Estos Resultados Obtenidos en Fase Ib vienen a Confirmar que "" PM01183 Iniciara Directamente la Fase III de Registro en Pacientes con Cáncer de Pulmón de Celulas Pequeñas ( SCLC ) "" un Estudio Pivotal de Fase III que Comparará la Combinación en segunda línea contra Topotecán, el único Medicamento Aprobado en EE. UU. y Europa para esta Indicación que existe an la actualidad .****************************************************************
Journal Oncology News | June 10, 2015 | ASCO 2015, Lung Cancer . By Cancer Network Staff .
Transcriptional Inhibitor With Doxorubicin Shows Promise in SCLC .
Results from a phase I study showed that transcriptional inhibitor PM01183 along with doxorubicin induced responses as a second-line treatment for patients with small-cell lung cancer (SCLC). The study (abstract 7509) was presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
PM01183 (Lurbinectedin) inhibits transactivated transcription by targeting RNA polymerase II. It also impairs the DNA repair system known as nucleotide excision repair (NER). In vitro research has shown that it acts synergistically with doxorubicin. In this phase I trial, 21 patients who failed one chemotherapy-containing prior line of therapy received a combination of PM01183 and doxorubicin. The median age of the patients in the trial was 62 years, and 76% of patients were male; 29% had brain metastases, and 62% had bulky disease.
The confirmed response rate in the trial was 67%, including approximately 10% complete responses. The median chemotherapy-free interval (CTFI) upon entering the trial was 3.1 months, and 48% of patients were considered resistant to prior therapy. The study found that CTFI was predictive of response (P = .001), with all sensitive patients responding to the treatment and 30% of resistant patients responding. The median progression-free survival was 4.6 months.
Grade 4 neutropenia was common, occurring in 86% of patients; grade 4 thrombocytopenia occurred in 19%, and grade 4 anemia occurred in 5%. Grade 3/4 febrile neutropenia was seen in 29% of patients, while other toxicities including fatigue, anorexia, and nausea/vomiting were generally mild. Three patients did discontinue the study drug because of toxicity, and five patients (24%) are still ongoing. There were no drug-related deaths.
“The rate, depth, and length of responses that we have observed with this treatment in the second-line setting are remarkable, even in those patients that are usually considered harder to treat,” said Martin Forster, MD, PhD, of University College Hospital in London, who led the study, in a press release. “Small-cell lung cancer is an unmet clinical need with very few recent advances and the scientific community is committed to help develop new effective therapies.”
PM01183 is being evaluated in a number of malignancies, including metastatic breast cancer, various types of leukemia, and non–small-cell lung cancer.