Capecitabine Improves HER2-Negative Breast Cancer Survival After Post-Op Residual Disease

Capecitabine Improves HER2-Negative Breast Cancer Survival After Post-Op Residual Disease
HER2-negative patients who do not have a complete pathological response after neoadjuvant chemotherapy and surgery may benefit from adjuvant capecitabine

Date: 10 Dec 2015
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Anti-Cancer Agents & Biologic Therapy / Breast Cancer, Early Stage

medwireNews: Treatment with capecitabine significantly improves survival for HER2-negative breast cancer patients who have residual disease after neoadjuvant chemotherapy and surgery, phase III trial results suggest.

The CREATE-X study was discontinued after the planned interim analysis demonstrated that the addition of the 5-fluorouracil prodrug to postoperative chemotherapy met the primary endpoint of significantly improved disease-free survival compared with no capecitabine.

The 2-year rate of disease-free survival was 87.3 versus 80.5% with a hazard ratio [HR] of 0.688, reported Masakazu Toi, from Kyoto University Hospital in Japan and director of the Japan Breast Cancer Research Group, and co-authors at the San Antonio Breast Cancer Symposium in Texas, USA.

Overall survival was also significantly improved with capecitabine treatment, with 2-year rates of 96.2% versus 93.9% for no capecitabine, and a HR of 0.658.

The study included 902 HER2-negative patients who were randomly assigned to receive hormone therapy where appropriate and either eight cycles of capecitabine, at a twice-daily dose of 1250 mg/m2 for 2 weeks followed by 1 week off treatment, or no additional chemotherapy.

Grade 3 or 4 adverse events reported in the capecitabine arm of the study included hand–foot syndrome (11%), neutropenia (9%), diarrhoea (3%) and fatigue (1%) but all symptoms were described by the researchers as “controllable”.

Masakazu Toi commented on the results in a press release: “These data are exciting, because the side effects of the treatment were manageable and the benefit of capecitabine treatment was clear.”

The authors conclude: “The benefit to risk balance of the addition of 8 cycles of [capecitabine] to standard adjuvant therapy seems to be satisfied. This evidence might allow the development of personalized individualized treatment based on the response to primary systemic therapy.”

Reference

Toi M, Lee S-J, Lee ES, et al. Abstract S1-07. A phase III trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04). Reported atSan Antonio Breast Cancer Symposium; San Antonio, Texas, USA: 8–12 December 2015.

Los Avances en Cáncer Gástrico SEOM

Los Avances en Cáncer Gástrico
Miércoles, 09 de Diciembre de 2015 14:35

El cáncer gástrico es un problema sanitario de primer orden. Hoy en día representa la 5ª causa de muerte por cáncer en el hombre y la 6ª en la mujer, con más de 56.000 fallecimientos anuales en Europa. En las últimas décadas se ha producido una disminución en su incidencia en países occidentales aunque con un incremento relativo en la frecuencia de los adenocarcinomas localizados en el cardias y la unión esofagogástrica.

Los pacientes que debutan con estadios precoces se tratan con cirugía curativa y suelen recibir quimioterapia perioperatoria o bien quimiorradioterapia adyuvante. Sin embargo, muchos de ellos recaen, de modo que la proporción de largos supervivientes no supera el 25%. Cuando la enfermedad se detecta en estadio localmente avanzado o metastásico (lo que ocurre en dos terceras partes), el pronóstico es desfavorable, con medianas de supervivencia en torno a los 12 meses. El objetivo del tratamiento en este contexto es principalmente paliativo.

Pero en las últimas décadas hemos asistido a notables avances en el tratamiento de esta enfermedad que han permitido mejorar el pronóstico en todos los estadios y vislumbrar un aumento de la supervivencia en el futuro:

- En los años ´90 se demostró que la quimioterapia mejoraba la supervivencia y calidad de vida en pacientes con enfermedad metastásica (en comparación con el tratamiento sintomático exclusivo).
- A principios del año 2000, por medio de metaanálisis de estudios aleatorizados, se confirmó que la poliquimioterapia es superior al empleo de agentes únicos en términos de respuestas y supervivencia, a expensas de un aumento de la toxicidad.
- El esquema de referencia desde entonces es la combinación de cisplatino y 5-fluorouracilo en infusión continua.
- Estudios posteriores han demostrado que ambos fármacos pueden ser sustituidos por agentes menos tóxicos, oxaliplatino y capecitabina, respectivamente (2008).
- Los tripletes con docetaxel o epirrubicina (DCF, EOX) son superiores a los dobletes en pacientes seleccionados sin comorbilidades (2006).
- La quimiorradioterapia adyuvante (5FU-LV en esquema de Macdonald, 2001) y la quimioterapia perioperatoria (ECF en esquema MAGIC, 2006) reducen el riesgo de recidiva y mejoran la supervivencia tras la resección quirúrgica en estadios localizados.
- La adición de trastuzumab (primer anticuerpo monoclonal aprobado en esta patología) en pacientes con sobreexpresión de HER2 (HER2+++ o FISH+) mejora significativamente los resultados de la quimioterapia (cisplatino y fluoropirimidinas) en enfermedad avanzada. Por ello, debe determinarse la sobreexpresión de HER2 en todos los pacientes con cáncer gástrico avanzado (2010).
- La quimioterapia de segunda línea (con taxanos o irinotecán) es activa y mejora la supervivencia en pacientes seleccionados (2011).
- Ramucirumab es un fármaco antiangiogénico (antagonista del VEGFR-2) que se ha aprobado recientemente en esta enfermedad. Cuando se emplea sólo o asociado a la quimioterapia (paclitaxel) aumenta la supervivencia en el tratamiento de segunda línea (2014).

NHS England and NICE plans to reform Cancer Drugs Fund

NHS England and NICE Have Begun a Consultation on a New Cancer Drugs Fund
Consultation now open on plans to reform Cancer Drugs Fund

Date: 01 Dec 2015
Topic: Bioethics, legal and economic issues

NICE announced on 19 November 2015 that a 12-week consultation has started on draft proposals outlining new arrangements for the Cancer Drugs Fund (CDF). It will enable patients to receive new treatments that can't yet be recommended for routine use but which have genuine promise, while real world evidence is collected for up to two years on how well the drugs work in practice.

The proposals are aimed at providing patients with access to promising new medicines while the evidence is still emerging, in a financially sustainable way.

They are intended to create a system that captures data and information on new medicines and other technologies to develop a more robust evidence base.

The proposal is that the CDF will become a ‘managed access’ fund for new cancer drugs to give early access to those drugs which appear promising but which have currently uncertain evidence bases which are insufficient to support a recommendation for routine commissioning. The new scheme would operate from April 2016.

All new cancer drugs will normally receive a clear ‘yes’ (baseline commissioning), ‘maybe’ (CDF funding for time limited period), or ‘no’ funding decision within 90 days of market authorisation.

The new CDF will collect important information on longer-term benefits which may not be available at the time of licensing, as the chief executive of NICE, Sir Andrew Dillon, explained:

“Our joint proposals will ensure that the Cancer Drugs Fund is used to provide patients with promising medicines at a cost which reflects the uncertainty about their effectiveness and cost effectiveness and at the same time, generate additional data to help the NHS make a longer term decision on whether and how to use them.”

Simon Stevens, Chief Executive of NHS England, said: “Over the next five years we're likely to see many new cancer drugs coming on to the worldwide market - some of which will be major therapeutic breakthroughs, and some of which will turn out to offer little extra patient benefit but at enormous cost.

"The new Cancer Drugs Fund offers a route for sorting out the wheat from the chaff, so that patients in England get faster access to the genuinely most promising new treatments. For those drug companies willing to price their products affordably while sharing transparent information about 'real world' patient benefit, the new CDF will offer a new fast-track route to NHS funding.”

The original CDF was established in 2011 to fund cancer drugs in England that are not currently approved by NICE. The current CDF runs until April 2016.

The proposal issued on 19 November for public consultation outlines a new system, fully integrated into the NICE appraisal process, where the CDF becomes a transitional fund – with clear criteria for entry and exit.

This is in line with the recommendation of the recently published independent Cancer Taskforce report, which proposed that the new CDF should operate with NHS England and NICE.

It’s proposed that from April 2016, all new cancer drugs will be referred to NICE for appraisal. Cancer drugs would normally receive draft guidance from NICE before market authorisation, and final guidance normally within 90 days of market authorisation being granted.

The outcome of each initial NICE appraisal will be a recommendation falling into one of the following three categories:

Recommended for routine use
Not recommended for routine use
Recommended for use within the CDF

At the end of the period for use within the CDF, the drug will go through a short NICE appraisal, using the additional evidence.

The drug will then attract either a NICE positive recommendation, at which point it would move out of the CDF into routine commissioning. Alternatively, it will receive a NICE negative recommendation, meaning it would move out of the CDF and become available only on the basis of individual patient funding requests.

The consultation will run for 12 weeks until 11 February 2016.