7 januari 2011: onderaan staat nieuwe artikel over resultaten uit recente overzichtstudie van alle bekende gerandomiseerde fase II en fase III studies die de resultaten uit onderstaande studie van oktober 2010  bevestigen.

21 oktober 2010: Bron: Persbericht van Merck Serono

Erbitux geeft zelfde overlevingskansen en overlevingstijd als chemotherapie indien geven als monotherapie of in combinatie met chemo bij darmkankerpatienten met  het wild-type KRAS. De ziektevrije tijd verbeterde wel significant bij deze patienten. Hier het persbericht van Merck Senoro dat we ongewijzigd plaatsen met abstract erbij:

Early Tumor Shrinkage with 1st Line Erbitux Therapy Leads to Longest-Ever Median Survival in KRAS Wild-Type mCR

  • Further analysis of the CRYSTALa trial shows unprecedented median overall survival of 28.3 months for patients who experienced early tumor shrinkage
  • This finding further demonstrates the value of Erbitux as the first-choice, 1st line therapy

 

Milan/Darmstadt, Germany, October 10, 2010 – Merck Serono, a division of Merck KGaA, Darmstadt, Germany has announced that new data presented today at the 35th Congress of the European Society for Medical Oncology (ESMO) have shown that patients with KRAS wild-type metastatic colorectal cancer (mCRC) who experienced early tumor shrinkage (within 8 weeks) during 1st line Erbitux® (cetuximab) based treatment lived a median of 28.3 months.[i] Such a correlation between early tumor shrinkage and long-term survival was not observed in the chemotherapy-alone arm, in which survival did not exceed 21 months.

 

“These new data indicate that early tumor shrinkage with personalized Erbitux therapy correlates with significantly improved survival,” said study author Professor Eric Van Cutsem, Professor of Medicine and Digestive Oncology from the University Hospital Gasthuisberg in Leuven, Belgium. “Tumor shrinkage is important for providing symptom relief and vital for increasing the potential for curative surgery. These new findings go a step further in suggesting that early tumor shrinkage may also be an indicator for extended survival for patients treated with an Erbitux-based therapy.”

 

The Phase III CRYSTAL trial has previously demonstrated that mCRC patients with KRAS wild-type tumors treated with Erbitux achieved a median survival of 23.5 months. The new findings, derived from further analysis of the trial data, have shown that patients who experienced early tumor shrinkage with Erbitux-based treatment lived a median of 28.3 months.1 Early tumor shrinkage was defined as a 20% or greater tumor reduction within 8 weeks.

 

“Erbitux-based treatments have consistently achieved meaningful tumor shrinkage. The correlation between early tumor shrinkage and long-term survival seems to be Erbitux-specific as it has not been reported with any other mCRC therapies,” said Dr. Wolfgang Wein, Executive Vice President for Oncology at Merck Serono. “These data have the potential to establish Erbitux as the first-choice, 1st line therapy for all mCRC patients with KRAS wild-type tumors.”



[i] Piessevaux H, et al. ESMO Congress 2010. Abstract No: 596P.

Van Cutsem E, et al.. ASCO GI Congress 2010. Abstract No: 281.

EGRF remmers zoals Erbitux - Cetuximab en Panitimumab zijn alleen werkzaam bij darmkanker met tumoren met wild type van KRAS gen blijkt uit overzichtstudie van gerandomiseerde studies

7 januari 2011: Bro: Ann Intern Med. 2011 Jan 4;154(1):37-49.

Een grote overzichtstudie van alle zover bekende gerandomiseerde fase II en fase III studies bevestigen de reaultaten uit bovenstaande studie. Erbitux en Panitimumab zijn alleen efectief en werkzaam bij darmkanker met tumoren van het KRAS wild type. Voor alle andere tumoren met een ander KRAS gen werken deze middelen juist tegengesteld. Het lijkt dus superbelangrijk om vooraf aan uw behandeling van darmkanker het KRAS type te laten vaststellen. Hieronder het abstract van de overzichtstudie. Als u hier klikt kunt u een artikel in Medscape over deze bevindingen lezen.

Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer

  1. Issa J. Dahabreh, MD;
  2. Teruhiko Terasawa, MD, PhD;
  3. Peter J. Castaldi, MD, MS; and
  4. Thomas A. Trikalinos, MD

+ Author Affiliations

  1. From Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, and Nanakuri Sanatorium, Fujita Health University School of Medicine, Tsu, Japan.

Abstract

Background: KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti–epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab.

Purpose: To summarize whether KRAS mutation status modifies effects of anti-EGFR–based treatments for patients with advanced colorectal cancer and whether KRAS status predicts clinical outcomes among such patients.

Data Sources: MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language.

Study Selection: Three reviewers screened titles and abstracts to identify published studies assessing KRAS mutations as predictors of overall and progression-free survival or treatment failure for patients who received anti-EGFR–based therapy for metastatic colorectal cancer.

Data Extraction: Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies.

Data Synthesis: In 4 reanalyses of randomized trials of anti-EGFR–based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti-EGFR–based treatment among KRAS-positive patients (hazard ratio , 1.0). However, evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type patients. The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97).

Limitations: Limited evidence from randomized studies exists. Patient-level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern.

Conclusion: KRAS mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among patients with advanced colorectal cancer treated with anti-EGFR antibodies.

Primary Funding Source: Agency for Healthcare Research and Quality.

 


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