Combination of Olaparib with radiotherapy for triple‐negative breast cancers: One‐year toxicity report of the RADIOPARP Phase I trial. Issue 10 (26th July 2021)

• Record Type: Journal Article
• Authors: Loap, Pierre; Loirat, Delphine; Berger, Frederique; Cao, Kim; Ricci, Francesco; Jochem, Anne; Raizonville, Laurence; Mosseri, Veronique; Fourquet, Alain; Kirova, Youlia
• Is Part Of: International journal of cancer. Volume 149:Issue 10(2021)
• Page Start: 1828
• Page End: 1832
• Publication Date: 2021-07-26
• Subjects: breast cancer -- breast radiotherapy -- Olaparib; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33737
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: 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. Abstract : What's new? Patients with resectable triple‐negative breast cancer (TNBC) who experience non‐complete pathological response after neoadjuvant chemotherapy may benefit from radiosensitization to poly(ADP‐ribose) polymerase (PARP) inhibitors, owing to a phenomenon known as synthetic lethality. The present report describes results from the phase I RADIOPARP trial, in which radiotherapy was evaluated in combination with the PARP inhibitor olaparib for TNBC patients with advanced disease or residual disease after neoadjuvant chemotherapy. Among 24 patients in the trial, only one experienced persistent grade 2 adverse events at one‐year follow‐up. The promising one‐year toxicity profile warrants further study of combined radiotherapy and olaparib treatment for TNBC.