In honor of breast cancer awareness month, it seems fitting to highlight recent gains related to an aggressive subtype of the disease that has typically been difficult to treat. Triple Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancers, and it is usually found in women under 40, who have BRCA1 mutation, or are black.[1] The KEYNOTE-355 and KEYNOTE-522 clinical trials concluded that Pembrolizumab (brand name KETRUDA) used together with chemotherapy increased the overall survival in patients. Based on these studies, the FDA approved KEYTRUDA for two indications:

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.[2] (FDA Approval Date 7/26/2021)

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.[2, 3] (FDA Approval Date 11/13/2020)

It is important to remember, however, that results may vary significantly, particularly because the diversity of the of the patient group. Nonetheless, this advancement offers a positive advance in treatment for those affected.

Articles related to the KEYNOTE-355 Clinical Study:

1) Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Torregroza Otero M, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022 Jul 21;387(3):217-226. doi: 10.1056/NEJMoa2202809.

2) Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. doi: 10.1016/S0140-6736(20)32531-9.

Articles related to the KEYNOTE-522 Clinical Study:

1) Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O'Shaughnessy J; KEYNOTE-522 Investigators. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022 Feb 10;386(6):556-567. doi: 10.1056/NEJMoa2112651.

2) Pérez-García J, Soberino J, Racca F, Gion M, Stradella A, Cortés J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25. Review.

3) Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

Article written by Kathy Clark, RN, BSN, CMCN, RIT, Vice President, Managed Care for Summit Reinsurance Services, Inc. For more information about how this may affect your plan, please contact your Summit ReSources care specialist. In addition to the citations above, the following sources were used as reference material for this article:

[1] Triple Negative Breast Cancer. https://www.cancer.org/cancer/breast-cancer/about/types-of-breast-cancer/triple-negative.html

[2]1.18 Triple-Negative Breast Cancer. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s133lbl.pdf

[3] 2.1 Patient Selection. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s133lbl.pdf

Summit Perspectives