“KAITLIN didnot meet its primary endpoint, either in the intent-to-treat or node-positive population,1 but in context with the APHINITY trial [1 year of adjuvant pertuzumab/trastuzumab plus chemotherapy],2 whose outcomes were similar at 3 years, you can appreciate that both arms did extremely well,” said KAITLIN study invited discussant, Evandro de Azambuja, MD, PhD, Head of the Medical Support Team at the Institut Jules Bordet, Brussels.
Evandro de Azambuja, MD, PhD
The updated biomarker analysis showed that patients with IHC2+ or 3+ focal HER2 expression and patients with HER2 gene copy number of 4 to < 6 had better outcomes when treated with anthracycline plus trastuzumab/pertuzumab and paclitaxel. The number of events was small, however, so these findings should be interpreted with caution, he said.
No differences between the treatment arms were seen for PIK3CA mutations or median HER2 expression level, Dr. de Azambuja added. “No clear prognostic relationships were shown in the pooled arms, and there are no clinical implications for these findings,” he maintained.
The lack of a biomarker to predict response to anti-HER2 therapy was also shown in a systematic review that Dr. de Azambuja coauthored in 2017.3 “Beyond HER2 itself, you could not demonstrate any biomarker that has clinical utility in HER2-positive breast cancer,” he said. “Again, we need more research in this area to identify patients who really benefit from these drugs.”
As the substitution of trastuzumab emtansine for trastuzumab/paclitaxel did not improve efficacy outcomes, the regimen of anthracyclines plus taxane and pertuzumab/trastuzumab remains the standard of care for the high-risk HER2-positive early breast cancer population, he said, adding that clinicians should also consider nonanthracycline-based regimens at this time.
DISCLOSURE: Dr. de Azambuja reported financial relationships with Roche/GNE, GSK/Novartis, Seattle Genetics, Libbs, Zodiac, Lilly, and Pierre Fabre; has been reimbursed for travel, accommodations, or other expenses from Roche/GNE and GSK/Novartis; and has receieved institutional research funding from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier.
1. Metzger O, Lambertini, Krop IE, et al: Biomarker analysis from KAITLIN, a randomised phase III study of adjuvant trastuzumab emtansine plus pertuzumab versus trastuzumab plus taxane plus pertuzumab after anthracyclines for high-risk HER2-positive early breast cancer. ESMO Breast Cancer Virtual Congress 2021. Abstract 420. Presented May 7, 2021.
2. Piccart M, Procter M, Fumagalli D, et al: Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer in the APHINITY trial: 6 Years’ follow-up. J Clin Oncol 39:1448-1457, 2021.
3. Gingras I, Gebhart G, de Azambuja E, et al: HER2-positive breast cancer is lost in translation. Nat Rev Clin Oncol 14:669-681, 2017.
In the phase III KAITLIN trial, replacing adjuvant taxane and trastuzumab with ado-trastuzumab emtansine (T-DM1) did not result in a significant improvement in invasive disease–free survival in the node-positive or intent-to-treat population of women with high-risk, HER2-positive early breast...