Wow, my blog on abiraterone in advanced prostate cancer got picked up last night by TopUSAsites for prostate cancer.
It looks like the drug is going to be a hot topic for a while, but caution against the hype is advised until we see whether reduction in PSA and tumour shrinkage actually translates to what really matters to patients – improved survival and better quality of life.
What say you?
The UK has recently approved a second vaccine that protects against HPV called Cervarix from GSK, in addition to Gardasil from Merck. Both vaccines protect against HPV, but Gardasil also protects against gentical warts, which Cervarix does not.
Male with genital warts – image courtesy of Wikipedia
The wholesale price for the two is exactly the same, £80.50, and the formal list price is also comparable at £240 per vaccination. Other European countries appear to have chosen Gardasil, for it’s extra protective effects. Genital warts are, of course, far more common than cervical cancer in Western Europe. Most women over 40 receive a regular annual Pap smear to screen for HPV and cervical cancer, hence the low rates compared to Latin America and Africa, where the smear test is considerably less common.
Guess which vaccine the NHS chose in it’s wisdom? Yes, Cervarix. Any parent wanting to innoculate their daughter with Gardasil will therefore have to get it on private health plans at a much greater cost.
Meanwhile, although a small number of boys were included in the trial, there were insufficent numbers to gain approval for use in the male population. If you are going to reduce the spread of genital warts and HPV in the population, it makes sense to innoculate both surely?
ImClone announced that late-stage study data showed that first-line treatment with Erbitux (cetuximab) plus standard chemotherapy significantly increased overall survival by about five weeks in patients with advanced non-small cell lung cancer (NSCLC), compared with chemotherapy alone. The results were presented at the American Society of Clinical Oncology (ASCO) meeting this weekend.
To put things in context, the American Cancer Society estimates that in the United States, more than 215,000 people will be diagnosed with lung cancer in 2008, which accounts for about 15 percent of all cancer diagnoses. Approximately 87 percent of these patients will be diagnosed with NSCLC, with many being diagnosed with locally advanced or metastatic disease. Lung cancer is the leading cause of cancer-related death in men and women, with more than 161,000 deaths expected to occur in 2008 – accounting for about 29 percent of all cancer deaths. In 2008, it is estimated that more Americans will die from lung cancer than breast, prostate, and colorectal cancers combined. Studies showing a significant improvement in survival will therefore impact the course of disease and affect large numbers of patients.
The randomised FLEX study involved 1125 patients with advanced non-small cell lung cancer (NSCLC) who had not previously received chemotherapy. The data demonstrated that those who received ImClone announced that Erbitux combined with chemotherapy resulted in a median overall survival of 11.3 months, compared with 10.1 months for chemotherapy alone, a significant difference. The findings also showed that tumours shrank in 36.3 percent of patients who received the Erbitux regimen, compared with 29.2 percent of patients who only received standard chemotherapy.
It is unlikely that the findings are impressive enough to significantly affect the position of Genentech’s Avastin for patients with lung cancer who can be treated with the product in the short term. However, doctors treating patients with NSCLC who cannot take Avastin may opt to prescribe Erbitux, which could lead to an additional $700 million in annual sales in the US.
Overall, probably one in five patients or less get Avastin, so there’s a huge opportunity outside of that in the long run, and the data are very competitive. Erbitux is expected to be filed for expanded US approval in NSCLC in the second half of this year, and the new indication could be added to the label by mid-2009. If approved, this will open new first-line treatment options for patients with non-small cell lung cancer regardless of histological subtypes, and potentially set a new standard in the first-line treatment of this disease.
Today I was at the ophthalmologists office getting my eyes tested for some new glasses. The technician and I were chatting convivially about the pros and cons of Avastin versus Lucentis for wet age-related macular degeneration (AMD).
Later, while looking at the National Institutes of Health (NIH) site on the internet, I noticed they have finally started an independent trial that is designed to show how the two drugs stack up against each other. Both inhibit Vascular Endothelial Growth Factor (VEGF) but have different approved uses and indications.
Lucentis has been FDA-approved for use against wet AMD. Avastin isn’t,it’s approved for treatment of cancers such as colorectal carcinoma. Ophthalmologists and retinal surgeons have, however, commonly used it off-label, saying it’s almost as effective as Lucentis, if not as effective. And Avastin also costs much less, i.e. $50 rather than $2,000. The challenge was that Avastin needed to be compounded by pharmacies and last year Genentech moved to restrict sales of Avastin to those pharmacies who were compounding Avastin for ophthalmology use, stating that there was a risk of microbial contamination from compounding and the FDA were concerned about the re-packaging.
The NIH decided to take matters into its own hands and perform a trial to answer the question. Time will tell. If the trial shows no difference between the two, expect Avastin to cannibalise sales of Lucentis and insurers/payers to exert their muscle in favour of the cheaper alternative.
Last week, AstraZeneca announced the submission of a marketing authorisation application to the European Medicines Agency (EMEA) for its oral anti-cancer drug, gefitinib (IRESSA™) as a treatment for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) in patients who have been pre-treated with platinum-containing chemotherapy.
The application was based on data from the Phase III INTEREST study, which showed that patients with pre-treated advanced NSCLC who received gefitinib had non-inferior overall survival to those treated with intravenous chemotherapy with a taxane (docetaxel). Gefitinib apparently had a more favourable tolerability profile than docetaxel and significantly more patients receiving gefitinib had an improvement in quality of life. In other words, they are attempting to do what Lilly did with Alimta in second-line treatment of NSCLC with their comparative trial against docetaxel.
This is the first time an Epidermal Growth Factor Receptor – Tyrosine Kinase Inhibitor (EGFR-TKI) has proven non-inferiority for overall survival relative to chemotherapy in patients with pre-treated advanced NSCLC. If the EU approve the therapy, it will be interesting to see how the US view the data.
The announcement represents a return to the spotlight for gefitinib, which had first-quarter sales of $58 million and is available in 36 countries. It was previously touted as a potential blockbuster, but those hopes collapsed in 2004 when results from a 1,700-patient study in people with advanced NSCLC who had failed previous chemotherapy, revealed that at the end of one year, just 27% of the Iressa group were still alive compared to 21% of placebo, a non-significant result.
AstraZeneca was allowed to keep the drug on the market in the USA, but its use was heavily restricted and no new patients were allowed access to the therapy unless they were taking part in a clinical trial. The company withdrew its application to market Iressa in Europe shortly after.
The National Institute for Health and Clinical Excellence (NICE) have announced their decision not to recommend the use of Tarceva (erlotinib) for the treatment of locally-advanced or metastatic non-small-cell lung cancer (NSCLC) in the National Health Service (NHS) in England and Wales.
NICE’s Final Appraisal Determination (FAD) on Tarceva last week concluded that the drug “could not be considered a cost-effective use of NHS resources” when compared with either docetaxel or best supportive care. People currently receiving Tarceva “should have the option to continue therapy until they and their clinicians consider it appropriate to stop.” The Appraisal Committee that assessed Tarceva, also indicated that it awaits the results of ongoing trials comparing the drug with docetaxel, and recommends further research into subgroups for whom Tarceva “may provide greater benefit.”
This is an interesting perspective, given the US approach of screening patients who are EGFR-positive with K-Ras mutations who would be suitable for Tarceva therapy. Taking a break from chemotherapy may also prolong survival across multiple lines of therapy. Docetaxel is well known for its severe myelosuppressive effects that cause cancer patients to feel exhausted and beaten up. Tarceva, a small molecule targeted therapy has been shown to be superior to placebo in efficacy, survival and quality of life, so the decision is somewhat surprising clinically.
To put it in context, chemotherapy is only somewhat effective for patients with advanced NSCLC, although there is some evidence for a benefit in terms of survival and symptom relief. Response times to treatment are brief, and the median time to cancer progression is three to five months. In patients who initially received platinum-based chemotherapy for NSCLC, docetaxel offers the chance to improve survival for those with disease progression. Data suggests, however, that third-line chemotherapy is similar to supportive care in terms of survival, and the response rates to such therapy are bleak.
A randomized, placebo-controlled, double-blind trial was recently conducted to determine whether the EGFR inhibitor erlotinib prolongs survival in non–small-cell lung cancer after the failure of first-line or second-line chemotherapy. It clearly demonstrated that erlotinib prolonged survival.
Eligible patients had stage IIIB or IV NSCLC, with performance status of between 0 and 3, and had undergone one or two prior rounds of chemotherapy. In a 2:1 ratio, 731 patients were randomized to receive either 150 mg of oral erlotinib daily or placebo, and they were stratified by center, performance status, response to prior chemotherapy, number of prior rounds of chemotherapy, and prior platinum-based therapy. Median age was 61.4 years, 49% had undergone two prior rounds of chemotherapy, and 93% had received platinum-based chemotherapy. Response rate was 8.9% with erlotinib and less than 1% with placebo (P < .001), with respective median durations of response being 7.9 and 3.7 months.
After adjustment for stratification categories, progression-free survival was 2.2 months with erlotinib and 1.8 months with placebo (hazard ratio [HR], 0.61; P < .001). Overall survival was 6.7 months with erlotinib and 4.7 months with placebo (HR, 0.70; P < .001). Only 5% of patients discontinued erlotinib because of toxic side effects.
The positive clinical data has been available in the public domain for a while now. This appears to be a financial decision rather than a clinical one. Given that the drug budget is a very small part of the overall NHS budget, one wonders why they don’t attack the overinflated administrative staff budget with the same verve and vigour that they do with the relatively much smaller drug budgets.
