Patients suffering from an aggressive form of breast cancer (BC) are being failed by the NHS and deprived of more treatment options as the National Institute for Health and Clinical Excellence (NICE) rejects GlaxoSmithKline's oral Tyverb (lapatinib) in combination with capecitabine for the treatment of ErbB2-positive BC.
BC is now the most common cancer in the UK. In 2006, >45,500 women were diagnosed with the disease; that is approximately 125 women a day, and in the last ten years, incidence rates in the UK have increased by 6 per cent. As an oral treatment, lapatinib gives patients suffering from ErbB2-positive BC the freedom to spend precious additional months with friends and family without the restrictive ties of regular hospital visits.
The decision to deny NHS patients access to treatment with lapatinib follows the request in July by NICE's Appeal Panel that the Appraisal Committee should reconsider lapatinib under the Institute's end of life (EOL) supplementary guidance. The EOL guidance was specifically developed to help small numbers of patients who have only a few months to live, gain access to important new medicines. GSK submitted additional data demonstrating that lapatinib met all three of the EOL criteria.
NICE recognised that lapatinib met the EOL criteria, acknowledging that additional data submitted by GSK demonstrated that the drug could offer a significant extension to life, but it felt lapatinib was still not a cost-effective use of NHS resources. This decision has been made despite GSK offering the Tyverb patient access programme, which allows NHS patients in the UK free access to lapatinib for the first three months of treatment.
GSK proposed the patient access programme in the UK when NICE indicated early on in its review that it did not consider lapatinib to be cost effective in treating this patient population. The company will continue to honour the access programme for NHS trusts in the UK. A total of 26 trusts have already enrolled in this programme, reflecting the clinical demand for lapatinib and recognising the potential cost effectiveness for the NHS. Simon Jose, General Manager of GSK UK commented: "it is disappointing that, despite acknowledging Tyverb meets these criteria and GSK offering to bear the cost of lapatinib for up to 12 weeks, NICE is still proposing to reject lapatinib. We will continue to offer our patient access programme to individual NHS Trusts to ensure patients have access to Tyverb."
This decision will result in 2,000 UK women a year being denied access to lapatinib on the NHS. These are women for whom there are very few other treatment options available to them at this stage of their disease. By comparison, lapatinib is funded in 18 other European countries for the treatment of women whose advanced BC has returned despite treatment with standard chemotherapy regimes, including intravenous Herceptin (trastuzumab).
Alice Rossiter - Cancer Drug News Editor
Showing posts with label lapatinib. Show all posts
Showing posts with label lapatinib. Show all posts
Wednesday, October 28, 2009
Wednesday, April 8, 2009
GSK looks to expand use of lapatinib; to appeal NICE decision
GlaxoSmithKline has simultaneously submitted regulatory applications in the EU and US to expand the use of Tyverb/Tykerb (lapatinib) to include the first-line treatment of breast cancer (BC). The variation to the EU marketing authorisation and the sNDA were submitted, respectively, to the EMEA and to the FDA for the combination of lapatinib plus an aromatase inhibitor for use in patients with hormone-sensitive, metastatic BC.
The submissions are based on results from the recent EGF30008 study, which evaluated lapatinib plus Novartis' aromatase inhibitor, Femara (letrozole), in women with hormone receptor-positive metastatic BC that may or may not overexpress the HER2-positive receptor. Results from the study showed that women experienced a 5.2 month increase in median progression-free survival when treated with lapatinib+letrozole, compared to those treated with letrozole alone. Results from the intent-to-treat group showed that lapatinib+letrozole provided an additional 1.1 month before disease progression, compared to letrozole treatment alone.
Lapatinib, in combination with capecitabine, is currently authorised in 74 countries. In March 2007, the FDA approved lapatinib in combination with capecitabine for the treatment of patients with advanced or metastatic BC whose tumours overexpress HER2/ErbB2 and who have received prior therapy, including an anthracycline, a taxane and Herceptin (trastuzumab). In June 2008, the EC granted a conditional marketing authorisation for lapatinib in all 27 EU member states.
According to Espicom Business Intelligence, sales of lapatinib in BC could reach US$1,732 million by 2014; however, longer-term sales will be partially impacted by the launch of other targeted therapies, such as Roche’s pertuzumab, which is anticipated to be launched in 2012. Even if the drug is approved for first-line treatment, it may still not reach patients in some countries. GSK has recently stated that it is to appeal the UK's National Institute for Health and Clinical Excellence (NICE) decision in March to recommend against funding lapatinib, in combination with capecitabine, for women with advanced BC. If successful, the appeal will enable the NHS to offer a similar level of access to lapatinib as other EU countries where it has been granted funding, which incclude Slovenia, Slovakia, France, Spain, Germany, Italy and Ireland.
Although NICE acknowledged that lapatinib is an effective treatment for eligible women, it was rejected on the grounds that it was not a cost-effective use of NHS resources. This decision was reached despite GSK offering a patient access programme whereby the cost of up to 12 weeks' treatment would be paid by the company. GSK's analysis suggests that the cost-effectiveness of lapatinib in the context of the patient access programme (sensitive to the proportion of trastuzumab used in clinical practice) demonstrated a cost per QALY gain for lapatinib of just over £16,000 versus the usual care given to these patients, which includes standard chemotherapy and trastuzumab regimens.
Matthew Dennis - Editor, Cancer Drug News
The submissions are based on results from the recent EGF30008 study, which evaluated lapatinib plus Novartis' aromatase inhibitor, Femara (letrozole), in women with hormone receptor-positive metastatic BC that may or may not overexpress the HER2-positive receptor. Results from the study showed that women experienced a 5.2 month increase in median progression-free survival when treated with lapatinib+letrozole, compared to those treated with letrozole alone. Results from the intent-to-treat group showed that lapatinib+letrozole provided an additional 1.1 month before disease progression, compared to letrozole treatment alone.
Lapatinib, in combination with capecitabine, is currently authorised in 74 countries. In March 2007, the FDA approved lapatinib in combination with capecitabine for the treatment of patients with advanced or metastatic BC whose tumours overexpress HER2/ErbB2 and who have received prior therapy, including an anthracycline, a taxane and Herceptin (trastuzumab). In June 2008, the EC granted a conditional marketing authorisation for lapatinib in all 27 EU member states.
According to Espicom Business Intelligence, sales of lapatinib in BC could reach US$1,732 million by 2014; however, longer-term sales will be partially impacted by the launch of other targeted therapies, such as Roche’s pertuzumab, which is anticipated to be launched in 2012. Even if the drug is approved for first-line treatment, it may still not reach patients in some countries. GSK has recently stated that it is to appeal the UK's National Institute for Health and Clinical Excellence (NICE) decision in March to recommend against funding lapatinib, in combination with capecitabine, for women with advanced BC. If successful, the appeal will enable the NHS to offer a similar level of access to lapatinib as other EU countries where it has been granted funding, which incclude Slovenia, Slovakia, France, Spain, Germany, Italy and Ireland.
Although NICE acknowledged that lapatinib is an effective treatment for eligible women, it was rejected on the grounds that it was not a cost-effective use of NHS resources. This decision was reached despite GSK offering a patient access programme whereby the cost of up to 12 weeks' treatment would be paid by the company. GSK's analysis suggests that the cost-effectiveness of lapatinib in the context of the patient access programme (sensitive to the proportion of trastuzumab used in clinical practice) demonstrated a cost per QALY gain for lapatinib of just over £16,000 versus the usual care given to these patients, which includes standard chemotherapy and trastuzumab regimens.
Matthew Dennis - Editor, Cancer Drug News
Tuesday, October 14, 2008
NICE set to block Tyverb's use on NHS
A draft recommendation by the UK's National Institute for Health and Clinical Excellence (NICE) in a second technology appraisal consultation document (ACD) has indicated that GlaxoSmithKline's Tyverb (lapatinib; known as Tykerb in the US and certain other markets) should not be used in the NHS, except in clinical trials. The oral drug is currently approved in the EU in combination with Xeloda (capecitabine) for the treatment of women with ErbB2 (HER2)-positive advanced breast cancer (BC), whose disease has stopped responding to Herceptin (trastuzumab). The draft guidance comes despite GSK proposing a patient access programme (PAP), where it would bear the cost of the drug for the first 12 weeks of treatment.
Lapatinib, in combination with capecitabine, is the only treatment option that is licensed for use in patients with this aggressive form of advanced BC, who have limited treatment options remaining if their cancer has continued to grow despite treatment with standard chemotherapies and trastuzumab for advanced disease. In a pivotal trial that led to its EU licence, lapatinib+capecitabine significantly increased the time-to-progression (TTP) for patients with ErbB2-positive BC compared with capecitabine alone. In its draft guidance, NICE acknowledged that lapatinib is a clinically-effective option and noted that lapatinib+capecitabine was associated with improved TTP and progression-free survival.
In recognition that the first ACD from NICE did not consider lapatinib to be cost effective in treating this patient population, GSK proposed a PAP, where the company would bear the cost of lapatinib for all eligible patients, for up to the first 12 weeks of treatment. The NHS would commence payment only for those patients who continue to receive clinical benefit beyond 12 weeks. Criteria for continuation of therapy beyond 12 weeks would be determined by the individual person's clinician, based on reduction in lesion size, presence of stable disease or improvement in other response criteria such as symptoms. This programme was designed to provide access to all eligible patients and deliver cost-effectiveness at a threshold that should have been acceptable to NICE.
The cost effectiveness of lapatinib+capecitabine was supported by a comparison to trastuzumab-containing regimens and capecitabine alone, representing the established treatment regimens in NHS clinical practice. Whilst NICE accepted that trastuzumab is widely used following progression of the disease, the Committee suggested that it was unlikely to be cost effective, and therefore did not accept trastuzumab as a valid comparator. According to GSK, the way in which the decision was made makes it very difficult to ever demonstrate the cost effectiveness of lapatinib in this patient population, even in light of the proposed PAP.
Following the ACD, GSK will continue to work with NICE to demonstrate the cost effectiveness of lapatinib in all eligible patients by seeking to validate trastuzumab as a legitimate comparator. The next meeting will be held on 19th November, however, it looks as though NICE will stick with its current draft guidance and recommend against funding lapatinib on the NHS.
Matthew Dennis - Editor, Cancer Drug News
Lapatinib, in combination with capecitabine, is the only treatment option that is licensed for use in patients with this aggressive form of advanced BC, who have limited treatment options remaining if their cancer has continued to grow despite treatment with standard chemotherapies and trastuzumab for advanced disease. In a pivotal trial that led to its EU licence, lapatinib+capecitabine significantly increased the time-to-progression (TTP) for patients with ErbB2-positive BC compared with capecitabine alone. In its draft guidance, NICE acknowledged that lapatinib is a clinically-effective option and noted that lapatinib+capecitabine was associated with improved TTP and progression-free survival.
In recognition that the first ACD from NICE did not consider lapatinib to be cost effective in treating this patient population, GSK proposed a PAP, where the company would bear the cost of lapatinib for all eligible patients, for up to the first 12 weeks of treatment. The NHS would commence payment only for those patients who continue to receive clinical benefit beyond 12 weeks. Criteria for continuation of therapy beyond 12 weeks would be determined by the individual person's clinician, based on reduction in lesion size, presence of stable disease or improvement in other response criteria such as symptoms. This programme was designed to provide access to all eligible patients and deliver cost-effectiveness at a threshold that should have been acceptable to NICE.
The cost effectiveness of lapatinib+capecitabine was supported by a comparison to trastuzumab-containing regimens and capecitabine alone, representing the established treatment regimens in NHS clinical practice. Whilst NICE accepted that trastuzumab is widely used following progression of the disease, the Committee suggested that it was unlikely to be cost effective, and therefore did not accept trastuzumab as a valid comparator. According to GSK, the way in which the decision was made makes it very difficult to ever demonstrate the cost effectiveness of lapatinib in this patient population, even in light of the proposed PAP.
Following the ACD, GSK will continue to work with NICE to demonstrate the cost effectiveness of lapatinib in all eligible patients by seeking to validate trastuzumab as a legitimate comparator. The next meeting will be held on 19th November, however, it looks as though NICE will stick with its current draft guidance and recommend against funding lapatinib on the NHS.
Matthew Dennis - Editor, Cancer Drug News
Wednesday, May 21, 2008
Targeted combination effective against metastatic BC
GlaxoSmithKline has reported positive data from the first randomised, multi-centre, open-label Phase III trial of the combination of two targeted agents, Tykerb (known as Tyverb in Europe; lapatinib) and Herceptin (trastuzumab), in women with HER2-positive metastatic breast cancer (BC).
In the study, 296 patients with HER2 (ErbB2)-positive BC who had documented progression on trastuzumab treatment in the metastatic setting were eligible to be randomised to receive lapatinib (1,000mg) plus trastuzumab (2mg/kg weekly after 4mg/kg loading dose) or lapatinib alone (1,500mg). Patients were heavily pretreated and had received a median of six prior anticancer regimens. Patients had received a median of three prior lines of trastuzumab. The primary endpoint of the study was progression-free survival (PFS), and secondary endpoints included clinical benefit rate, response rate and overall survival. If patients progressed on the lapatinib monotherapy arm after four weeks of therapy, they could cross over to receive the combination of lapatinib+trastuzumab.
Despite receiving multiple prior lines of anticancer therapy, patients who received lapatinib plus trastuzumab in this study experienced:
In the study, 296 patients with HER2 (ErbB2)-positive BC who had documented progression on trastuzumab treatment in the metastatic setting were eligible to be randomised to receive lapatinib (1,000mg) plus trastuzumab (2mg/kg weekly after 4mg/kg loading dose) or lapatinib alone (1,500mg). Patients were heavily pretreated and had received a median of six prior anticancer regimens. Patients had received a median of three prior lines of trastuzumab. The primary endpoint of the study was progression-free survival (PFS), and secondary endpoints included clinical benefit rate, response rate and overall survival. If patients progressed on the lapatinib monotherapy arm after four weeks of therapy, they could cross over to receive the combination of lapatinib+trastuzumab.
Despite receiving multiple prior lines of anticancer therapy, patients who received lapatinib plus trastuzumab in this study experienced:
- a statistically significant increase in median PFS versus lapatinib alone (12 vs 8.1 weeks);
a 27 per cent reduction in the risk of disease progression (hazard ratio [HR]=0.73; p=0.008); - a response rate of 10.3 versus 6.9 per cent;
double the overall clinical benefit rate versus lapatinib alone (24.7 vs 12.4 per cent; p=0.01); and - a trend in improved overall survival (HR=0.75; p=0.106).
The study also demonstrated the activity of lapatinib as a single agent in this patient population, with patients on this arm achieving a median PFS of 8.1 weeks and an overall clinical benefit rate of 12.4 per cent.
Adverse events were similar in both arms, with Grade 1/2 diarrhoea significantly higher in the lapatinib+trastuzumab arm (53 vs 41 per cent; p=0.03). Two patients in the combination arm and one patient in the lapatinib monotherapy arm experienced symptomatic decreases in left ventricle ejection fracture (LVEF); one patient in the lapatinib+trastuzumab arm died due to a pulmonary thromboembolism with progressive malignant pleural effusions; two patients with LVEF decrease later recovered. Isolated cases of asymptomatic transient decreases in LVEF were noted in both treatment arms.
Both treatments target the HER2 protein but work in different ways. Trastuzumab attaches to the outside of the HER2 protein, while lapatinib enters the cell to block signals from the HER2 protein for the cancer to grow. The clinical synergy of lapatinib and trastuzumab confirms previous observational findings in preclinical studies and previously reported data from a Phase I study. These latest findings confirm the rationale for further research of this combination in earlier lines of therapy in the metastatic setting and in early-stage disease. Additional analysis is under way to explore the benefit that lapatinib plus trastuzumab can offer to less heavily-pretreated patients.
Matthew Dennis - Editor, Cancer Drug News
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