Tucatinib
The addition of tucatinib, a small molecule HER2 kinase inhibitor, to capecitabine and trastuzumab can prolong progression-free survival in patients with advanced HER2-positive breast cancer.[414]Curigliano G, Mueller V, Borges V, et al. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022 Mar;33(3):321-9.
https://www.annalsofoncology.org/article/S0923-7534(21)04879-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34954044?tool=bestpractice.com
The European Medicines Agency has approved tucatinib for treatment of locally advanced and metastatic HER2-positive breast cancer.
Lapatinib
Lapatinib, an oral dual tyrosine kinase inhibitor, improved pathologic complete response when used as neoadjuvant HER2-targeted therapy (as a single agent or combined with trastuzumab) in phase 3 trials of patients with HER2-positive invasive breast cancer.[415]Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.
Lancet. 2012 Feb 18;379(9816):633-40.
http://www.ncbi.nlm.nih.gov/pubmed/22257673?tool=bestpractice.com
[416]Untch M, von Minckwitz G, Gerber B, et al. Survival analysis after neoadjuvant chemotherapy with trastuzumab or lapatinib in patients with human epidermal growth factor receptor 2-positive breast cancer in the GeparQuinto (G5) study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-16.
http://www.ncbi.nlm.nih.gov/pubmed/29543566?tool=bestpractice.com
Lapatinib is associated with significant adverse events such as diarrhea, rash, and liver test abnormalities.[415]Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial.
Lancet. 2012 Feb 18;379(9816):633-40.
http://www.ncbi.nlm.nih.gov/pubmed/22257673?tool=bestpractice.com
Eganelisib
Phase 2 trials are investigating the addition of the checkpoint inhibitor eganelisib to chemotherapy for triple-negative, locally advanced, inoperable breast cancer.[417]ClinicalTrials.gov. Evaluation of IPI-549 combined with front-line treatments in patients with triple-negative breast cancer or renal cell carcinoma (MARIO-3). Aug 2023 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03961698
Eganelisib has been granted fast track designation by the Food and Drug Administration (FDA).
Partial breast irradiation with intraoperative radiation therapy
Intraoperative radiation therapy may allow radiation therapy with reduced toxicity to be completed at the same time as lumpectomy in highly selected patients with early breast cancer. However, studies suggest it may be associated with a higher rate of recurrence compared with whole-breast radiation therapy (with comparable overall mortality).[376]Shumway DA, Corbin KS, Farah MH, et al. Partial breast irradiation compared with whole breast irradiation: a systematic review and meta-analysis. J Natl Cancer Inst. 2023 Sep 7;115(9):1011-9.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10483267
http://www.ncbi.nlm.nih.gov/pubmed/37289549?tool=bestpractice.com
[418]Orecchia R, Veronesi U, Maisonneuve P, et al. Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial. Lancet Oncol. 2021 May;22(5):597-608.
http://www.ncbi.nlm.nih.gov/pubmed/33845035?tool=bestpractice.com
[419]Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61950-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/24224997?tool=bestpractice.com
Guidelines recommend that intraoperative radiation therapy for partial breast irradiation is used only as part of a clinical trial.[360]Shaitelman SF, Anderson BM, Arthur DW, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2024 Mar-Apr;14(2):112-32.
https://www.practicalradonc.org/article/S1879-8500(23)00296-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37977261?tool=bestpractice.com
[420]National Institute for Health and Care Excellence. Intrabeam radiotherapy system for adjuvant treatment of early breast cancer. Jan 2018 [internet publication].
https://www.nice.org.uk/guidance/ta501
Further research is needed to optimize patient selection criteria and treatment techniques.