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TBCRC 030: A phase II study of preoperative cisplatin vs. paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker
- Source :
- Ann Oncol
- Publication Year :
- 2020
-
Abstract
- Background Cisplatin and paclitaxel are active in triple-negative breast cancer (TNBC). Despite different mechanisms of action, effective predictive biomarkers to preferentially inform drug selection have not been identified. The homologous recombination deficiency (HRD) assay (Myriad Genetics, Inc.) detects impaired double-strand DNA break repair and may identify patients with BRCA1/2-proficient tumors that are sensitive to DNA-targeting therapy. The primary objective of TBCRC 030 was to detect an association of HRD with pathologic response [residual cancer burden (RCB)-0/1] to single-agent cisplatin or paclitaxel. Patients and methods This prospective phase II study enrolled patients with germline BRCA1/2 wild-type/unknown stage I–III TNBC in a 12-week randomized study of preoperative cisplatin or paclitaxel. The HRD assay was carried out on baseline tissue; positive HRD was defined as a score ≥33. Crossover to an alternative chemotherapy was offered if there was inadequate response. Results One hundred and thirty-nine patients were evaluable for response, including 88 (63.3%) who had surgery at 12 weeks and 51 (36.7%) who crossed over to an alternative provider-selected preoperative chemotherapy regimen due to inadequate clinical response. HRD results were available for 104 tumors (74.8%) and 74 (71.1%) were HRD positive. The RCB-0/1 rate was 26.4% with cisplatin and 22.3% with paclitaxel. No significant association was observed between HRD score and RCB response to either cisplatin [odds ratio (OR) for RCB-0/1 if HRD positive 2.22 (95% CI: 0.39–23.68)] or paclitaxel [OR for RCB-0/1 if HRD positive 0.90 (95% CI: 0.19–4.95)]. There was no evidence of an interaction between HRD and pathologic response to chemotherapy. Conclusions In this prospective preoperative trial in TNBC, HRD was not predictive of pathologic response. Tumors were similarly responsive to preoperative paclitaxel or cisplatin chemotherapy.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Paclitaxel
medicine.medical_treatment
Phases of clinical research
Triple Negative Breast Neoplasms
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Medicine
Humans
Prospective Studies
Homologous Recombination
Triple-negative breast cancer
Cisplatin
Chemotherapy
business.industry
Hematology
medicine.disease
Neoadjuvant Therapy
Regimen
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Mutation
Biomarker (medicine)
business
Biomarkers
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Ann Oncol
- Accession number :
- edsair.doi.dedup.....fd4d430b47b75126d84acfb82d53273f