Waarschuwing in the Lancet voor euforie over Herceptin. na toch uitstekende resultaten uit een fase III studie met Herceptin en borstkankerpatiënten.

4 december 2011: wellicht goed om te lezen is de nieuwste publicatie over herceptin plus een vaccin (E-75), welke voor 60 procent van de vrouwen met borstkanker geschikt zou zijn en in een lopende studie bewijst dat het risico op een recidief met maar liefst 57% vermindert als aan herceptin het vaccin wordt toegevoegd. Onderstaand artikel verscheen al in 2005 in the Lancet. Misschien zijn de meningen bijgesteld?

14 november 2005: Bron: The Guardian - Herceptin article en The Lancet

In The Lancet verschijnt deze week een artikel waarin in een hoofd redactioneel commentaar wordt gewaarschuwd voor de euforie rondom Herceptin bij borstkanker. Zie voor volledig hoofdredactioneel commentaar van The Lancet onder deze inleiding en artikel uit The Herald Tribune. Wel heel opmerkelijk dat dit al zo snel gebeurt en zeker zo scherp afwijzend nadat deze maand grote publicaties van enkele grote gerandomiseerde studies aangeven dat voor bepaalde vormen van borstkanker Herceptin samen met standaard chemokuren een hoog significant beter resultaat geeft dan standaard chemokuren voor borstkanker. Nu waarschuwt the Lancet dat de publicaties gebaseerd zouden zijn op te weinig echt groot onderzoek, dat Herceptin alleen voor gevorderde borstkankerpatiënten geschikt zou zijn en ook onderzocht en niet voor beginnende borstkanker en dat de bijwerkingen van Herceptin groter en ernstiger zouden zijn dan bv. taxol. Hier wordt verwezen naar een passage uti een studie dat enkele patiënten ernstig hartfalen hadden gekregen. Dat Herceptin alleen geregistreerd zou zijn voor gevorderde borstkanker klopt wel maar zou juist een deze maand gepubliceerde fase III studie geeft Herceptin als aanvulling op postoperatieve aanpak maar liefst 52% minder kans op recidieven bij geopereerde borstkankerpatiënten stadium I en II. Dus toch echt beginnende borstkanker en met alleen Herceptin vergeleken met alleen standaard chemo. Waarom The Lancet dan toch het argument aanvoert van registratie is toch beetje vreemd vinden wij. Avastin voor uitgezaaide darmkanker, borstkanker, longkanker enz. is bv. voor bijna geen enkele vorm van kanker al geregistreerd maar wordt wereldwijd algemeen aangeboden en enorm over gepubliceerd terwijl de resultaten van Avastin erg weinig echte verbetering laten zien t.o.v. van andere behandelvormen, zelfs bij uitgezaaide darmkanker. En dat de bijwerkingen veel en veel ernstiger zouden zijn valt o.i. ook wel mee als we de studieresultaten bekijken waarin de bijwerkingen worden beschreven. Slechts enkele vrouwen op een grote groep hadden last van hartfalen, hoewel dit wel significant was, dus wellicht heeft The lancet hiermee wel een punt. Maar goed hier een artikel over het artikel dat in The Lancet verscheen uit de International Herald Tribune, een zogeheten kwaliteitskrant. We zoeken nog het artikel uit the Lancet zelf.

November 10, 2005 - International Herald Tribune.

By Elisabeth Rosenthal

NEW YORK Just three weeks after America's most prestigious medical journal declared an expensive new cancer drug to be "revolutionary" and "maybe even a cure" for early breast cancer, the most prominent British medical journal came to the opposite conclusion Wednesday.
"The available evidence is insufficient to make reliable judgments," editors of The Lancet wrote in an editorial published online Wednesday. "It is profoundly misleading to suggest, even rhetorically, that the published data may be indicative of a cure for breast cancer."
In a telephone interview, The Lancet's chief editor, Dr. Richard Horton, said he was "quite angry" that Herceptin has been portrayed as such a wonder drug in The Lancet's U.S. counterpart, the New England Journal of Medicine. "Study results are preliminary, inconsistent and raise extremely serious concerns about safety," he said.
Herceptin is designed to treat women with breast tumors that bear a common genetic mutation associated with aggressive disease that responds poorly to conventional treatments. The buzz surrounding Herceptin has led patient groups worldwide to demand the drug from governments and insurers, even though it is not licensed for early-stage breast cancer. It is approved only for use in advanced cancers. The buzz intensified last month, when the New England Journal of Medicine published two preliminary studies concluding that the drug seemed to be extremely effective, accompanied by a glowing editorial.

The Lancet decided to publish its editorial early and online Wednesday, Horton said, after the British health secretary, Patricia Hewitt, publicly demanded the National Health Service to provide the drug to a patient who had sued to be given the medicine. In France, pressure to release Herceptin was so intense that regulators bypassed normal channels earlier this year to make it more widely available to breast cancer patients. At cost of about 35,000, or about $41,200, for a full treatment course, governments have been hard pressed to pay for Herceptin. But Horton said the current debate was simply about whether the drug worked and was safe. "The last thing we should want is to have a politician campaigning on behalf of a drug," Horton said. "It's a crazy way to make what should be a scientific decision." Katja Prowald, a spokeswoman for Roche, the Swiss company that markets Herceptin in Europe, said scientists at the company had "read the editorial and said that the statements it contained were not correct." The company will release a further analysis by Thursday, she said, noting that Roche was currently busy answering questions about Tamiflu, a Roche drug that many countries are stockpiling against bird flu. The dispute surrounding Herceptin began earlier this year when researchers, at a meeting of the American Cancer Society, presented promising early data on the use of Herceptin to treat early breast cancer. Two articles, containing further interim data, were published in the New England Journal of Medicine on Oct. 20.

The studies were funded in part by Genentech, the company that developed the drug, and by Roche. According to the studies, women who received Herceptin along with standard chemotherapy had half the rate of recurrence after one year than those who did not receive the drug. Researchers from a consortium of prestigious international medical centers considered the results compelling enough that women who had been in the study's control group, who initially received no Herceptin, were belatedly offered the medicine. But some scientists have long had misgivings about the data, or at least the drug's golden image.

Last week in the Journal of the American Medical Association, Dr. Victor Montori of McMaster University in Toronto pointed out that when trials are stopped early, the preliminary analyses can show "implausibly large treatment effects," and he urged "skepticism" in viewing the data. Horton pointed out that one of the New England Journal of Medicine articles combines data from two patient trials that may not be comparable.

Also, he noted that a small but significant number of women receiving Herceptin develop severe heart failure, and that problem has not yet been adequately studied. He said the hoopla surrounding Herceptin resulted from a synergy between desperate patients desiring better treatments and drug companies looking for profit, creating what he called an "unholy alliance." He urged that regulatory review boards be given the time necessary to thoroughly evaluate the drug, saying: "We need to have a strong spine to make sure that scientific evaluation remains scientific and is not dominated by politics." The Lancet said: "The debate about the availability of Herceptin to women with early breast cancer demands cooler heads than have so far prevailed, in politics, in public, and even in medical journals."

SOURCE-
Herceptin article

Bron: The Lancet 2005; 366:1673

DOI:10.1016/S0140-6736(05)67670-2

Herceptin and early breast cancer: a moment for caution It is no surprise that patients with cancer, together with leading cancer charities, are calling for the faster approval of drugs they see as life saving. One UK charity, Cancer Bacup, has identified a “dossier of delay” in current procedures. The chief culprit in Britain is said to be the National Institute for Health and Clinical Excellence (NICE). The story is not so simple. Under considerable political and media pressure, NICE and the Department of Health last week announced the launch of a rapid process for assessing new and potentially life-saving medicines. Five drugs have been targeted for fast-track: trastuzumab (Herceptin), docetaxel, and paclitaxel for breast cancer; rituximab for non-Hodgkin's lymphoma; and bortezomib for multiple myeloma. While these developments show commendable responsiveness to public concern, they must not be allowed to undermine NICE's hard-won and well-deserved reputation for independence and scientific rigour. Herceptin is a case in point. In March, 2002, NICE recommended Herceptin for use in women with HER2-positive advanced breast cancer, either alone or in combination with paclitaxel. The process leading to this decision was criticised for taking too long. NICE justified its timing by pointing out the need for careful and thoughtful scrutiny of the available data by an independent advisory committee. NICE's principal concern was to provide reliable advice. Their spokeswoman noted that, “we felt it right that we allow the independent committee that advises NICE the time it needed to analyse and consider this evidence before they gave us their final advice”. This view is surely correct. Whatever the sense of urgency, it is crucial that NICE resists pressure to make expedient decisions. Three years on, a similar but even more intense debate surrounds the use of Herceptin for early breast cancer. Promising results were initially presented at this year's American Society of Clinical Oncology annual meeting. An immediate wave of demand for Herceptin grew, despite the fact that the drug was not only unlicensed for this indication but also that its manufacturer, Roche, had not even submitted data for the drug's approval. Some countries, such as France, bypassed their official approvals procedure to make Herceptin available. In October, these studies were finally reported in the New England Journal of Medicine. In an accompanying editorial, Dr Gabriel Hortobagyi described the results as “simply stunning” and “revolutionary”. He even went so far as to say that Herceptin was “maybe even a cure” for breast cancer. Naturally this comment was picked up and repeated across the world, fuelling demand for rapid access to Herceptin. The excitement is premature. The studies so far reported represent interim efficacy analyses. As Victor Montori and colleagues advised in last week's JAMA, such analyses may “show implausibly large treatment effects”. They recommend that “clinicians should view the results of such trials with scepticism”. The two NEJM reports use different dosing regimens, making comparisons and conclusions additionally more difficult. It is especially hard to tease apart the results because one of the papers combines results from two trials sponsored by Genentech. Although the “joint analysis was developed and analysed” by both trial teams, it is not made clear whether this synthesis was planned in advance of the start of both trials. The report merely notes that the US FDA and National Cancer Institute approved the joint analysis plan, which may reflect the expectation that neither trial alone would demonstrate a positive result. Comparisons are further hampered by the omission of crucial overall and disease-free survival data, as well as information on cardiotoxicity. However, it is clear that Herceptin can precipitate severe heart failure in some patients. The best that can be said about Herceptin's efficacy and safety for the treatment of early breast cancer is that the available evidence is insufficient to make reliable judgments. It is profoundly misleading to suggest, even rhetorically, that the published data may be indicative of a cure for breast cancer. Drug regulatory agencies and bodies such as NICE play an important part in translating research evidence into clinical guidance. It is vital that their decisions are made carefully after considering the totality of available evidence. They must be free from political, special interest, or media influence, no matter how well meaning. The debate about the availability of Herceptin to women with early breast cancer demands cooler heads than have so far prevailed, in politics, in public, and even in medical journals. The Lancet