Otprilike 1 od 3 bolesnice sa stadijem II (N0,N1) ER+ ranog raka dojke (eBC) doživjet će udaljeni recidiv - činjenica koja naglašava nemogućnost današnjeg liječenja da u potpunosti odgovori na potrebe ovih bolesnica.1,2
NEPREPOZNAT RIZIK
U HR+/HER2- eBC
Broj bolesnica sa stadijem II (N0, N1) bolesti i njihova razina rizika je značajna.2,3
Znatan udio bolesnica3
Procjena temeljena prema podatcima iz Surveillance, Epidemiology, and End Results (SEER) registra.
Klasifikacija TNM stadija II
Stadij II4
T (veličina tumora)4
N (broj zahvaćenih limfnih čvorova)5
IIA
T0 (nema dokaza primarnog tumora)
N1 (1 - 3)
IIA
T1 (≤2 cm)
N1 (1 - 3)
IIA
T2 (>2-≤5 cm)
N0 (0)
IIB
T2 (>2-≤5 cm)
N1 (1 -3)
IIB
T3 (>5 cm)
N0 (0)
Podcijenjen rizik2
Iako heterogena populacija, sve bolesnice sa stadijem II (N0, N1) ER+ eBC-a su u riziku od udaljenog recidiva.1,2,6
Broj bolesnica u riziku (i, u svakom razdoblju od 5 godina, broj događaja i godišnja stopa)
T1N1
17171 (1203, 1.5%)
13305 (652, 1.5%)
4282 (130, 1.6%)
552 (20, 1.5%)
102
T2N1
14765 (1923, 3.0%)
10271 (769, 2.5%)
2968 (111, 1.9%)
397 (19, 2.1%)
81
T2N0
10243 (902, 1.9%)
7974 (410, 1.6%)
2870 (119, 1.6%)
659 (29, 1.7%)
151
Okomite trakice označavaju 95% interval pouzdanosti (CI). Isprekidane linije označavaju stopu događanja tijekom 5 godina.
Iz meta-analize 78 randomiziranih ispitivanja the Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG) baze podataka 74,194 žena s ER+ karcinomom dojke koje su tijekom 5 godina primale endokrinu terapiju. Bolesnice s T0 i T3, i N3 bolesti, nisu bile uključene u analizu.¹
Vaše bolesnice sa stadijem II (N0, N1) eBC-a trebaju nove mogućnosti koje učinkovitije smanjuju rizik od recidiva
JAZ U LIJEČENJU
U HR+/HER2- eBC
Praznina u inovacijama u liječenju ostavlja većinu bolesnica sa stadijem II (N0, N1) bolesti bez optimalne terapije.7,8
Nedavno odobrene terapije ograničene su na visokorizično okruženje.7-10
Udio stadija II HR+/HER2- bolesti za koji se procjenjuje da će se riješiti nedavnim napretkom u liječenju.
Iako abemaciklib i olaparib pružaju dodatne mogućnosti, svaki je indiciran za uporabu u <15% bolesnica s eBC3,8,11,12
Postotci izračunati na temelju odobrenja abemacikliba za bolest stadija II ili III s pozitivnim limfnim čvorovima i, za olaparib, prevalencija mutacija BRCA1 i BRCA2 u ER+ raku dojke.
IZAZOVI PODNOŠLJIVOSTI
Podnošljivost i adherencija ostaju izazovi u HR+/HER2- ranom karcinomu dojke13-18
Simptomatske neželjene reakcije povezane su sa:
- Nemogućnosti obavljanja svakodnevnih životnih aktivnosti
- Nepridržavanjem liječenju
- Većim stopama prekida liječenja
U kliničkim ispitivanjima, novije opcije liječenja za HR+/HER2- eBC imale su veće stope simptomatskih neželjenih reakcija u usporedbi s placebom - osobito proljeva, mučnine i umora - što je doprinijelo prekidu u gotovo 1 od 5 bolesnica.7,19,20
Prekid liječenja i nepridržavanje povezani su s povećanim rizikom od recidiva, što naglašava potrebu za liječenjem s poboljšanom podnošljivošću14,21,22
UOČITE JAZ
Značajan rizik od udaljenog recidiva za bolesnice sa stadijem II (N0, N1) ranog karcinoma dojke (eBC) ostaje uglavnom neriješen današnjim tretmanima2,3,8,11,12,14,19-22
Neprepoznat rizik
Dijagnozu stadija II (N0, N1) ima značajan broj HR+/HER2- ranih karcinoma dojke i otprilike 1 od 3 bolesnice je u riziku od udaljenih recidiva.2,3
Jaz u liječenju
Nedavno odobrene terapije su ograničene u porabi na <15% bolesnica, ostavljajući većinu (N0, N1) bolesnica bez optimalne terapije.7-12
Izazovi podnošenja
Gotovo 1 od 5 bolesnica prekida ove terapije zbog problema s podnošljivošću — ostavljajući ih pod povećanim rizikom od recidiva.13-18
Novartis je predan uklanjanju ovog jaza u liječenju bolesnica sa stadijem II (N0, N1) HR+/HER2- eBC23,24
Kratice i reference
KRATICE:
- BRCA - engl. Breast Cancer gen
- eBC - engl. early Breast Cancer, rani karcinom dojke
- ER+ - estrogen receptor pozitivan
- ET - endokrina terapija
- gBRCAm - zametni mutirani Breast Cancer gen
- HER2– - negativan receptor za humani epidermalni faktor rasta tip 2
- HR+ – hormon receptor-pozitivan
- N - limfni čvor (broj limfnih čvorova)
- T - veličina tumora
REFERENCE:
- Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830
- Pan H, Gray R, Braybrooke J, et al; EBCTCG. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846;(suppl). doi:10.1056/NEJMoa1701830
- Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055
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- Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2–, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. doi:10.1200/JCO.20.02514
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- Verzenios [Summary of Product Characteristics]. Eli Lilly Nederland B.V.; 2023. Pristupljeno srpanj 2023. https://www.ema.europa.eu/en/documents/product-information/verzenios-epa...
- Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936
- Ahmed N, Vengalasetti Y, Haslam A, Prasad V. Association of adjuvant or metastatic setting with discontinuation of cancer drugs in clinical trials. JAMA Netw Open. 2022;5(5):e2212327. doi:10.1001/jamanetworkopen.2022.12327
- Pistilli B, Lohrisch C, Sheade J, Fleming GF. Personalizing adjuvant endocrine therapy for early-stage hormone receptor-positive breast cancer. Am Soc Clin Oncol Educ Book. 2022;42:60-72. doi:10.1200/EDBK_350358
- Smith KL, Verma N, Blackford AL, et al. Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation. NPJ Breast Cancer. 2022;8(1):53. doi:10.1038/s41523-022-00414-0
- Brett J, Fenlon D, Boulton M, et al. Factors associated with intentional and unintentional non-adherence to adjuvant endocrine therapy following breast cancer. Eur J Cancer Care (Engl). 2018;27(1). doi:10.1111/ecc.12601
- Fontein DBY, Nortier JWR, Liefers GJ, et al. High non-compliance in the use of letrozole after 2.5 years of extended adjuvant endocrine therapy. Results from the IDEAL randomized trial. Eur J Surg Oncol. 2012;38(2):110-117. doi:10.1016/j.ejso.2011.11.010
- Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120-4128. doi:10.1200/JCO.2009.25.9655
- Tutt ANJ, Garber JE, Kaufman B, et al; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215
- Rugo HS, O’Shaughnessy J, Boyle F, et al; monarchE Committee Members. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study. Ann Oncol. 2022;33(6):616-627. doi:10.1016/j.annonc.2022.03.006
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- A phase III, multicenter, randomized, open-label trial to evaluate efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, early breast cancer (New Adjuvant TriAl with Ribociclib [LEE011]: NATALEE). EduraCT identifier: 2018-002998-21. Posted January 18, 2019. Pristupljeno srpanj 2023. https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-002998-21/ES
- A trial to evaluate efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer (NATALEE). ClinicalTrials.gov identifier: NCT03701334. Updated February 18, 2022. Pristupljeno srpanj, 2023. https://clinicaltrials.gov/ct2/show/NCT03701334?term=NCT03701334&draw=2&...
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