During the past week, the UK's National Institute for Health and Clinical Excellence (NICE) has issued mixed recommendations on the use of drugs for the treatment of renal cell carcinoma (RCC) and metastatic colorectal cancer (MCRC).
NICE has not recommended Genentech's (Roche) Avastin (bevacizumab), Bayer HealthCare/Onyx Pharmaceuticals' Nexavar (sorafenib) and Wyeth Pharmaceuticals' Torisel (temsirolimus) as first-line treatment options for advanced and/or metastatic RCC. In addition, Nexavar and Pfizer's Sutent (sunitinib) are not recommended for second-line treatment, although both are licensed in the EU for this therapy. According to NICE, the evidence to support the use of the first- and second-line treatments is not strong enough to justify using NHS funds, which could be used for other cancer treatment programmes or in other treatment areas.
In response to this NICE decision, Roche is considering all options. The Appraisal Committee accepted that Avastin in combination with interferon has a similar clinical and cost-effectiveness profile to the already-approved Sutent, but turned it down because it has a licence in other indications, despite the fact that these indications are not currently routinely reimbursed on the NHS.
John Melville, General Manager of Roche UK, commented: "this decision is entirely illogical and neither addresses the needs of patients with renal cancer, nor advances the innovation agenda. Avastin demonstrates the same value to the NHS as sunitinib and this guidance goes against the spirit of end-of-life criteria, which were devised for this very setting."
On a positive note, NICE has recommended the use of Merck Serono's (Merck KGaA) Erbitux (cetuximab) in combination with FOLFOX for the first-line treatment of MCRC, but only when all of the following criteria are met: (a) the primary colorectal tumour has been resected or is potentially operable; (b) the metastatic disease is confined to the liver and is unresectable; (c) the patient is fit enough to undergo surgery to resect the primary colorectal tumour and to undergo liver surgery if the metastases become resectable after treatment with Erbitux; and (d) the manufacturer rebates 16 per cent of the amount of Erbitux used on a per patient basis.
Further, NICE recommended that patients who meet the above criteria should receive treatment with Erbitux for no more than 16 weeks. After this period, treatment with Erbitux should stop and the patient should be assessed for resection of liver metastases. It was also recommended that people with MCRC with metastatic disease confined to the liver who receive Erbitux should have their treatment managed only by multidisciplinary teams that involve highly-specialised liver surgical services. The Appraisal Committee concluded that under the specific circumstances outlined in the guidance, the cost of Erbitux in relation to how well it works is an effective use of NHS resources.
Although the NICE guidance on the use of Erbitux means many MCRC patients will have a new treatment opinion, the decision not to recommend Avastin, Nexavar or Torisel as a first-line therapy for RCC will reduce treatment options for UK patients who are fighting this disease, yet is available for the same indication in comparable countries.
Alice Rossiter - Cancer Drug News Editor
Showing posts with label Avastin. Show all posts
Showing posts with label Avastin. Show all posts
Tuesday, September 1, 2009
Thursday, February 19, 2009
NICE and SMC tighten purse strings
The UK's National Institute for Health and Clinical Excellence (NICE) has issued its final appraisal document recommending the use of Pfizer's Sutent (sunitinib) as a first-line treatment for patients with metastatic renal cell carcinoma (RCC). However, sunitinib is the only one of four drugs being appraised that has been preliminarily cleared for use on the NHS, once again raising the question of drug access in the UK compared to the rest of Europe.
NICE is also currently appraising the use of Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib) and Wyeth's Torisel (temsirolimus) for the treatment of advanced and/or metastatic RCC. Following the independent advisory Committee meeting on 14th January, NICE has decided to split this appraisal in two in order to get guidance out to the NHS as quickly as possible. In the first appraisal, sunitinib is recommended as a first-line treatment option in advanced and/or metastatic RCC for patients who are suitable for immunotherapy with an ECOG performance status of 0 or 1. Sunitinib demonstrated a significant improvement in progression-free survival versus interferon alpha. The median survival of patients treated with sunitinib exceeded two years. In September 2008, NICE had issued an appraisal consultation document that advised against the use of all four medicines for the treatment of advanced and/or metastatic RCC. The latest announcement reverses NICE's previous recommendation regarding the coverage of sunitinib, making it the only one of the four medicines under review, that is so far recommended for coverage.
Sunitinib, an oral multi-kinase inhibitor, was first approved in January 2006 for advanced RCC. The drug works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Pfizer has agreed a patient access scheme with the Department of Health, in which the first treatment cycle of sunitinib is free to the NHS.
In the second appraisal, bevacizumab, sorafenib and temsirolimus are not recommended as first-line treatment options for advanced and/or metastatic RCC. In addition, the two drugs also licensed for second-line treatment of advanced or metastatic RCC, sorafenib and sunitinib, are not recommended for this indication. Guidance on bevacizumab, sorafenib and temsirolimus for first-line treatment and sorafenib and sunitinib for the second-line treatment of RCC is available for public consultation via NICE until 4th March.
In a statement from Wyeth, the company commented that it believes that denying patients access to the benefits of temsirolimus in extending life-expectancy compared to standard existing therapy is a devastating and cruel blow to patients and their families. Temsirolimus, despite being found to be clinically effective, has been deemed not to be cost-effective in the current assessment.
Similarly disappointing news was announced in Scotland, as the Scottish Medicines Consortium (SMC) published its guidance on the use of GSK's Tyverb (lapatinib) and Eli Lilly's Alimta (pemetrexed), ruling that in both cases the manufacturer did not present a sufficiently robust economic case to gain acceptance. Lapatinib is approved in Europe, in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer, while pemetrexed is indicated, in combination with cisplatin, for the first-line treatment of patients with locally-advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Despite clinical evidence that the two drugs can extend patients' lives by around two months and six weeks, respectively, the price that this comes at is still not seen as cost-effective.
Matthew Dennis - Editor, Cancer Drug News
NICE is also currently appraising the use of Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib) and Wyeth's Torisel (temsirolimus) for the treatment of advanced and/or metastatic RCC. Following the independent advisory Committee meeting on 14th January, NICE has decided to split this appraisal in two in order to get guidance out to the NHS as quickly as possible. In the first appraisal, sunitinib is recommended as a first-line treatment option in advanced and/or metastatic RCC for patients who are suitable for immunotherapy with an ECOG performance status of 0 or 1. Sunitinib demonstrated a significant improvement in progression-free survival versus interferon alpha. The median survival of patients treated with sunitinib exceeded two years. In September 2008, NICE had issued an appraisal consultation document that advised against the use of all four medicines for the treatment of advanced and/or metastatic RCC. The latest announcement reverses NICE's previous recommendation regarding the coverage of sunitinib, making it the only one of the four medicines under review, that is so far recommended for coverage.
Sunitinib, an oral multi-kinase inhibitor, was first approved in January 2006 for advanced RCC. The drug works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Pfizer has agreed a patient access scheme with the Department of Health, in which the first treatment cycle of sunitinib is free to the NHS.
In the second appraisal, bevacizumab, sorafenib and temsirolimus are not recommended as first-line treatment options for advanced and/or metastatic RCC. In addition, the two drugs also licensed for second-line treatment of advanced or metastatic RCC, sorafenib and sunitinib, are not recommended for this indication. Guidance on bevacizumab, sorafenib and temsirolimus for first-line treatment and sorafenib and sunitinib for the second-line treatment of RCC is available for public consultation via NICE until 4th March.
In a statement from Wyeth, the company commented that it believes that denying patients access to the benefits of temsirolimus in extending life-expectancy compared to standard existing therapy is a devastating and cruel blow to patients and their families. Temsirolimus, despite being found to be clinically effective, has been deemed not to be cost-effective in the current assessment.
Similarly disappointing news was announced in Scotland, as the Scottish Medicines Consortium (SMC) published its guidance on the use of GSK's Tyverb (lapatinib) and Eli Lilly's Alimta (pemetrexed), ruling that in both cases the manufacturer did not present a sufficiently robust economic case to gain acceptance. Lapatinib is approved in Europe, in combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer, while pemetrexed is indicated, in combination with cisplatin, for the first-line treatment of patients with locally-advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology. Despite clinical evidence that the two drugs can extend patients' lives by around two months and six weeks, respectively, the price that this comes at is still not seen as cost-effective.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, February 4, 2009
ATLAS meets primary endpoint
The Phase III ATLAS (AVF3671g) study investigating Tarceva (erlotinib) in combination with Avastin (bevacizumab) as maintenance therapy following initial treatment with bevacizumab plus chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC) has met its primary endpoint. The trial was stopped early on the recommendation of an independent Data Safety Monitoring Board after a preplanned interim analysis showed that combining erlotinib and bevacizumab significantly extended the time patients lived without their disease advancing, as defined by progression-free survival (PFS), compared to bevacizumab plus placebo. A preliminary safety analysis showed adverse events were consistent with previous erlotinib and bevacizumab studies, as well as trials evaluating the two medicines together, and no new safety signals were observed.
The global, multi-centre, randomised, double-blind, placebo-controlled study enrolled 1,157 patients with locally-advanced, recurrent or metastatic NSCLC. In order to evaluate patients who are often excluded from bevacizumab-based trials, patients with treated brain metastases, tumours of squamous cell histology that were not centrally located in the lung and those taking blood-thinning medications were eligible for this trial. Subjects were initially treated with four cycles of bevacizumab in combination with the investigators' choice of platinum-based CT regimens (carboplatin+gemcitabine, carboplatin+paclitaxel, carboplatin+docetaxel, cisplatin+vinorelbine, cisplatin+docetaxel or cisplatin+gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomised (n=768) to receive maintenance therapy with bevacizumab+erlotinib or bevacizumab+placebo until disease progression.
The study's primary endpoint of PFS, as determined by investigators, was defined as the length of time from randomisation to disease progression or death from any cause. PFS assessment began from the start of the maintenance phase of the study after initial treatment with four cycles of bevacizumab and CT. Secondary endpoints included overall survival (OS), incidence of all adverse events and selected Grade 3 or greater adverse events and incidence of treatment discontinuation for reasons other than disease progression.
An earlier study, called BeTa Lung, which evaluated bevacizumab in combination with erlotinib in patients with advanced NSCLC whose disease had progressed following platinum-based CT, failed to meet its primary endpoint of improving OS compared to erlotinib in combination with placebo. However, there was clear evidence of clinical activity, with improvements in the secondary endpoints of PFS and response rate when bevacizumab was added to erlotinib compared to erlotinib alone. An additional trial, called SATURN, showed that erlotinib delayed disease progression when given as a single agent immediately following treatment with CT, compared to placebo. In ATLAS, patients were initially treated with bevacizumab plus CT followed by the addition of erlotinib to bevacizumab in the maintenance phase. Genentech plans to discuss these data with the FDA to determine next steps.
Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel for patients with locally-advanced, non-squamous NSCLC, based on a 25 per cent improvement in OS compared to CT alone (hazard ratio=0.80). Tarceva is currently approved as a treatment for patients with advanced NSCLC who have progressed following treatment with at least one prior CT regimen, based on a 37 per cent improvement in OS compared to placebo (hazard ratio=0.73). OSI Pharmaceuticals markets Tarceva through partnerships with Genentech in the US and Roche throughout the rest of the world. Avastin is jointly marketed by Genentech and Roche.
Matthew Dennis - Editor, Cancer Drug News
The global, multi-centre, randomised, double-blind, placebo-controlled study enrolled 1,157 patients with locally-advanced, recurrent or metastatic NSCLC. In order to evaluate patients who are often excluded from bevacizumab-based trials, patients with treated brain metastases, tumours of squamous cell histology that were not centrally located in the lung and those taking blood-thinning medications were eligible for this trial. Subjects were initially treated with four cycles of bevacizumab in combination with the investigators' choice of platinum-based CT regimens (carboplatin+gemcitabine, carboplatin+paclitaxel, carboplatin+docetaxel, cisplatin+vinorelbine, cisplatin+docetaxel or cisplatin+gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomised (n=768) to receive maintenance therapy with bevacizumab+erlotinib or bevacizumab+placebo until disease progression.
The study's primary endpoint of PFS, as determined by investigators, was defined as the length of time from randomisation to disease progression or death from any cause. PFS assessment began from the start of the maintenance phase of the study after initial treatment with four cycles of bevacizumab and CT. Secondary endpoints included overall survival (OS), incidence of all adverse events and selected Grade 3 or greater adverse events and incidence of treatment discontinuation for reasons other than disease progression.
An earlier study, called BeTa Lung, which evaluated bevacizumab in combination with erlotinib in patients with advanced NSCLC whose disease had progressed following platinum-based CT, failed to meet its primary endpoint of improving OS compared to erlotinib in combination with placebo. However, there was clear evidence of clinical activity, with improvements in the secondary endpoints of PFS and response rate when bevacizumab was added to erlotinib compared to erlotinib alone. An additional trial, called SATURN, showed that erlotinib delayed disease progression when given as a single agent immediately following treatment with CT, compared to placebo. In ATLAS, patients were initially treated with bevacizumab plus CT followed by the addition of erlotinib to bevacizumab in the maintenance phase. Genentech plans to discuss these data with the FDA to determine next steps.
Avastin is currently approved as first-line treatment in combination with carboplatin and paclitaxel for patients with locally-advanced, non-squamous NSCLC, based on a 25 per cent improvement in OS compared to CT alone (hazard ratio=0.80). Tarceva is currently approved as a treatment for patients with advanced NSCLC who have progressed following treatment with at least one prior CT regimen, based on a 37 per cent improvement in OS compared to placebo (hazard ratio=0.73). OSI Pharmaceuticals markets Tarceva through partnerships with Genentech in the US and Roche throughout the rest of the world. Avastin is jointly marketed by Genentech and Roche.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, August 13, 2008
Draft NICE guidance denies RCC drugs
The UK's National Institute for Health and Clinical Excellence (NICE) has issued preliminary recommendations for the treatment of renal cell carcinoma (RCC), concluding that Roche/Genentech's Avastin (bevacizumab), Bayer/Onyx Pharmaceuticals' Nexavar (sorafenib), Pfizer's Sutent (sunitinib) and Wyeth Pharmaceuticals' Torisel (temsirolimus) are not recommended as treatment options for advanced and/or metastatic disease. Although the drugs were shown to be clinically effective and extend life for RCC patients, they were deemed to not be a cost-effective use of NHS resources. NICE is expected to issue final guidance in January 2009.
Following the decision, Cancer Research UK (CRUK) has called for NICE to alter the way that it appraises the value of drugs for rare diseases, such as metastatic RCC, where clinical benefit is proven but evidence is limited due to the small number of available patients. Professor Peter Johnson, CRUK's chief clinician, stated: "We are disappointed at NICE's view that although these drugs are clinically effective, their high price means that they are not considered to be value for money for the NHS. These drugs have shown a small but definite improvement in an illness where there are few alternative treatments. If this decision stands it will be very frustrating for cancer patients and their clinicians."
The charity put forward that possible solutions include looking at the way that pharmaceutical companies are charging the NHS for drugs, and whether appropriate allowances are being made by NICE to compensate for the lack of large-scale trials in these areas. However, it turns out that proposals were submitted by two of the manufacturers relating to drug acquisition costs. But these were not considered by the Department of Health as they had not been agreed before the appraisal.
The preliminary guidance raises questions as to how NICE evaluates cancer drugs, particularly for cancers that only affect a relatively small number of people. The gold-standard method of testing whether a treatment works and is safe is through the use of clinical trials. The larger the number of patients enrolled in a study, and the longer it lasts, the more sure researchers can be about its results. This works for diseases that affect large numbers of people, such as breast and lung cancer, but only around 2,000 people every year are diagnosed with metastatic RCC. Further, only one in ten people diagnosed with this stage of the disease is alive five years later. This means that for relatively rare diseases like this, it can take a long time to conduct large enough studies to gather the evidence needed to gain approval from regulatory agencies.
Even if these studies do demonstrate benefit, as those for the four drugs did, there is still the cost-effectiveness hurdle to overcome. When NICE analysed the data from the trials with its models, it found that the drugs were expensive (around £20,000 to £35,000 per patient per year) compared to the benefit they brought patients. However, concerns have also been raised about these models, which are designed to examine giving drugs to large numbers of people. Are they equally valid for looking at relatively uncommon diseases, such as metastatic RCC? Hopefully NICE will be able to answer these questions when its final guidance is published.
Matthew Dennis - Editor, Cancer Drug News
Following the decision, Cancer Research UK (CRUK) has called for NICE to alter the way that it appraises the value of drugs for rare diseases, such as metastatic RCC, where clinical benefit is proven but evidence is limited due to the small number of available patients. Professor Peter Johnson, CRUK's chief clinician, stated: "We are disappointed at NICE's view that although these drugs are clinically effective, their high price means that they are not considered to be value for money for the NHS. These drugs have shown a small but definite improvement in an illness where there are few alternative treatments. If this decision stands it will be very frustrating for cancer patients and their clinicians."
The charity put forward that possible solutions include looking at the way that pharmaceutical companies are charging the NHS for drugs, and whether appropriate allowances are being made by NICE to compensate for the lack of large-scale trials in these areas. However, it turns out that proposals were submitted by two of the manufacturers relating to drug acquisition costs. But these were not considered by the Department of Health as they had not been agreed before the appraisal.
The preliminary guidance raises questions as to how NICE evaluates cancer drugs, particularly for cancers that only affect a relatively small number of people. The gold-standard method of testing whether a treatment works and is safe is through the use of clinical trials. The larger the number of patients enrolled in a study, and the longer it lasts, the more sure researchers can be about its results. This works for diseases that affect large numbers of people, such as breast and lung cancer, but only around 2,000 people every year are diagnosed with metastatic RCC. Further, only one in ten people diagnosed with this stage of the disease is alive five years later. This means that for relatively rare diseases like this, it can take a long time to conduct large enough studies to gather the evidence needed to gain approval from regulatory agencies.
Even if these studies do demonstrate benefit, as those for the four drugs did, there is still the cost-effectiveness hurdle to overcome. When NICE analysed the data from the trials with its models, it found that the drugs were expensive (around £20,000 to £35,000 per patient per year) compared to the benefit they brought patients. However, concerns have also been raised about these models, which are designed to examine giving drugs to large numbers of people. Are they equally valid for looking at relatively uncommon diseases, such as metastatic RCC? Hopefully NICE will be able to answer these questions when its final guidance is published.
Matthew Dennis - Editor, Cancer Drug News
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