KEY TAKEAWAYS
- The phase III KAITLIN study aimed to enhance the effectiveness and minimize the harmful effects of treatment for HER2-positive early breast cancer by comparing two treatment regimens.
- The coprimary endpoints of the study were IDFS in the intention-to-treat node-positive and overall populations, with hierarchical testing.
- The study’s primary endpoint, which was to demonstrate the superiority of one treatment regimen over the other, still needs to be achieved.
Researcher’s objective was to enhance the effectiveness and minimize the harmful effects of treatment for high-risk human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) by substituting taxanes and trastuzumab with trastuzumab emtansine (T-DM1). The phase III KAITLIN study enrolled adult patients diagnosed with surgically removed HER2-positive early-stage breast cancer (either with or without lymph node involvement, negative for hormone receptors, and tumor size greater than 2.0 cm). Following surgical intervention, individuals were randomly allocated in a 1:1 ratio to receive anthracycline-based chemotherapy (consisting of three to four cycles) followed by 18 cycles of T-DM1 in combination with pertuzumab (referred to as AC-KP) or taxane (also three to four cycles) in combination with trastuzumab and pertuzumab (referred to as AC-THP). Adjuvant radiotherapy/endocrine therapy was authorized.
The co-primary endpoints of this study were invasive disease-free survival (IDFS) in the intention-to-treat node-positive and overall populations, with hierarchical testing. The median follow-up duration was 57.1 months (interquartile range, 52.1-60.1 months) for patients receiving AC-THP (n = 918) and 57.0 months (interquartile range, 52.1-59.8 months) for patients receiving AC-KP (n = 928). There was no statistically significant difference in the IDFS (invasive disease-free survival) between the study groups in patients with positive lymph nodes (n = 1,658; stratified hazard ratio [HR], 0.97; 95% CI, 0.71 to 1.32) or the overall population (n = 1,846; stratified HR, 0.98; 95% CI, 0.72 to 1.32). In the general population, the three-year invasive disease-free survival (IDFS) rate 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. The completion rates (i.e., 18 cycles) were 88.4% for AC-THP and 65.0% for AC-KP (the difference in rates was primarily due to discontinuation of T-DM1 treatment because of laboratory abnormalities, accounting for 12.5% of cases).
Comparable frequencies of grade ≥ 3 (55.4% versus 51.8%) and serious adverse events (23.3% versus 21.4%) were observed in patients receiving AC-THP and AC-KP, respectively. The use of KP significantly reduced overall health status deterioration compared to THP (stratified hazard ratio, 0.71; 95% CI, 0.62 to 0.80). The primary endpoint was not achieved. Both upper extremities exhibited favorable invasive disease-free survival (IDFS) outcomes. Trastuzumab, in combination with pertuzumab and chemotherapy, continues to be the established treatment protocol for high-risk early-stage breast cancer with HER2-positive status.
Source: https://pubmed.ncbi.nlm.nih.gov/34890214/
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT01966471
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. 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. J Clin Oncol. 2022 Feb 10;40(5):438-448. doi: 10.1200/JCO.21.00896. Epub 2021 Dec 10. PMID: 34890214; PMCID: PMC8824393.
