16 december 2016: Bron: Fase III CREATE-X clinical

Capecitabine - Xeloda aanvullend op chemo of hormoontherapie post operatief bij vrouwen die ondanks neo adjuvante chemo (chemo voordat de operatie plaatsvindt) toch nog actieve tumorcellen hebben in weggehaald tumorweefsel en/of lymfklieren geeft 31% minder kans op een recidief op 2-jaars meting in vergelijking met placebo aanvullend op chemo of hormoontherapie. 

Alle aan de studie deelnemende borstkankerpatiënten (totaal 910 patiënten) hadden HER2 negatieve borstkanker en actieve tumorcellen in weggehaald tumorweefsel en/of lymfklieren.


Belangrijkste resultaten:
  • De onderzoekers vonden dat 2 jaar na de studie de patiënten uit de capecitabine/xelodagroep 31% minder kans op een recidief hadden dan de patiënten die een placebo hadden gekregen.
  • Ziektevrije overleving op 2 jaar was 87.3% voor patiënten uit de capecitabine - Xeloda groep en 80.5% voor de plaecbogroep. .
  • Na twee jaar was er een tendens voor een betere overall overleving voor de capecitabine/xelodagroep in vergelijking met de placebogroep: mediane overall overleving op 2 jaars meting was 96.2% versus 93.9%. Deze data zijn nog definitief maar kunnen eigenlijk alleen maar beter worden naarmate de follow-up van de studie langer duurt, aldus de onderzoekers.
  • Volgens de onderzoekers geeft capecitabine - xeloda minder bijwerkingen en zijn deze bijwerkingen gemakkelijker te controleren dan chemo via infuus.

Dit zijn de eerste resultaten na twee jaar follow-up van de Japanse gerandomiseerde fase III studie CREATE X. In de studie werden de 910 deelnemers gerandomiseerd ingedeeld in twee groepen van ieder 455 patiënten.

Het volledige studierapport: 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)

is nog niet voorhanden maar hier het abstract zoals dat op het borstkankercongres in San Antonio afgelopen week werd gepresenteerd

Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy

Source: San Antonio breast cancer congres 2015

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)

Toi M, Lee S-J, Lee ES, Ohtani S, Im Y-H, Im S-A, Park B-W, Kim S-B, Yanagita Y, Takao S, Ohno S, Aogi K, Iwata H, Kim A, Sasano H, Yokota I, Ohashi Y, Masuda N. Yeungnam University Hospital, Daegu, Korea; Kyoto University Hospital, Kyoto, Japan; National Cancer Center, Seoul, Korea; Hiroshima City Hospital, Hiroshima City, Hiroshima, Japan; Samsung Medical Center, Seoul, Korea; Seoul National University Hospital, Seoul, Korea; Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Asan Medical Center, Seoul, Korea; Gunma Prefectural Cancer Center, Ota, Gunma, Japan; Hyogo Cancer Center, Akashi, Hyogo, Japan; National Kyusyu Cancer Center, Fukuoka, Japan; NHO Shikoku Cancer Center, Matsuyama, Ehime, Japan; Aichi Cancer Center, Nagoya, Aichi, Japan; Korea University Guro Hospital, Seoul, Korea; Tohoku University, Sendai, Miyagi, Japan; Kyoto Prefectural University of Medicine, Kyoto, Japan; Chuo University, Tokyo, Japan; NHO Osaka National Hospital, Osaka, Japan

Key Points:
  • Researchers found that, 2 years after starting the study, patients who were assigned to capecitabine had a 31% reduced risk of disease recurrence compared with those assigned to placebo.
  • Disease-free survival was 87.3% for those assigned to capecitabine, and 80.5% for those assigned to placebo.
  • There was a nonsignificant tendency toward improved overall survival for those assigned to capecitabine; 2-year median overall survival was 96.2% vs 93.9%. These data are not yet mature, and it is possible that overall survival differences will become more pronounced as more time elapses.

Patients (pts) with pathologic residual invasive disease after neoadjuvant chemotherapy (NAC) have an intermediate or high-risk for relapse. It is not clear whether further systemic chemotherapy is beneficial for these pts. CREATE-X is a multicenter open-label randomized phase III trial evaluating this major clinical issue using capecitabine (X) in pts without pCR after NAC (UMIN000000843). We have shown previously that the addition of 8 cycles of X to standard adjuvant therapy is feasible and well tolerated (Ohtani S, et al. SABCS2013#P3-12-03). We report the first efficacy results from a pre-planned interim analysis after 2-year follow-up.

Pts with HER2-negative residual invasive cancer after anthracycline- and/or taxane-containing NAC were randomized to standard treatment (RT, hormone therapy (HT) as appropriate) with or without 8 cycles of X (1250 mg/m2 bid, days1–14,q3w). Pts with hormone receptor (HR)-positive disease received HT either with or after X, according to each center's prespecified standard practice. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS), safety, and cost-effectiveness. It was originally planned to enroll 450 pts in each arm in order to detect a HR 0.74 improvement in the X arm with 80% power and a two-sided 5% significance level. We planned one interim analysis of DFS at 2-years after all pts enrolled using Lan-DeMets alpha spending function method (O'Brein-Fleming type).

Between Feb 2007 and Jul 2012, 910 pts were randomized, with 455 pts to receive X. The full analysis consisted of 902 pts who matched the inclusion criteria. Baseline characteristics were well balanced. The median age was 48 years in both arms; 63.5% were HR-positive. In the investigational arm, HT was given with X concurrently in 200 pts and after X in 24 pts. The relative dose intensity of X was 78.8%. At the time of the interim analysis, DFS events were confirmed in 81 (18.8%) in the investigational arm and 109 (24.7%) in the standard arm, and OS events were 28 (6.5%) and 41 (9.3%), respectively. On Kaplan-Meier analysis, 2-year DFS was 87.3% for the arm with X and 80.5% for no X (HR:0.688, 98.66%CI: 0.479-0.989, log-rank P=0.001). The tendency for improvement of OS by adding X was also confirmed; 2-year OS was 96.2% and 93.9%, respectively (HR: 0.658, 95%CI: 0.407-1.065, log-rank P=0.086). In the experimental arm with X, grade 3/4 toxicities included HFS (11%), neutropenia (9%), diarrhea (3%), and fatigue (1%); all were controllable. No SAE was related to X administration. Because the study met the primary endpoint, an independent data monitoring committee recommended discontinuation of the study.

The clinical utility of X in the adjuvant setting for breast cancer pts has been proven to improve the prognosis based on the pathological response-guided strategy. Tolerability was consistent with the established safety profile of X in mBC. The benefit to risk balance of the addition of 8 cycles of X 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.

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