Combination of Olaparib with radiotherapy for triple-negative breast cancers: One-year toxicity report of the RADIOPARP Phase I trial.
Adult
Aged
Combined Modality Therapy
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Hyperpigmentation
/ chemically induced
Middle Aged
Pain
/ chemically induced
Phthalazines
/ administration & dosage
Piperazines
/ administration & dosage
Poly(ADP-ribose) Polymerase Inhibitors
/ administration & dosage
Prospective Studies
Radiotherapy
/ methods
Radiotherapy Dosage
Treatment Outcome
Triple Negative Breast Neoplasms
/ drug therapy
Olaparib
breast cancer
breast radiotherapy
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
15 11 2021
15 11 2021
Historique:
revised:
05
06
2021
received:
05
05
2021
accepted:
07
07
2021
pubmed:
17
7
2021
medline:
23
11
2021
entrez:
16
7
2021
Statut:
ppublish
Résumé
Triple-negative breast cancer (TNBC) cells are sensitive to PARP1 inhibitors in vitro. The combination of Olaparib and radiotherapy for TNBC is currently evaluated in the Phase I RADIOPARP trial. RADIOPARP is a monocentric prospective open-label Phase I dose-escalation trial evaluating the combination of breast radiotherapy and Olaparib in TNBC patients with inflammatory, locoregionally advanced or metastatic disease, or with residual disease after neoadjuvant chemotherapy. Olaparib was orally given at increasing dose levels (50, 100, 150 or 200 mg twice a day [BID]); radiotherapy consisted of 50 Gy to the breast or chest wall with or without lymph node irradiation. Twenty-four TNBC patients were enrolled between September 2017 and November 2019. Olaparib was escalated to 200 mg BID without dose-limiting toxicities. At 1-year follow-up, no treatment-related grade ≥3 toxicity was observed. One patient (4.2%) had persistent grade 2 adverse events (breast pain, fibrosis and deformity). There was no cardiac, pulmonary or digestive toxicity related to treatment. The 1-year follow-up report of the RADIOPARP Phase I trial, evaluating Olaparib associated with breast radiotherapy in TNBC patients, consequently demonstrated an excellent toxicity profile of this combination with few low-grade adverse events.
Substances chimiques
Phthalazines
0
Piperazines
0
Poly(ADP-ribose) Polymerase Inhibitors
0
olaparib
WOH1JD9AR8
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1828-1832Informations de copyright
© 2021 UICC.
Références
Lin NU, Vanderplas A, Hughes ME, et al. Clinicopathological features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012;118(22):5463-5472.
Mehanna J, Haddad FG, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health. 2019;11:431-437.
Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-172.
Swisher SK, Vila J, Tucker SL, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23(3):749-756.
To C, Kim E-H, Royce DB, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res. 2014;7(7):698-707.
Chopra N, Tovey H, Pearson A, et al. Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer. Nat Commun. 2020;11(1):2662.
Lesueur P, Chevalier F, Austry J-B, et al. Poly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: a systematic review of pre-clinical and clinical human studies. Oncotarget. 2017;8(40):69105-69124.
Robson M, Im S-A, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523-533.
Loap P, Loirat D, Berger F, et al. Combination of olaparib and radiation therapy for triple negative breast cancer: preliminary results of the RADIOPARP phase 1 trial. Int J Radiat Oncol Biol Phys. 2021;109(2):436-440.
Cheung YK, Chappell R. Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics. 2000;56(4):1177-1182.
Paoletti X, Ezzalfani M, Le Tourneau C. Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials. Ann Oncol. 2015;26(9):1808-1812.
Kirova YM, Hijal T, Campana F, et al. Whole breast radiotherapy in the lateral decubitus position: a dosimetric and clinical solution to decrease the doses to the organs at risk (OAR). Radiother Oncol. 2014;110(3):477-481.
Grellier Adedjouma N, Chevrier M, Fourquet A, et al. Long-term results of a highly performing conformal electron therapy technique for chest wall irradiation after mastectomy. Int J Radiat Oncol Biol Phys. 2017;98(1):206-214.
Arsene-Henry A, Foy J-P, Robilliard M, et al. The use of helical tomotherapy in the treatment of early stage breast cancer: indications, tolerance, efficacy-a single center experience. Oncotarget. 2018;9(34):23608-23619.
Loap P, Kirova Y. Evaluating cardiac substructure radiation exposure in breast rotational intensity modulated radiation therapy: effects of cancer laterality, fractionation and deep inspiration breath-hold. Cancer Radiother. 2021;25(1):13-20.
Pons-Tostivint E, Kirova Y, Lusque A, et al. Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis. Radiother Oncol. 2020;145:109-116.
Pons-Tostivint E, Alouani E, Kirova Y, Dalenc F, Vaysse C. Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies?: evidences, unresolved questions and a practical algorithm. Crit Rev Oncol Hematol. 2021;157:103146.
Zhou JX, Feng LJ, Zhang X. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: a meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2017;11:3009-3017.
Campbell AC, Wiernik G, Wood J, Hersey P, Waller CA, Maclennan ICM. Characteristics of the lymphopenia induced by radiotherapy. Clin Exp Immunol. 1976;23(2):200-208.
Petersen C, Würschmidt F. Late toxicity of radiotherapy: a problem or a challenge for the radiation oncologist? Breast Care. 2011;6(5):369-374.
Jagsi R, Griffith KA, Bellon JR, et al. Concurrent veliparib with chest wall and nodal radiotherapy in patients with inflammatory or locoregionally recurrent breast cancer: the TBCRC 024 phase I multicenter study. J Clin Oncol. 2018;36(13):1317-1322.
Loap P, Kirov K, Kirova Y. Cardiotoxicity in breast cancer patients treated with radiation therapy: from evidences to controversies. Crit Rev Oncol Hematol. 2020;156:103121.
Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol. 2005;6(8):557-565.
Bekelman JE, Lu H, Pugh S, et al. Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol. BMJ Open. 2019;9(10):e025556.
Loap P, Beddok A, Cao KI, et al. Clinical practice of breast cancer protontherapy: a single-centre experience from selection to treatment. Cancer Radiother. 2021;25(4):358-365.
Ares C, Khan S, Macartain AM, et al. Postoperative proton radiotherapy for localized and locoregional breast cancer: potential for clinically relevant improvements? Int J Radiat Oncol Biol Phys. 2010;76(3):685-697.
Vitti ET, Parsons JL. The radiobiological effects of proton beam therapy: impact on DNA damage and repair. Cancers. 2019;11(7):946.