Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study

Author(s): Ian E. Krop, MD1; Seock-Ah Im, MD2; Carlos Barrios, MD3; Hervé Bonnefoi, MD4; Julie Gralow, MD5; Masakazu Toi, MD6;
Source: J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10.
Lucio Gordan MD

Dr. Gordan's Thoughts

Negative study that documents failure of accretive benefit of TDM1/pertuzumab over trastuzumab/pertuzumab. Exploration of other pathways or target/payload will be necessary for clinical improvement/risk reduction of recurrence.

PURPOSE

We aimed to improve efficacy and reduce toxicity of high-risk human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (EBC) treatment by replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1).

METHODS

The phase III KAITLIN study (NCT01966471) included adults with excised HER2-positive EBC (node-positive or node-negative, hormone receptor–negative, and tumor > 2.0 cm). Postsurgery, patients were randomly assigned 1:1 to anthracycline-based chemotherapy (three-four cycles) and then 18 cycles of T-DM1 plus pertuzumab (AC-KP) or taxane (three-four cycles) plus trastuzumab plus pertuzumab (AC-THP). Adjuvant radiotherapy/endocrine therapy was permitted. Coprimary end points were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations with hierarchical testing.

RESULTS

The median follow-up was 57.1 months (interquartile range, 52.1-60.1 months) for AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for AC-KP (n = 928). There was no significant IDFS difference between arms in the node-positive (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or overall population (n = 1846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the overall population, the three-year IDFS was 94.2% (95% CI, 92.7 to 95.8) for AC-THP and 93.1% (95% CI, 91.4 to 94.7) for AC-KP. Treatment completion rates (ie, 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (difference driven by T-DM1 discontinuation because of laboratory abnormalities [12.5%]). Similar rates of grade ≥ 3 (55.4% v 51.8%) and serious adverse events (23.3% v 21.4%) occurred with AC-THP and AC-KP, respectively. KP decreased clinically meaningful deterioration in global health status versus THP (stratified HR, 0.71; 95% CI, 0.62 to 0.80).

CONCLUSION

The primary end point was not met. Both arms achieved favorable IDFS. Trastuzumab plus pertuzumab plus chemotherapy remains the standard of care for high-risk HER2-positive EBC.

Author Affiliations

1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. 2Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. 3Oncology Research Unit, Oncoclínicas, HSL, PUCRS, Porto Alegre, Brazil. 4Institut Bergonié Unicancer and Bordeaux University, Bordeaux, France. 5University of Washington, Seattle, WA. 6Graduate School of Medicine, Kyoto University, Kyoto, Japan.

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