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Annals of Oncology : Official Journal... Apr 2019In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients with a... (Comparative Study)
Comparative Study Randomized Controlled Trial
OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.
BACKGROUND
In the OlympiAD study, olaparib was shown to improve progression-free survival compared with chemotherapy treatment of physician's choice (TPC) in patients with a germline BRCA1 and/or BRCA2 mutation (BRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). We now report the planned final overall survival (OS) results, and describe the most common adverse events (AEs) to better understand olaparib tolerability in this population.
PATIENTS AND METHODS
OlympiAD, a Phase III, randomized, controlled, open-label study (NCT02000622), enrolled patients with a germline BRCAm and HER2-negative mBC who had received ≤2 lines of chemotherapy for mBC. Patients were randomized to olaparib tablets (300 mg bid) or predeclared TPC (capecitabine, vinorelbine, or eribulin). OS and safety were secondary end points.
RESULTS
A total of 205 patients were randomized to olaparib and 97 to TPC. At 64% data maturity, median OS was 19.3 months with olaparib versus 17.1 months with TPC (HR 0.90, 95% CI 0.66-1.23; P = 0.513); median follow-up was 25.3 and 26.3 months, respectively. HR for OS with olaparib versus TPC in prespecified subgroups were: prior chemotherapy for mBC [no (first-line setting): 0.51, 95% CI 0.29-0.90; yes (second/third-line): 1.13, 0.79-1.64]; receptor status (triple negative: 0.93, 0.62-1.43; hormone receptor positive: 0.86, 0.55-1.36); prior platinum (yes: 0.83, 0.49-1.45; no: 0.91, 0.64-1.33). Adverse events during olaparib treatment were generally low grade and manageable by supportive treatment or dose modification. There was a low rate of treatment discontinuation (4.9%), and the risk of developing anemia did not increase with extended olaparib exposure.
CONCLUSIONS
While there was no statistically significant improvement in OS with olaparib compared to TPC, there was the possibility of meaningful OS benefit among patients who had not received chemotherapy for metastatic disease. Olaparib was generally well-tolerated, with no evidence of cumulative toxicity during extended exposure. Please see the article online for additional video content.
Topics: Administration, Oral; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; BRCA1 Protein; Breast Neoplasms; Female; Follow-Up Studies; Germ-Line Mutation; Humans; Middle Aged; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Receptor, ErbB-2; Tablets
PubMed: 30689707
DOI: 10.1093/annonc/mdz012 -
Lancet (London, England) Apr 2016A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control).
METHODS
We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue.
FINDINGS
Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators.
INTERPRETATION
Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma.
FUNDING
Eisai.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Dacarbazine; Female; Furans; Humans; Ketones; Leiomyosarcoma; Liposarcoma; Male; Middle Aged; Neoplasm Grading; Soft Tissue Neoplasms; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 26874885
DOI: 10.1016/S0140-6736(15)01283-0 -
Journal of Clinical Oncology : Official... Feb 2015This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast... (Randomized Controlled Trial)
Randomized Controlled Trial
Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane.
PURPOSE
This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC).
PATIENTS AND METHODS
Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS).
RESULTS
Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2.
CONCLUSION
In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.
Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Capecitabine; Deoxycytidine; Female; Fluorouracil; Furans; Humans; Ketones; Middle Aged; Taxoids; Young Adult
PubMed: 25605862
DOI: 10.1200/JCO.2013.52.4892 -
Future Oncology (London, England) Nov 2023Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The...
Despite recent treatment advances, the prognosis for patients with locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC) remains poor. The antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via a stable, cleavable linker. The phase III TROPION-Breast02 trial in patients previously untreated for locally recurrent inoperable or metastatic TNBC, who are not candidates for PD-1/PD-L1 inhibitors is evaluating efficacy and safety of Dato-DXd versus investigator's choice of chemotherapy (ICC). Approximately 600 patients will be randomized 1:1 to Dato-DXd 6 mg/kg iv. every 3 weeks or ICC (paclitaxel, nab-paclitaxel, carboplatin, capecitabine or eribulin mesylate). Dual primary end points are progression-free survival by blinded independent central review and overall survival.
Topics: Humans; Female; Triple Negative Breast Neoplasms; Breast Neoplasms; Antineoplastic Agents; Prognosis; Antibodies, Monoclonal, Humanized; Immunoconjugates; Receptor, ErbB-2
PubMed: 37526149
DOI: 10.2217/fon-2023-0228 -
NPJ Breast Cancer Aug 2022Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer...
Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate with an SN-38 payload. In the ASCENT study, patients with metastatic triple-negative breast cancer (mTNBC) relapsed/refractory to ≥2 prior chemotherapy regimens (≥1 in the metastatic setting), received SG or single-agent treatment of physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine). This ASCENT safety analysis includes the impact of age and UGT1A1 polymorphisms, which hinder SN-38 detoxification. SG demonstrated a manageable safety profile in patients with mTNBC, including those ≥65 years; neutropenia/diarrhea are key adverse events (AE). Patients with UGT1A1 *28/*28 genotype versus those with 1/*28 and *1/*1 genotypes had higher rates of grade ≥3 SG-related neutropenia (59% vs 47% and 53%), febrile neutropenia (18% vs 5% and 3%), anemia (15% vs 6% and 4%), and diarrhea (15% vs 9% and 10%), respectively. Individuals with UGT1A1 *28/*28 genotype should be monitored closely; active monitoring and routine AE management allow optimal therapeutic exposure of SG.
PubMed: 36038616
DOI: 10.1038/s41523-022-00467-1 -
Nature Communications May 2022In the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer...
In the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer (TNBC). In this multicentered phase II trial (NCT04303741), 46 patients with pretreated advanced TNBC were enrolled to receive camrelizumab 200 mg (day 1), and apatinib 250 mg daily, plus eribulin 1.4 mg/m (day 1 and 8) on a 21-day cycle until progression, or unacceptable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included toxicities, disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), and 1-year overall survival. With a median of 3 lines of prior chemotherapy in the advanced setting, 17.4% had received PD-1/PD-L1 blockade plus chemotherapy for advanced disease. The ORR was 37.0% (17/46, 95% CI 23.2-52.5). The DCR was 87.0% (40/46, 95% CI 73.7-95.1). Median PFS was 8.1 (95% CI 4.6-10.3) months. Tertiary lymphoid structure was associated with higher ORR. Patients with lower tumor PML or PLOD3 expression had favorable ORR and PFS. PD-L1 status was not associated with ORR/PFS. Grade 3/4 treatment-related adverse events occurred in 19 (41.3%) of 46 patients. Camrelizumab plus apatinib and eribulin shows promising efficacy with a measurable safety profile in patients with heavily pretreated advanced TNBC.
Topics: Antibodies, Monoclonal, Humanized; B7-H1 Antigen; Furans; Humans; Ketones; Pyridines; Triple Negative Breast Neoplasms
PubMed: 35641481
DOI: 10.1038/s41467-022-30569-0 -
South Asian Journal of Cancer Jan 2014Eribulin is an anticancer drug approved for treatment of metastatic breast cancer. This drug is a synthetic derivative from Japanese marine sponge Halichondria okadai.... (Review)
Review
Eribulin is an anticancer drug approved for treatment of metastatic breast cancer. This drug is a synthetic derivative from Japanese marine sponge Halichondria okadai. It acts by interfering with the microtubular growth ultimately leading to apoptosis after prolonged mitotic blockage. In patients with metastatic breast cancer refractory to anthracyclines and taxanes, eribulin is one of the life-saving options. Neutropenia, neuropathy and QT prolongation are the most frequent adverse events associated with this drug. Phase I/II trials are also underway in refractory lung, ovarian, pancreatic, bladder, and soft tissue tumors. Larger prospective studies will define the role of this drug in a wide variety of tumors, and the future looks very promising.
PubMed: 24665449
DOI: 10.4103/2278-330X.126527 -
Frontiers in Pharmacology 2022Soft tissue sarcomas are a highly heterogenous group of tumors with limited systemic therapy options. Eribulin, a synthetic analogue of halichondrin B, is a potent... (Review)
Review
Soft tissue sarcomas are a highly heterogenous group of tumors with limited systemic therapy options. Eribulin, a synthetic analogue of halichondrin B, is a potent mitotic inhibitor. A phase 3 trial of previously treated advanced Liposarcoma and Leiomyosarcoma demonstrated superiority of eribulin to dacarbazine. Eribulin appears to be particularly effective for liposarcomas. It has also been shown to be a safe and effective treatment alternative to doxorubicin in patients where doxorubicin is contraindicated. From retrospective studies, eribulin has demonstrated efficacy in patients with angiosarcoma, pleomorphic sarcomas, synovial sarcomas, rhabdomyosarcomas, angiosarcomas, and myxofibrosarcomas. Future areas of development include liposomal eribulin, which may provide increased efficacy and lower toxicity, and delineation of biomarkers of response and resistance, allowing better selection of patients for treatment.
PubMed: 35444542
DOI: 10.3389/fphar.2022.869754