Keerthi Gogineni, MD, MSHP, an assistant professor, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, discusses the clinical implications of the phase II APT trial in HER2-positive breast cancer.

The APT trial, launched in 2015, and led by Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute, evaluated de-escalation strategies in women with small, node-negative HER2-positive breast cancer. Investigators evaluated a chemotherapy backbone of adjuvant paclitaxel in combination with trastuzumab (Herceptin). Notably, the 7-year disease-free survival rate (DFS) was 93%. This trial demonstrated that women with small, node-negative tumors could receive the regimen with manageable toxicity, while ensuring they are at low risk of relapse, says Gogineni.

Since then, several studies, including meta analyses, have evaluated a shorter duration of trastuzumab. For example, the phase III HERA trial evaluated a 24- and 12-month duration of trastuzumab versus observation, while the phase III PERSEPHONE trial examined a 6- and 12-month duration of the agent. Eleven years of follow-up from the HERA trial showed that 12 months of adjuvant trastuzumab significantly improved long-term DFS compared with observation, and 24 months of trastuzumab did not provide any additional benefit. PERSEPHONE showed noninferiority between the 6- and 12-month durations of trastuzumab.

However, these regimens are no longer commonplace in practice, and it may not be safe to de-escalate both the chemotherapy and the duration of trastuzumab, concludes Gogineni.

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Keerthi Gogineni, MD, MSHP, discusses the clinical implications of the phase II APT trial in HER2-positive breast cancer.

Dr. Gogineni on Implications of the APT Trial in HER2+ Breast Cancer

Keerthi Gogineni, MD, MSHP, an assistant professor in the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, discusses de-escalation strategies in HER2-positive breast cancer.

The phase III KRISTINE study, presented at the 2019 ASCO Annual Meeting by Sara Hurvitz, MD, looked at women who had larger stage II/III HER2-positive tumors. Investigators assessed whether ado-trastuzumab emtansine (T-DM1; Kadcyla) could be used in combination with pertuzumab (Perjeta) rather than the more toxic regimen composed of docetaxel/carboplatin/trastuzumab (Herceptin) plus pertuzumab (TCHP), without sacrificing efficacy.

The combination showed a lower rate of grade 3 toxicity than TCHP. However, event-free survival (EFS) appeared to be inferior in the T-DM1/pertuzumab arm. It looked like the inferior EFS was mostly driven by early progressors, which shed light on who is more likely to respond to the combination.

The patients who didn't progress before surgery were strongly HER2-positive, says Gogineni; these patients did well with TCHP. Furthermore, the rates of invasive disease-free survival are virtually inseparable. This presents a potential option for de-escalation for larger HER2-positive tumors, adds Gogineni. However, careful consideration of HER2 heterogeneity and HER2 expression will be necessary to ensure that the right population is being selected for de-escalated approaches.

Keerthi Gogineni, MD, MSHP

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Dr. Gogineni on Implications of the APT Trial in HER2+ Breast Cancer

Dr. Gogineni on De-Escalation Strategies in HER2+ Breast Cancer