Recurrent and Metastatic HER2-Positive Breast Cancer, New Treatment Method with Reduced Side Effects Gains Attention

Korean Cancer Chemotherapy Study Group; Announcement of Phase 2 Results of 'Neo-PATH' Clinical Trial
Replacing Conventional Chemotherapy with Immuno-Oncology Drugs... Reduced Side Effects and Confirmed Treatment Efficacy

[Asia Economy Reporter Lee Gwan-joo] Attention is focused on whether a new treatment method can emerge to reduce side effects while maintaining therapeutic efficacy in patients with HER2 receptor-positive breast cancer.

A research team led by Professors Park Yeon-hee and Kim Ji-yeon from the Department of Hematology and Oncology at Samsung Seoul Hospital, Professor Jung Kyung-hae from the Department of Oncology at Seoul Asan Hospital, and Professor Ahn Hee-kyung from the Department of Oncology at Gil Hospital announced the results of the Phase 2 'Neo-PATH clinical study,' conducted by the Breast Cancer Subcommittee of the Korean Cancer Chemotherapy Study Group (KCGS) in collaboration with six domestic institutions.

Among the various types of breast cancer, HER2-positive breast cancer accounts for about 20% of all breast cancer patients. It is known to have a higher recurrence rate and poorer prognosis compared to other breast cancers. Therefore, to improve patient survival rates, it is common to perform ‘TCHP neoadjuvant chemotherapy,’ which combines cytotoxic chemotherapy agents (docetaxel, carboplatin) and targeted therapies (trastuzumab, pertuzumab) before surgery. This approach shows a high complete response rate and is used as the standard treatment.

With a complete pathological response rate reaching 50-60% after treatment, this method has recently gained attention in clinical practice. However, the increased efficacy is accompanied by heightened toxicity from the cytotoxic chemotherapy agents. Normal dividing cells such as bone marrow cells and gastric mucosal cells are attacked, leading to frequent grade 3 or higher diarrhea that can progress to sepsis. Peripheral neuropathy also occurs frequently, making it difficult to actively administer TCHP chemotherapy to elderly patients or those with other comorbidities.

The research team found a breakthrough in the recently spotlighted immune checkpoint inhibitors. They removed carboplatin, one of the cytotoxic chemotherapy agents, from the existing regimen and replaced it with the immune checkpoint inhibitor atezolizumab. Under the auspices of the Korean Cancer Chemotherapy Study Group, the team applied the new treatment method ‘Neo-PATH’ to 67 HER2 receptor-positive patients recruited from six domestic medical institutions between May 2019 and May 2020 and conducted follow-up observations.

The average age of the patients was 52 years, and the breast tumors were larger than 2 cm. These patients were clinically staged as stage 2 to 3 breast cancer and were candidates for neoadjuvant chemotherapy. According to the new treatment protocol, patients received six cycles of neoadjuvant chemotherapy at three-week intervals, after which 65 patients underwent surgery, excluding two whose cancer progressed. Post-surgery, cytotoxic chemotherapy agent docetaxel was discontinued, and only targeted therapy and immune checkpoint inhibitors were administered for an additional 12 to 14 cycles.

As a result, 61% of patients who completed the chemotherapy reached a complete pathological response. Side effects were evaluated to be relatively safe. Muscle pain (75%) was the most common, followed by hair loss (67%) and rash (64%). Moderate or higher grade neutropenia and febrile neutropenia occurred in only 12% and 5% of patients, respectively. Notably, immune-related adverse events were observed in 6%, showing results similar to other studies.

As the combination of immune checkpoint inhibitors has just begun to demonstrate efficacy in triple-negative breast cancer, this study provides a basis for hopeful expectations in HER2-positive breast cancer as well. However, since this was a Phase 2 study with a small patient population and no control group, the research team emphasized the need for further studies to supplement the evidence.

Professor Park Yeon-hee explained, “Although the prognosis of HER2-positive breast cancer patients has improved since the development of targeted therapies, many challenges remain. Considering the frequent recurrence and metastasis, more ‘weapons’ are needed to fight breast cancer. This study was conducted to find such clues.”

This study was published in the recent issue of ‘JAMA Oncology’ (IF=31.777), one of the world’s leading journals in clinical oncology.

This content was produced with the assistance of AI translation services.