Alimta - Pemetrexed - goedgekeurd door FDA en Europa voor niet-klein-cellige longkanker als onderhoudstherapie. Pointbreak fase 3 studie echter stopgezet wegens falen van Alimta

15 oktober 2012: Nieuwe studies hebben uitgewezen dat Alimta niet alle gevallen de beste aanpak is voor niet-klein-cellige longkanker: Lees de resultaten uit Pointbreak, een stopgezette fase III studie

2 november 2011: bron: Reuters en ASCO

Per direct wordt Alimta - pemetrexed nu ook in Europa aanbevolen als onderhoudsbehandeling voor niet-klein-cellige longkanker, ook als ander chemo's niet werken. Deze beslissing is genomen op basis van de PARAMOUNT studie. Zie onderaan artikel abstract van die gerandomiseerde placebo gecontroleerde fase III studie.

En lees ook hieronder wat Alimta - pemetrexed precies is. 11 juli 2009: Bron: ASCO 2009 en Medscape

Achtereenvolgens geplaatst artikelen met toestemming van FDA voor Alimta - Pemetrexed bij niet klein-cellige longkanker d.d. juli 2009 en daaronder toestemming FDA voor Alita - Pemetrexed i.p.v. chemokuren - maart 2005 voor mesothelioma.

De Amerikaanse Food and Drug Administration (FDA) heeft Alimnta - Pemetrexed ( Eli Lily) goedgekeurd als medicijn voor onderhoudstherapie van gevorderde of uitgezaaide niet-kleincellige longkanker (NSCLC). Alimta - Pemetrexed is het eerste geneesmiddel dat als onderhoudstherapie wordt goedgekeurd bij longkanker.

In een fase 3 trial onlangs gepresenteerd op ASCO 2009 kregen de patiënten ofwel Alimta - Pemetrexed (n = 441) of placebo (n = 222), samen met de beste ondersteunende zorg. Patiënten hadden gevorderde of gemetastaseerde (fase 3B of 4) NSCLC (zowel kleincellige en niet-kleincellige subtypen) die geen progressieve ziekte hadden na 4 cycli van de eerste op platina gebaseerde chemotherapie.
Voor alle patiënten in de studie, had de met Alimta - Pemetrexed behandelde groep een totale overleving van 13,4 maanden, tegenover 10,6 maanden voor de placebo groep. Echter, voor de niet-kleincellige subgroep, was de mediane algehele overleving 15,5 maanden voor patiënten in de Alimta - Pemetrexedgroep en 10,3 maanden voor patiënten met placebo. Het verschil was statistisch significant (p = .002).

Bron: Medscape

July 6, 2009 — The US Food and Drug Administration (FDA) has approved pemetrexed (Alimta, Eli Lily) for the maintenance therapy of advanced or metastatic nonsquamous non–small-cell lung cancer (NSCLC). Pemetrexed is the first drug indicated as a maintenance therapy in this setting.

"This drug represents a new approach in the treatment of advanced non–small-cell lung cancer," said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a press statement. "Typically, patients whose tumors respond to chemotherapy do not receive further treatment after four to six chemotherapy cycles. This study demonstrates an advantage in overall survival in certain patients who received Alimta for maintenance therapy."

In a phase 3 trial recently presented at the American Society of Clinical Oncology (ASCO) meeting, patients received either pemetrexed (n = 441) or placebo (n = 222), along with the best supportive care. Patients had advanced or metastatic (stage 3B or 4) NSCLC (both squamous and nonsquamous subtypes) that had not progressed after 4 cycles of initial platinum-based chemotherapy.

For all patients in the study, the pemetrexed treatment group had an overall survival of 13.4 months, compared with 10.6 months for the placebo group. However, for the nonsquamous subgroup, overall survival was 15.5 months for patients taking pemetrexed and 10.3 months for patients taking placebo. The difference was statistically significant (P = .002).

However, as reported by Medscape Oncology from ASCO, 2 lung-cancer experts attending the meeting questioned the appropriateness of using pemetrexed as a maintenance therapy. Neither was involved with this phase 3 trial.

"I don't think we have the answer as to when it is best to start pemetrexed. Should we start immediately after standard chemotherapy or later on? All you can say is that it improves survival in nonsquamous-cell patients. In my clinic, I will present maintenance therapy as an option," said Julie Brahmer, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, in Baltimore, Maryland.

"I endorse the use of pemetrexed as a second-line therapy for advanced non–small-cell lung cancer, but I don't think that all patients need immediate maintenance therapy following first-line treatment," said Nasser H. Hanna, MD, from the department of medicine at Indiana University, in Indianapolis, adding that the trial design did not allow it to definitively establish pemetrexed as a maintenance therapy.

Dr. Hanna explained the phase 3 trial was not designed to indicate whether maintenance therapy was superior to using pemetrexed at time of disease progression.

"Only 19 patients who were on placebo received pemetrexed at time of disease progression because, in part, the drug was not available at all of the centers involved in the study. In short, we know the drug improves survival but not that maintenance therapy is the best way to use it," he said.

A form of chemotherapy, pemetrexed is a folate analog metabolic inhibitor, which means that it disrupts metabolic processes that depend on the B-vitamin folate, a necessary ingredient for cell replication.

In the phase 3 study presented at ASCO, severe adverse effects (grade 3 or 4) were more common in the pemetrexed than in the placebo group, including fatigue (5% vs 0.5%) and low white-blood-cell counts (2.9% vs 0%).

Other reported adverse events included nausea, loss of appetite, tingling or numbness in the hands and feet, and skin rash, according to the FDA statement.

25 maart 2005 toegevoegd aan onderstaande berichtgeving: Op onze vraag naar al of niet vergoeden van Alimta kregen we dit antwoord van Eli Lily Nederland, de producent van Alimta. Ter informatie: Alimta is geregistreerd als medicijn tegen zowel mesothelioma als niet-klein-cellige longkanker, zie ook bericht daarover verderop in deze artikelenreeks, dus zou normaal gesproken gewoon vergoed moeten worden, maar we horen van verschillende patiënten dat zij dit niet vergoed krijgen vandaar onze vraag aan Eli Lily Nederland, of zij daarvan op de hoogte waren. Of dit antwoord nu betekent dat Alimta alleen voor patiënten met mesothelioma wordt vergoed en niet voor longkankerpatiënten weten we niet:

Geachte heer Braam,

Van mijn collega begreep ik dat u afgelopen dinsdag heeft gebeld in verband met vragen over de vergoeding van Alimta.
is het waar dat Alimta niet vergoed wordt?
waarom wordt Alimta niet vergoed?
er was een tijdje terug een persbericht uitgegaan waarin stond dat Alimta niet vergoed zou worden. Is het beleid van de minister inmiddels veranderd?

Ik wil u vriendelijk verzoeken om hierover contact op te nemen met de Vereniging Comite Asbestslachtoffers op tel. 0229265137 of www.comiteasbestslachtoffers.nl

Met vriendelijke groet,

Sjoukje DOP
Product Manager
Eli Lilly Nederland

27 augustus 2004: Bron: DOW: De FDA heeft afgelopen week goedkeuring gegeven aan Alimta, een medicijn tegen niet-klein-cellige longkanker, dat in studies minimaal zelfde resultaten gaf als taxol maar met veel minder bijwerkingen. Opvallend is dat in dit korte persbericht ook aanvullend B12 en foliumzuur wordt aanbevolen voor verminderen van bijwerkingen bij de behandeling van Alimta , maar ook andere chemokuren.

WASHINGTON (AP)--The Food and Drug Administration on Thursday approved a cancer drug made by pharmaceutical giant Eli Lilly & Co. (LLY) to treat advanced non-small cell lung cancer in patients who have undergone chemotherapy. According to the American Cancer Society, non-small cell lung cancer is the leading cause of cancer-related deaths in the nation. Eighty percent of 174,000 new lung cancer cases diagnosed each year are non-small cell lung cancer. By the time most patients arrive for treatment, the cancer is widespread. The drug, Alimta, in clinical trials was found to shrink tumors as effectively as another cancer-fighting drug, Taxotere. But Alimta did so with fewer troubling side effects, which include hair loss, tingling fingers and toes, depressed blood count, and hospitalizations for subsequent infection. "Lung cancer is a very devastating disease and the therapies can be hard on patients," said Roy Herbst, chief of thoracic oncology at MD Anderson Cancer Center. The Houston facility sees nearly 1,500 new lung cancer patients per year and treated at least 20 in the Alimta versus Taxotere study. One in 50 patients taking Alimta had side effects. That benefit came without any lessening of the drug's effectiveness. That's significant as cancer care moves toward more combination drug or sequential therapies, Herbst said. "We can only do that if the drugs we give (patients) leave them in a state ... where they're still strong. You can kill the cancer, but leave the patient feeling well," he said. The Alimta treatment, 500 mg every 21 days, costs patients $3,900 per month, according to the company. The anti-cancer drug works by interfering with three enzymes on which tumors depend. "There's no question, the survival was comparable to the survival with the best drugs we have," said Dr. Paul Bunn, director of the University of Colorado Cancer Center and principal investigator for the clinical trial. "This drug is as good as anything else we have. It does benefit patients." Dr. Richard Gralla, president of the New York Lung Cancer Alliance, estimated tens of thousands of lung-cancer patients per year would be eligible to take Alimta. The trial tested a simple way to reduce side effects: Taking Alimta in concert with folate pills and B-12 injections. "When you take those special B vitamins, it further reduces the side effects of the chemotherapy," Gralla said.

Phase III study of maintenance pemetrexed (pem) plus best supportive care (BSC) versus placebo plus BSC immediately following induction treatment with pem plus cisplatin for advanced nonsquamous non-small cell lung cancer (NSCLC).

Source: ASCO en J Clin Oncol 29: 2011 (suppl; abstr CRA7510)

Author(s):

L. G. Paz-Ares, F. De Marinis, M. Dediu, M. Thomas, J. Pujol, P. Bidoli, O. Molinier, T. P. Sahoo, E. Laack, M. Reck, J. Corral, S. A. Melemed, W. J. John, N. Chouaki, A. Zimmerman, C. M. Visseren Grul, C. Gridelli; Hospital Universitario Virgen del Rocío, Seville, Spain; San Camillo-Forlanini Hospital, Rome, Italy; Medical Oncology Department, Institute of Oncology, Bucharest, Romania; Thoraxklinik at the University of Heidelberg, Heidelberg, Germany; Montpellier University Hospital, Montpellier, France; Az Ospedale S. Gerardo, Monza, Italy; Le Mans Regional Hospital, Le Mans, France; Jawaharlal Nehru Cancer Hospital and Research Centre, Bhopal, India; Ambulantes Krebszentrum Hamburg, Hamburg, Germany; Hospital Großhansdorf, Großhansdorf, Germany; Eli Lilly & Co., Indianapolis, IN; Lilly France, Paris, France; Lilly Oncology Europe, Houten, Netherlands; SG Moscati Hospital, Avellino, Italy

Abstract:

Background: The PARAMOUNT trial investigated whether pem continuation maintenance therapy improves progression-free survival (PFS) after pem-cisplatin induction therapy in patients (pts) with advanced nonsquamous NSCLC.

Methods: In this double-blind, placebo-controlled trial, 939 pts participated in the induction phase, specified as four cycles of induction pem (500 mg/m²) and cisplatin (75 mg/m²) on day 1 of a 21-day cycle. Pts who had not progressed during pem-cisplatin induction and had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (n=539; 57.4%) were randomized (2:1, stratified for disease stage, PS, and induction response) to maintenance pem (500 mg/m² on day 1 of a 21-day cycle) plus BSC (n=359) or placebo plus BSC (n=180) until disease progression. All pts received vitamin B₁₂, folic acid, and dexamethasone. The primary endpoint was PFS (target: HR=0.65, two-sided alpha=0.05; 90% power with minimum of 238 events).

Results: Pt characteristics were balanced between arms: median age=61 years; 58% male; 95% Caucasian; 32% PS 0; 91% stage IV; 87% adenocarcinoma; and 45% induction complete/partial response. Pem continuation maintenance resulted in a 36% reduction in the risk of progression (HR=0.64, 95% CI: 0.51-0.81; P=0.00025). The median independently reviewed PFS (472 pts, 297 events), measured from randomization, was 3.9 months (95% CI: 3.0-4.2) on the pem arm, and 2.6 months (95% CI: 2.2-2.9) on the placebo arm. The disease control rate (% pts with response/stable disease) was 71.8% on the pem arm, and 59.6% on the placebo arm (P=0.009). The drug-related serious adverse event (AE) rate was 8.9% on the pem arm, and 9.2% of pts had grade 3/4 laboratory Common Toxicity Criteria AEs. On the placebo arm, the rates were 2.8% and 0.6%, respectively. Discontinuations due to AEs were 5.3% on the pem arm, 3.3% on the placebo arm.

Conclusions: PARAMOUNT met its primary endpoint and showed that pem continuation maintenance following pem-cisplatin induction is an effective and well tolerated treatment for pts with advanced nonsquamous NSCLC.

mesothelioma, longkanker, alimta, pemetrexed, meosthelioma, cisplatin, paclitaxel