P.J.: *.- Eribulin No es Más Activo que la Dacarbazina en las Medidas Convencionales de Eficacia .
*.- Yondelis Aporta a los Pacientes un Beneficio Clinico Prolongado del 20 al 30 % .
*.- Yondelis ofrece una opción de tratamiento significativa para los pacientes con liposarcoma avanzado y leiomiosarcoma"
*.- Eribulin ha sido aprobado por la FDA tan solo para el tratamiento de Liposarcomas y ademas sus beneficios se obtienen en Tercera linea por lo que realmente beneficiara a muy pocos pacientes y el beneficio-riesgo-costo es más que dudable ... asi opina el Oncologo Ian Judson:
* Eribulin mejora la supervivencia ( OS ) en pacientes con liposarcoma en 2 Meses en comparacion con el Tratamiento Standar Dacarbazine .
* Sin embargo, no hubo diferencia en la supervivencia libre de progresión (PFS ) entre los dos grupos.
* El beneficio de supervivencia con eribulina se observó en los pacientes que se encontraban en su tercera línea de tratamiento del Liposarcoma.
* Sin embargo, "el aumento de la supervivencia observada con eribulin debe sopesarse frente a la carga de efectos secundarios que los pacientes experimentaron", comentó Gary K. Schwartz, MD, jefe de la División de Hematología y Oncología en la Universidad de Columbia Medical Center, en la Ciudad de Nueva York, que es un portavoz de ASCO.
* Eribulin es más tóxico que el dacarbazina, Señala el doctor Judson . Eventos adversos emergentes del tratamiento (TEAEs) fueron más frecuentes en los pacientes tratados con eribulina que en los tratados con dacarbazina. TEAEs incluido neutropenia (44% vs 24%), pirexia (28% vs 14%), neuropatía sensorial periférica (20% vs 4%), y la alopecia (35% vs 3%). También fueron más frecuentes TEAEs de grado 3 (63% vs 53%) y de grado 4 (26% vs 20%), así como TEAEs mortales (4% vs 1%), señalaron los investigadores.
* Dr. Judson concluye que eribulina no es más activo que la dacarbazina en las medidas convencionales de eficacia, como el porcentaje de respuestas o estabilización de la enfermedad, y que no tiene ningún efecto aparente sobre el control de enfermedades .
* Además Eribulin es mucho más caro. Eribulin cuesta $ 5511 por ciclo de tratamiento, mientras que el comparador y la terapia estándar, dacarbazina, cuesta $ 78 por ciclo. Así que hay un signo de interrogación sobre su rentabilidad, dijo.
* "¿Es asequible tratar a los pacientes con eribulin para un aumento de 2 meses en la supervivencia sin reducción de la carga tumoral, a pesar de una toxicidad significativa?" .
* "Sin reducción del tumor o de mejor calidad de vida, Eribulin tan sólo consigue un pequeño aumento en la supervivencia ... ¿ significativa ?" .
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Zosia Chustecka | January 28, 2016 .
Eribulin mesylate (Halaven, Eisai Inc.) has been approved by the US Food and Drug Administration (FDA) for use in the treatment of liposarcomas. This is the first drug to show an improvement in overall survival in this disease, the agency noted.
Eribulin is already approved for the treatment of advanced breast cancer. The new indication is for use in liposarcoma that is unresectable or advanced (metastatic) in patients who have received prior chemotherapy that contained an anthracycline drug.
Liposarcoma is a specific type of soft tissue sarcoma that affects fat cells and can form almost anywhere in the body, but is most common in the head, neck, arms, legs, trunk, and abdomen, the agency notes. An estimated 12,000 cases of soft tissue sarcomas were diagnosed in 2014 in the United States, according to the National Cancer Institute.
The improvement in overall survival for the first time in liposarcoma was reported last year by Medscape Medical News, when it was reported at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting at a session on soft tissue sarcomas.
At the meeting, the data presented came from a trial conducted in 452 patients with liposarcoma and leiomyosarcoma, which compared eribulin with standard therapy, dacarbazine (DTIC-Dome, Bayer HealthCare Pharmaceuticals). At the ASCO meeting, the results from 452 patients showed an improvement in survival of 2 months; the median overall survival was 13.5 months with eribulin vs 11.5 months with dacarbazine (hazard ratio, 0.768; P = .0169).
The FDA said that the data that led to approval were based on 143 patients with liposarcoma, and they show 7-month improvement in survival (15.6 months with eribulin compared with 8.4 months with dacarbazine), and the agency described this as "clinically meaningful."
However, when the results were presented at ASCO, there was no difference in progression-free survival between the two groups.
At the same session, another large phase 3 trial was presented, showing that trabectedin (Yondelis, PharmaMar) improved progression-free survival in patients with L-sarcomas, but not overall survival. These data on trabectedin led to its approval by the FDA in October 2015 for use in liposarcoma and leiomyosarcoma.
At the meeting, both trials were hailed as positive, and both have now resulted in approvals, and yet they have exactly opposite results ― eribulin improved overall survival but not progression-free survival, whereas trabectedin improved progression-free survival but not overall survival. Which end point is clinically more meaningful remains an important question, said the discussant for the presentations, Ian Robert Judson, MD, from the sarcoma unit at the Royal Marsden Cancer Hospital in London, United Kingdom.
Dr Judson noted that the results with eribulin in sarcoma, as presented at the ASCO meeting, follow the same pattern that was seen with this drug in breast cancer (in the pivotal EMBRACE trial), which also showed an improvement in overall survival of around 2 months, but also no improvement in progression-free survival.
This contrasts with what is usually seen with drugs active against cancer, he commented; usually they prolong progression-free survival and are also shown to improve overall survival. This is the opposite, and "we don't know quite what is going on here," he said, adding that it might be due to a different mechanism of action. Eribulin acts as an inhibitor of microtubule dynamics, and it may be affecting the tumor microenvironment, he suggested. "It does look like a true biological effect," he added.
However, eribulin was more toxic than dacarbazine, Dr Judson noted. Treatment-emergent adverse events (TEAEs) were more frequent in patients treated with eribulin than in those treated with dacarbazine. TEAEs included neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%), and alopecia (35% vs 3%). Also more frequent were TEAEs of grade 3 (63% vs 53%) and grade 4 (26% vs 20%), as well as fatal TEAEs (4% vs 1%), the researchers note.
Dr Judson commented that eribulin was not more active than dacarbazine on conventional measures of efficacy, such as percentage of responses or stable disease, and that it has no apparent effect on disease control. Previous studies have shown that effective chemotherapy improves pain and sleeplessness, but there appeared to be no effect on symptoms with eribulin.
In addition, it is very much more expensive. Eribulin costs $5511 per cycle of treatment, whereas the comparator and standard therapy, dacarbazine, costs $78 per cycle. So there is a question mark over its cost-effectiveness, he said.
In the FDA announcement of the approval, the agency noted that the most common adverse effects seen with eribulin were fatigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia. The drugs may also lead to neutropenia or decreased levels of potassium or calcium.
Neutropenia and neuropathy can be serious adverse effects, the agency noted, and added that the drug may be fetotoxic, and may lead to QTc prolongation, which could be fatal.
Eribulin had priority review and also received orphan drug designation for this indication, the FDA noted.