d.d. 22 september 2003: vervolginformatie over Avastin bij darmkanker.

Roche Holding meldt vandaag 22 september 2003 op de beurs (DOW) dat een Fase III studie bij 900 patiënten met uitgezaaide darmkanker een significant positief resultaat heeft gegeven voor het gebruik van Avastin in combinatie met de standaard chemokuren bij darmkanker. Al eerder hebben wij de studieresultaten van een fase II studie gemeld en al eerder ook kwamen de resultaten van deze fase III studie naar buiten, zoals u in het artikel hieronder kunt lezen. Avastin is een angiogeneseremmer, het blokkeert de bloedtoevoer naar de kankercellen zoals bv. ook methylglyoxal (zie ook verhaal van meneer B.) lijkt te doen. Als het waar is dat Avastin dit doet vragen we ons wel af waarom het verschil in gemiddelde overlevingstijd oplopend van 'slechts' 15.6 maanden naar 20.3 maanden niet veel langer is. Als het waar is dat Avastin de bloedtoevoer naar de kankercellen afsluit dan zou de logische gevolgtrekking o.i. moeten zijn dat ALLE kankercellen binnen een bepaald tijdsbestek gewoon afsterven. Maar blijkbaar groeien de kankercellen toch nog bij een aantal patiënten en worden patiënten toch weer resistent tegen ook Avastin?. Nu zijn wij geen arts of medisch deskundige dus is misschien onze overweging hier pure onzin. Maar we zouden graag eens van een oncoloog, liefst darmkankerspecialist horen hoe het dan werkelijk zit. We zullen ook een woordvoerder bij Roche hier eens naar vragen.
Overigens kregen we recent van twee bezoekers van de site het bericht dat zij hadden geprobeerd in Amerika informatie te krijgen over trials met Avastin bij longkanker, maar beide personen kregen te horen dat er geen trials met longkanker op dit moment lopen. Terwijl in dit bericht wel melding wordt gemaakt van lopende trials met Avastin bij alvleesklierkanker, longkanker en nierkanker. We vinden dit wel vreemd. Ook kennen we verschillende mensen met uitgezaaide darmkanker die met alleen dieet en extra suppletie, al of niet als aanvulling bij reguliere therapiën en bepaalde levensstijl hun overlevingstijd verdubbelen of zelfs nog meer tegenover de prognoses. Zie ook ervaringsverhalen van kankerpatiënten onder uw verhaal.

Of deze publicatie nu wel de weg vrijmaakt voor grootschalig gebruik van Avastin durven we dus niet te zeggen. Lees het persbericht van de DOW en daaronder het persbericht over de fase III trial van de website van Genentech, producent van Avastin.


-- Roche: Phase III Trials Show Avastin Improves Suvival --

Edited Press Release

LONDON -(Dow Jones)- Roche Holding said Monday that treatment with Avastin
(bevacizumab, rhuMAb-VEGF) - a new agent designed specifically to restrict the
blood supply to tumours - can significantly improve survival in advanced
colorectal cancer compared to established chemotherapy alone, according to data
presented at the European Cancer Conference (ECCO).
These results, from a 900-patient randomised Phase III study, showed that
Avastin increased survival duration by over 30% when combined with first-line
chemotherapy (IFL1) for advanced (metastatic) colorectal cancer.
In addition to the 30% survival rate, the study found that when Avastin was
added to IFL, patient survival time was extended from 15.6 months with
chemotherapy alone to 20.3 months. The time to disease progression, response
rate and duration of response were also all improved by Avastin, Roche said.
These clinical benefits were seen across all relevant patient subgroups in the
population, the data shows.
The combination of Avastin and chemotherapy was well tolerated, with only
grade 3 hypertension (> 180mmHg / > 110mmHg, which was manageable using standard
oral medication) clearly more frequent in the Avastin-containing arm of the
trial. Avastin is also under investigation in other forms of metastatic
cancer, including non-small cell lung cancer, pancreatic and renal cell
carcinoma.
An application for approval of Avastin in treating colorectal cancer will be
made to the European Union regulatory authorities in the coming months.

Phase III study of Avastin™ (bevacizumab, rhuMAb-VEGF) plus chemotherapy in previously untreated metastatic colorectal cancer patients met its primary endpoint. It improved overall survival. The magnitude of the benefit observed far exceeded what the study was designed to demonstrate. The trial also met the secondary endpoints of progressionfree survival, response rate, and duration of response. Genentech plans to submit data from this Phase III metastatic colorectal cancer trial to the annual meeting of the American Society of Clinical Oncology (ASCO), May 31 - June 3. This is good news, especially about a drug that analysts were skeptical about its promises and critics took advantage to underrate the stock because of it. Avastin is an antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays a critical role in tumor angiogenesis (the formation of new blood vessels to the tumor). By inhibiting VEGF, Avastin is designed to interfere with processes that are critical to tumor growth and metastasis. According to Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president Development and Product Operations, and chief medical officer, the data strongly suggest that inhibiting VEGF -- a growth factor first cloned by Genentech scientists -- results in clinical benefit for colorectal cancer patients and has the potential to change the practice of treating cancer. The study also provides the first Phase III clinical validation of the longpursued 'anti-angiogenic' hypothesis -- that by targeting a tumor's blood supply, you may impact its viability. Based on the strength of these data, Genentech plans to discuss the filing of a Biologics License Application with the U.S. Food and Drug Administration," continued Dr. Hellmann. * This multi-center study enrolled more than 900 patients, and randomized 800 patients to receive either Avastin plus the standard of care chemotherapy (5-FU/Leucovorin/CPT-11, called the Saltz regimen) or the Saltz regimen plus an Avastin placebo. A third arm of the study treated 100 patients with Avastin plus 5-FU/Leucovorin chemotherapy. This arm was dropped, as pre-specified, once safety with the Saltz regimen was established. 

Adverse Events 
The addition of Avastin to chemotherapy was well tolerated. While bleeding, thrombosis, asymptomatic proteinuria and hypertension were identified in Phase II studies as possible safety events, only Grade 3 hypertension, easily managed with oral medications, was clearly increased in this Phase III study. Gastrointestinal perforation, although uncommon, may be increased by the addition of Avastin to chemotherapy. Based on preclinical and clinical studies showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a late stage clinical development program with Avastin evaluating its potential use in metastatic colorectal, renal cell (kidney), breast and non-small cell lung cancers. To date, more than 2,000 patients have been treated with Avastin in clinical studies. Results from a second Genentech study in metastatic colorectal cancer are expected later this year. In October 2001, a Phase II study with Avastin in metastatic renal cell carcinoma conducted by the National Cancer Institute (NCI) was stopped early after reaching its pre-specified efficacy endpoint. Results from this study were presented at last year's ASCO meeting. Based on the positive data observed in this trial, two Phase III trials in metastatic kidney cancer are scheduled to begin enrollment this year. In addition, Phase III Eastern Cooperative Oncology Group (ECOG) studies continue to evaluate Avastin in second-line metastatic colorectal, first-line metastatic non-small cell lung, and first-line metastatic breast cancer. Additional studies are ongoing through the NCI in more than 20 different tumor types. 

Comments: 

Investors were led to believe that Avastin’s side effects would cause problem towards Avastin approval. The above-mentioned news might change this feeling, as the rewards seem to exceed, by far, the risk of side effects. This is definitely good news for Genentech, whose drug Xolar was recommended approval by the FDA advisory Committee.