Wednesday, October 28, 2009

2,000 UK women denied BC treatment

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

Thursday, October 22, 2009

Cancer proven to pass from mother to baby

A rare case of a mother and her infant developing the exact same cancer has allowed an international team of researchers from the Institute of Cancer Research (ICR), to solve a puzzle that has perplexed scientists and clinicians for a century. The scientists, with funding from Leukaemia Research, investigated a situation in which leukaemic cells appeared to have defied accepted theories of biology and spread through the womb from a Japanese woman to her daughter.

Approximately 30 previously-known cases of a mother and infant appearing to share the same cancer had already raised suspicions that such spread was possible. However, there was no genetic evidence to support this theory, and investigators did not know how it could occur as the baby's immune system should have recognised and destroyed any invasive cancer cells that were of maternal, and therefore foreign, origin. In a study, published in the 12th October online edition of PNAS (10.1073/pnas.0904658106), the scientists used advanced genetic fingerprinting to prove for the first time that the infant's leukaemic cells were unquestionably of maternal origin.

The researchers found that both patients' leukaemic cells carried the identical mutated cancer gene, Bcr-Abl1, but the infant had not inherited this gene. This meant that the child could not have developed this type of leukaemia in isolation. To investigate how the cells could have crossed the placental barrier and survived in the offspring, the scientists looked for evidence of some form of immunological acceptance or tolerance of the foreign cells by the foetus. They examined the genes of the cancer cells in the infant and found some DNA missing in the region that controls expression of the major histocompatibility locus. This was significant because HLA molecules primarily distinguish one individual, and his or her cells, from another, so the absence of these molecules on the cancer cells meant that the infant's immune system would not have recognised that they were foreign.

It appears that in this and, the scientists presume, other cases, the maternal cancer cells did cross the placenta into the developing foetus and succeeded in implanting because they were invisible to the immune system. Dr David Grant, Scientific Director at Leukaemia Research, commented: "the important message from this fascinating piece of research is that leukaemia cells can be destroyed by the immune system. Harnessing the power of the immune system to first cure and then protect patients from leukaemia is one of our priority areas of research."

According to Professor Peter Johnson, Cancer Research UK's Chief Clinician, this finding provides further evidence that cancers are generated more often than first thought. A large part of cancer research is on cancer immunity; scientists have known for quite some time that people with deficient immune systems, perhaps because of HIV or immunosuppression after organ transplants, are much more prone to certain types of cancer. The real challenge for researchers now is to work out how to invigorate the immune system so it recognises cancer cells.

Alice Rossiter
Cancer Drug News Editor

Thursday, October 15, 2009

Vaccination and testing for HPV could eradicate CC

According to a cervical cancer (CC) screening expert, Professor Jack Cuzick, from Cancer Research UK, the disease could be eradicated within the next 50 years if countries implement national screening programmes based on the detection of the human papillomavirus (HPV). Cuzick told the recent joint 15th ECCO and 34th ESMO Congress that while the current HPV vaccines protect against two cancer-causing strains of the HPV virus, soon there would be vaccines available that protect against nine types. If vaccination were to be combined with HPV screening, which is much more sensitive than the currently used Pap smear test, then eventually the cancer would disappear in those countries that had successfully implemented national programmes. However, this would require political will and effort at both national and European levels.

The current vaccine holds the promise of eradicating approximately 70 to 75 per cent of CC (caused by HPV types 16 and 18), and there appears to be some additional cross protection amongst types that are closely related to 16 or 18, in particular 31, 45 and a part of 33. There are new vaccines being planned that will vaccinate against nine types; if they are successful, there should be no need to screen women that have been vaccinated at all.

The Pap test relies on subjective assessments by people examining the cells in the smear with a microscope and therefore is open to human error. Cuzick believes that such errors will increase as the proportions of smears with affected cells decline due to increasing numbers of women having been vaccinated. In contrast, the HPV test is almost completely automated, is designed to detect the virus in the smear rather than relying on visual examination and therefore is much less likely to be affected by human error. Cuzick commented: "there's overwhelming evidence that HPV screening is more effective than the Pap smear test, which misses about a third to a half of all high-grade lesions". However, Cuzick warned that the EU and national governments should take the initiative in discussions on implementing screening and vaccination programmes, rather than leaving it to pharmaceutical companies to lead the debate.

During the last fortnight, much data have been reported in relation to CC drug and vaccine trials. Of particular note, results from the PATRICIA (PApilloma TRIal Cervical cancer In young Adults or HPV 008) study showed that GlaxoSmithKline's Cervarix is highly effective at protecting against the two most common CC-causing HPV types, 16 and 18. Furthermore, Cervarix demonstrated efficacy against cervical intraepithelial neoplasia 2+ lesions associated with 12 additional HPV types beyond 16 and 18, including HPV 31, 33 and 45.

In addition, Phase I trial results of ADXS11-001 have shown 36-month survival in three of the 13 evaluable patients treated with Advaxis' therapeutic cancer vaccine, which treats women who have already developed CC as a result of HPV infection, indicating the possibility of persistent immune protection. Further, interim safety and immunogenicity data from a Phase I trial of Inovio Biomedical's VGX-3100 showed that the therapeutic CC vaccine was generally safe and well tolerated, plus it achieved significant cellular and humoral immune responses at the lowest dose administered. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of HPV types 16 and 18.

Alice Rossiter - Cancer Drug News Editor