Guideline Update Offers New Directions About Trastuzumab Emtansine for HER2-Positive Breast Cancer

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About 10% to 20% of newly diagnosed breast cancers demonstrate overexpression of the HER2 protein.1 Since the introduction of trastuzumab, several new HER2-targeted therapies have been approved for use in the adjuvant and metastatic settings (eg, pertuzumab, lapatinib, and neratinib). However, for some women, disease recurrence occurs, and ongoing research continues to seek optimal therapeutics to give all women with HER2-positive disease the greatest chances at survival.

In 2018, ASCO published an update2 to its 2016 adaptation3 of the Cancer Care Ontario guideline4 on the use of adjuvant chemotherapy for early-stage breast cancer and targeted therapy for HER2-positive disease. However, recent data from the phase III KATHERINE trial5—which enrolled patients without a complete response to treatment in the neoadjuvant setting—shed new light on how best to treat women with residual disease. Thus, ASCO again enlisted a multidisciplinary group of experts to revise the guideline to account for these new findings.6

Sharon H. Giordano, MD, MPH, FASCO

Sharon H. Giordano, MD, MPH, FASCO

“The KATHERINE trial was identified by panel members and a systematic literature review as a practice-changing study that warranted a focused guideline update,” said expert panel Co-Chair Sharon H. Giordano, MD, MPH, FASCO, of The University of Texas MD Anderson Cancer Center. “In KATHERINE, patients with HER2-positive breast cancer with residual invasive disease after completing neoadjuvant chemotherapy and HER2-targeted therapy were randomly assigned to adjuvant trastuzumab emtansine [T-DM1] or to trastuzumab. Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab arm, and risk of distant recurrence was lower in patients who received T-DM1.”

Expanding the Scope of the Guideline

Based on these encouraging findings, the panel revisited the literature on whether the antibody-drug conjugate T-DM1 should be the standard-of-care following preoperative chemotherapy and HER2-targeted therapy in all patients with HER2-positive breast cancer with residual invasive cancer in the breasts or lymph nodes at surgery. The ASCO panel also decided, based in part on input from members of ASCO’s Breast Cancer Guideline Advisory Group, to expand the guideline update scope to address the use of biosimilar forms of trastuzumab, because five trastuzumab biosimilars have been approved by the U.S. Food and Drug Administration. The discovery of potentially effective biosimilar medications for trastuzumab could be especially meaningful for patients given the current high cost of the medication (approximately $70,000 for 1 year of trastuzumab treatment in the United States).7

For guideline updates, ASCO uses a “signals” approach, where a targeted systematic literature review and input from the panel identifies new practice-changing data (called “signals”). For this review, the KATHERINE trial provided the only signal, but the outcomes were so compelling that, based on this trial alone, ASCO’s Breast Cancer Advisory Group considered revising recommendations for adjuvant care a high priority.

Key Recommendations

The main recommendations from the focused update are that 14 cycles of adjuvant T-DM1 should be offered to patients with HER2-positive breast cancer with pathologic invasive residual disease after preoperative chemotherapy unless there is disease recurrence or unmanageable toxicity. Although the KATHERINE trial found that 25% of patients on T-DM1 experienced grade 3 or higher adverse events (compared with 15% of patients who received trastuzumab), the panel believed the evidence was strong, and the benefits outweighed the risks.

Dr. Giordano concurred that the use of T-DM1 is a significant advance in the treatment of HER2-positive breast cancer. “Patients with residual disease after preoperative chemotherapy are at a higher risk of recurrence. The use of T-DM1 was associated with a 50% higher invasive disease–free survival for these patients,” she said. “These recommendations for T-DM1 provide a way for patients with a higher risk of recurrence to further reduce their risk and to have better outcomes.”

Finally, the updated guideline recommends that any available formulations of trastuzumab biosimilars (ie, trastuzu­mab-dkst, trastuzumab-pkrb, trastuzumab-anns, trastuzumab-dttb, and trastuzumab-qyyp) may be used by clinicians, given that they have comparable safety and efficacy to trastuzumab. However, the guideline encourages oncologists to remain educated about biosimilars and to ensure patients are also aware of their safety, effectiveness, and potential risks. Future research will be necessary to better understand biosimilars and their long-term safety and effectiveness profiles as they become more widely used in clinics.

Both guideline recommendations help give oncologists additional effective tools for optimizing long-term survival and minimizing recurrence in women with HER2-positive disease.

“These data from the KATHERINE trial are another step forward for treating HER2-positive breast cancer and providing a way to meaningfully reduce risk of recurrence,” Dr. Giordano said. “We hope this guideline update will reinforce the practice of providing adjuvant T-DM1 for patients with HER2-positive breast cancer who have residual disease after chemotherapy.” 

DISCLOSURE: Dr. Giordano reported no conflicts of interest.


1. HER2 Status. Updated January 29, 2020. Available at Accessed September 27, 2020.

2. Denduluri N, Chavez-MacGregor M, Telli ML, et al: Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol 36:2433-2443, 2018.

3. Denduluri N, Somerfield MR, Eisen A, et al: Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: An ASCO Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline. J Clin Oncol 34:2416-2427, 2016.

4. Eisen A, Fletcher GG, Gandhi S, et al: Optimal systemic therapy for early breast cancer in women: A clinical practice guideline. Curr Oncol 22(suppl 1):S67-S81, 2015.

5. von Minckwitz G, Huang CS, Mano MS, et al: Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380:617-628, 2019.

6. Denduluri N, Somerfield MR, Chavez-MacGregor M, et al: Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO Guideline Update. J Clin Oncol. October 20, 2020 (early release online).

7. Nordqvist C: One year on Herceptin for breast cancer ideal. Medical News Today. October 1, 2012. Available at Accessed October 27, 2020.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, October 21, 2020. All rights reserved.