equipped with the proof that the therapy improved effectiveness in TNBC, which has been difficult to treat.