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Ritux 3rd phase CLL


22397 akademikeren 20/11 2009 19:08
Oversigt

LL: Phase III Studies Confirm Added Rituximab Better than Chemo Alone
Goodwin, Peter
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ASH Abstracts 325 and LBA-1

SAN FRANCISCO-For patients with chronic lymphocytic leukemia (CLL), two Phase III studies reported at the ASH Annual Meeting here showed improved rates of complete response and progression-free survival when rituximab (R) was added to standard fludarabine/cyclophosphamide (FC) chemotherapy.

Figure. MICHAEL HALL...
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The first, presented by Michael Hallek, MD, Chairman of the German CLL Study Group and Director of the Internal Medicine Clinic at the University of Cologne, randomized 817 physically fit, previously untreated patients with advanced CLL from 11 countries to receive six cycles-four weeks each-of either FC, or the same regimen plus rituximab (FCR). (The doses were: fludarabine at 25 mg/m2 iv d1-3 and cyclophosphamide at 250 mg/m2 iv d1-3 for both arms; and rituximab at 375 mg/m2 iv d0 at first cycle and 500 mg/m2 d1 for all subsequent cycles in the experimental arm.)The major endpoint was progression-free survival, which increased from 62% in the FC arm to 77% in the arm with rituximab. Dr. Hallek said that although the overall response rate increased only from an already high 88% to 95%, this gain was significant and that within it, the complete response rate nearly doubled, from 27% to 52%.
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Toxicity Increased

These gains, though, were bought at the price of increased toxicity, with severe hematologic toxicity up from 39% to 55% of patients in the immunochemotherapy arm. Neutropenia went up a third (from 21% to 34%) and leukocytopenia nearly doubled (from 12.1% to 24%) with both of these increases significant, but there was no increase in severe infections.Thrombocytopenia and anemia both improved somewhat in the group receiving rituximab-from 7% to 10%, and from 5% to 7%-and there was little change in treatment-related mortality.
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New Standard Front-Line

It is important to stress that patients with CLL are very often elderly, Dr. Hallek said in an interview. So one of the major things I should mention before coming to a conclusion is that we did this trial on physically fit patients, with selection based on a cumulative index rating scale and creatinine clearance. And in those physically fit CLL patients, I would now recommend an FCR regimen as a first-line treatment for CLL.
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Just 'a Little Bit' Impressed by the Study

Asked for this article how impressed he was by the study, George Canellos, MD, the William Rosenberg Chair and Professor of Medicine at Harvard Medical School and a senior physician in the Department of Hematologic Oncology at Dana-Farber Cancer Institute, replied: A little bit.

Figure. TADEUSZ ROBA...
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But he noted that there were a number of positive factors going for Dr. Hallek's study cohort, because patients appropriate for this protocol qualified by being fit; and the median age was 61-also fairly favorable: And so if you're fit and otherwise without serious comorbid illness, FCR does give you a better response rate, especially a better complete response rate, and a longer progression-free survival, Dr. Canellos said.
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Relapsed/Refractory

The second study of FCR vs FC-presented as a Late-Breaking Abstract-was in 552 patients from 17 countries who had relapsed or refractory chronic lymphocytic leukemia. The REACH (Rituximab + Chemotherapy in Relapsed/Refractory Chronic Lymphocytic Leukemia) trial reported an increase of 10 months in progression-free survival and a doubling of complete remission rates with an excellent safety profile.Study presenter Tadeusz Robak, MD, PhD, Chair of the Department of Haematology at Medical University of Lodz, Poland, noted that in both arms of the study patients received fludarabine (25 mg/m2 iv, day 1-3) with cyclophosphamide (250 mg/m2 iv, day 1-3) for six cycles of four weeks. Patients in the immunochemotherapy arm additionally received rituximab (375 mg/m2 d0 in the first cycle and 500 mg/m2 d1 in cycles 2-6).Patients of all Binet stages were included, and had received an average of one previous chemotherapy regimen per patient.
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Study Outcomes

Immunochemotherapy with FCR increased the overall response rate significantly (from 58% to nearly 70%) and nearly doubled the complete remission rate (from 13% to 24%), while prolonging progression-free survival time by a median of 10 months (from 20.6 to 30.6 months).Dr. Robak noted a slightly higher incidence of cytopenias in the FCR arm, with no difference in infection rates. On the basis of these two trials, we now have confirmation of our previous assumption that immunochemotherapy is better for CLL than chemotherapy alone; I believe it should be the new standard of therapy, he said.
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'Example of the Three 10s'

Asked for his perspective about the study, Dr. Canellos was less than enthusiastic: Well, I call it the results of 10s. The overall response rate is 10% greater, using FCR over FC. The CR rate is 10% greater, and the response lasts 10 months longer! So it really is an example of the three 10s.The glaring fact is that rituximab by itself, at conventional doses, is very inactive in CLL, he said, acknowledging, though, that when added to chemotherapy, rituximab does obviously produce an enhanced effect.But he noted: What isn't obvious here is that overall survival is still a matter of debate in this series-whether or not there is a difference in overall survival. The median was not reached for FCR, and was 53 months for FC.
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Three Drugs Better

The Chair of a news conference at which both CLL studies were discussed, Linda Burns, MD, Professor of Medicine and the Fellowship Director of the Hematology, Oncology, and Transplantation Division of the University of Minnesota, said afterwards, What this tells physicians is that the three-drug regimen is better than two drugs. But you still also need to look at the patient you have in front of you. And if you're concerned about that patient being weaker with underlying illnesses, two drugs still may be better.



20/11 2009 19:48 troldmanden 122398



Og her er en ny stor præsentation af CLL indikationen med både data fra Arzerra og Riruxan. En ren lækkerbisken for hardcore genmabber
hematology.wustl.edu/conferences/presentations/ansstas100209.ppt



21/11 2009 00:09 gentogen 022407



Jeg er lidt usikker på, hvad du vil sige med denne "nyhed", der jo er fra 10. februar 2009?

mvh



21/11 2009 00:12 gentogen 022408



Altså AKAs tekst...




21/11 2009 09:52 akademikeren 022415



Troldmanden slides er fra februar og mine forsøgsdata var bare dokumentation om den nyhed vi talte om igår og som jeg tror er ret vigtig. Det er hvorvidt Ritux er godkendt eller ej til CLL 1st line. FDA har givet dem et complete response i forgårs og i går i børsen kunne man læse de ikke var godkendt.



21/11 2009 11:08 Solsen 022420



http://www.news-medical.net/news/20091119/FDA-issues-..

Afventer godkendelse og får den sikkert i 1. line



21/11 2009 11:57 gentogen 022426



Tak for kommentarerne. Nu har jeg ikke set Børsens formuleringer, men sådan meget bogstaveligt talt, så er det jo rigtigt, at de ikke har fået godkendelsen, men det betyder jo bare IKKE, at de er blevet afvist, men at sagen ikke er endeligt afklaret. Den vej rundt er det vel svaht positivt (hvis man ser godkendelse som positivt), da de vel kunne være blevet afvist på nuværende tidspunkt. Så mon ikke Solsen har ret.



21/11 2009 11:30 CHjort 022423



gentogen, jeg er også lidt usikker på hvad AKA,s tekst skal bruges til.
Men måske dette????

Håb, Musk, og, GEN.CO




21/11 2009 12:08 gentogen 022427



Ja, jeg skal da gerne indrømme, at vi er nogle, der har det hårdt og godt kunne bruge dine handelskundskaber.

Hvis man ser på de fundamentale tilgængelige data om Genmabs produkter, så vurderer jeg det ikke desto mindre blot stadig sådan, at Genmab klart er inde i konkurrencen om de store penge. Gentagne studier viser, at Arzerra mindst er på niveau med milliardsælgeren. På den kommende konference dokumenteres det igen (og det er ikke mindst GDK folk, der har lavet analysen i øvrigt).

Men indrømmet igen: Det har godt nok været dyrt at være stærk i troen (selv om pointen som sagt er, at det jo ikke kun er en trossag).

Jeg har valgt fortsat at holde, men tager i øvrigt gerne imod gode råd, da det da lige pt. ser ud til, at alle andre er klogere end jeg er...

mvh og god weekend til jer alle sammen




21/11 2009 12:50 akademikeren 022430



Hej Gentogen,

Vi to og en del andre er nok i samme båd. Så det er ikke alle andre der er klogere end os. Vi er ihvertfald to.



21/11 2009 21:04 CHjort 222442



Humor, øhhhhh... en båd, en del og så jer to- "Så det er ikke alle andre der er klogere end os"



22/11 2009 00:22 gentogen 022446



Ja man mindes jo uvilkårligt den berømte sketch om de tre mænd på en tømmerflåde....eller var det to....

Men mon ikke også de patienter, som for eksempel har opnået en CR i Genmabs O-FC studium går rundt og smiler til verden og til Genmab. Om det så også er klogt at tænke på dem, skal jeg ikke kunne afgøre.

mvh





22/11 2009 11:27 akademikeren 022451



Netop Gentogen, et andet perspektiv er jo netop dette at vi som aktionærer har medvirket til at der er kommet et nyt kræftmiddel på markedet. Og man kan da går ind på CLL communitiet side og se hvad det betyder for de patienter, hvoraf nogle har aktivt kæmpet for at få Arzerra godkendt og sågar rejst kloden rundt for at få fat i det. Nu kan de få det via injektion i et onkologicenter tæt ved deres bolig.

At et firma kan lykkedes og kursen crasche er blot endnu en grund til at jeg - post genmab - aldrig nogensinde vil investere i Biotek igen. Det er ikke kun kontraintuitivt. Det gør egentligt at man ikke rigtigt kan bruge sin fundamental analyse til noget som helst. Så kan man ligeså godt til EFTER godkendelse og EFTER de første salgstal.

Hvis det er nogen trøst så er vi kun 3 måneder fra det.



22/11 2009 14:10 Sibelius 022456



Tror nu egentlig der er al mulig grund til at investere i biotek hvis der er en rimelig case - blot man følger en lidt mere aktiv strategi end "Buy and hold no matter what".

Hvis du havde haft en Genmab ramme de sidste 4 år hvor 50% har været køb og salg i op og nedture og de 50% har ligget fast i depotet tror jeg du kunne have tjent ret godt på dine Genmab.



22/11 2009 15:07 akademikeren 222457



Mit Vandloo har været at jeg mener at have kunnet analysere mig frem til at casen er blevet fundamental bedre og mere sikker med mindre risiko.

Markedet har så tolket sig frem til det præcist modsatte og nu også sekunderet af analytikerne.

At dette så ser ud som om og måske er forelskelse må jeg lære at leve med og jeg skal nok komme igen også på investeringsfronten. Men sjovt er det ikke. Og jeg må konstatere at jeg hælder mere og mere til Buffets credo... hvis jeg ikke kan forstå produktet vil jeg ikke nvestere i det.

De seneste måneders analyse af Arzerra´s potentiale har udviklet sig til raketvidenskab. En raketvidenskab der er så kompliceret at Jyske kan vende på en tallerken og pludselig på et halvt år kører kursmålet ned fra +300 til 70.

Det er ikke investering, det er ikke analyse. Det er noget andet. Og det kan man ikke sætte sine penge efter.

Just my 2 cents...that started with a million



22/11 2009 17:29 fillipa1 022460



Hej Aka.

jeg kan meget nemt følge din tanke gang...sidder også tilbage med en mærkelig fornemmelse af at jeg måske ikke har kune se skoven for bare træer(forelsket) synes som dig kun casen er blevet bedre...men står nu ved en skillevej skal jeg sælge alt og holde fingrene væk fra biotek fremover, gør jeg nok alligevel, eller skal jeg vente på et stemningsskift...
Har nogen en ide om hvornår vi kan forvente resulstater fra de andre fase3 af azerra.. input velkmne...jeg kan desværre ikke bidrage med noget nyt eller positivt pt.
Kunne selvfølgelig være rart med et takeover men tror ikke selv på det på nuværende tidspunkt...
God aften

Fillipa





22/11 2009 18:26 CHjort 022462



Nå, men for at det hele ikke skal blive alt for surt med de Gen-mab?ber får I lige en video fra seneste presse/analytiker seance. Bemærk at pipeline viser klare tegn på liv og aktivitet. Fru Direktør Lisa D. besidder ikke kun evnen til at gå på vandet, men bevæger sig ligeså yndefuldt under vandoverfladen. Og er det ikke en perle vi ser?.. håbet er lysegrønt eller idet mindste rosa

Himlen kan ikke vente!



22/11 2009 19:49 gentogen 022470



Ja, der er da ikke noget at sige til, at vi er forelskede.
Og det er jo ikke fordi, der ikke sker noget:

Pipeline fase III ser ifølge Clinical Trials således ud:

Found 7 studies with search of: ofatumumab | Phase III
Hide studies that are not seeking new volunteers.
Display Options Rank Status Study
1 Not yet recruiting Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma Condition: Lymphoma, Large-Cell, Diffuse
Interventions: Drug: RITUXIMAB + DHAP; Drug: RITUXIMAB + DVD; Drug: OFATUMUMAB + DVD; Drug: OFATUMUMAB + DHAP

2 Active, not recruiting Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to MTX Therapy Conditions: Arthritis, Rheumatoid; Rheumatoid Arthritis
Interventions: Drug: Ofatumumab; Drug: Placebo

3 Recruiting Investigating Clinical Efficacy of Ofatumumab in Adult RA Patients Who Had an Inadequate Response to TNF-? Antagonist Therapy Conditions: Arthritis, Rheumatoid; Rheumatoid Arthritis
Interventions: Drug: Ofatumumab; Drug: Placebo

4 Recruiting Ofatumumab + Chlorambucil vs. Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia Condition: Chronic Lymphocytic Leukemia
Interventions: Drug: ofatumumab (GSK1841157) infusion; Drug: chlorambucil, tablets

5 Active, not recruiting HuMax-CD20 in Follicular Lymphoma (FL) Patients Refractory to Rituximab Condition: Follicular Lymphoma
Intervention: Drug: Ofatumumab-HuMax-CD20

6 Recruiting Ofatumumab Added to Fludarabine-Cyclophosphamide vs. Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia Condition: Chronic Lymphocytic Leukemia
Interventions: Drug: OFC Infusion; Drug: FC infusion

7 Active, not recruiting HuMax-CD20 in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Failing Fludarabine and Alemtuzumab Condition: B-Cell Chronic Lymphocytic Leukemia
Intervention: Drug: ofatumumab

+ en masse i fase I og II




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