RESUMEN
PURPOSE: A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS: In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS: Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION: Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Genes BRCA1 , Genes BRCA2 , Mutación de Línea Germinal , Neoplasias Ováricas/tratamiento farmacológico , Ftalazinas/uso terapéutico , Piperazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Compuestos de Platino/uso terapéuticoRESUMEN
Squamous-cell carcinoma of the head and neck (SCCHN) is an important problem in Brazil, where epidemiological and socioeconomic features often create barriers to the implementation of combined modalities with curative potential. Cisplatin improves the efficacy of radiotherapy in the adjuvant treatment of localized SCCHN and in the definitive therapy of locally advanced disease. However, the addition of high-dose cisplatin to radiotherapy increases treatment toxicity and is not always warranted. A panel of experts convened in Sao Paulo, Brazil, for discussions and recommendations regarding the use of high-dose cisplatin in combination with radiotherapy in SCCHN. In addition to discussing their professional experience, panel members used the current literature to provide evidence-based, practical recommendations regarding sociodemographic or medical criteria that may preclude safe administration of cisplatin. It is hoped that the application of these recommendations in clinical practice may improve therapeutic results in Brazil and other countries with similar health-care environments.