Study showed Alimta improved survival in certain types of Non-Small Cell Lung Cancer

The type of non-small cell lung cancer (NSCLC) patients have may now influence their treatment regimen and, in turn, survival outcome according to the results of a major study published online in the Journal of Clinical Oncology.

NSCLC is the most common type of lung cancer and represents 85 to 90 percent of all lung cancers. According to the World Health Organization (WHO) Cancer Report, lung cancer is the world's most common cancer and the leading cause of cancer death for both men and women. More than 1 million people die from lung cancer each year.

NSCLC is defined as a group of histologies i.e. tumour types differentiated by cellular structure. The most common NSCLC histology types are squamous (or epidermoid) carcinoma, adenocarcinoma, and large cell carcinoma. These histologies are often classified together because, to date, approaches to diagnosis, staging, prognosis, and treatment have been similar.

The study, the largest Phase III clinical trial in the first-line NSCLC setting, evaluated ALIMTA® (pemetrexed for injection) plus cisplatin versus GEMZAR® (gemcitabine HCl for injection) plus cisplatin, a standard of treatment in this setting. The trial met its primary endpoint of non-inferiority relative to overall survival.

Additionally, in a pre-planned histological analysis, patients with either adenocarcinoma or large-cell carcinoma had a statistically superior and clinically relevant improvement in overall survival when treated with the pemetrexed regimen in the first-line setting.

In comparison, patients with squamous cell histology were found to have a more favorable overall survival when treated with the gemcitabine regimen.

The overall survival of patients treated with either the pemetrexed regimen or gemcitabine regimen was found to be non-inferior, with a median survival of 10.3 months. However, when researchers reviewed survival rates according to histological analysis, it was found that patients with adenocarcinoma achieved 12.6 months of overall median survival when treated with the pemetrexed regimen compared to 10.9 months for those treated with the gemcitabine regimen. Patients with large cell carcinoma who were treated with the pemetrexed regimen achieved 10.4 months of overall median survival versus 6.7 months for those treated with the gemcitabine regimen. Both findings are statistically significant.

Patients with squamous cell histology were found to have a more favorable rate of survival when treated with the gemcitabine regimen, achieving 10.8 months of median survival, compared to the 9.4 months for those treated with the pemetrexed regimen. This finding was statistically significant.

The Phase III, randomized study compared the overall survival between pemetrexed+cisplatin versus gemcitabine+cisplatin in chemonaive patients (1,725) with stage IIIB or IV NSCLC who also exhibited a performance status of 0-1. Patients on the pemetrexed arm (862) were treated with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day one every three weeks for up to six cycles. Patients on the gemcitabine arm (863) were treated with cisplatin (75 mg/m2) on day one and gemcitabine (1250 mg/m2) on days one and eight every three weeks for up to six cycles.

Hematologic grade 3/4 drug-related toxicities including neutropenia, anemia and thrombocytopenia were significantly lower for patients on the pemetrexed arm. Drug-related grade 3/4 febrile neutropenia and alopecia (all grades) were also significantly less on the pemetrexed arm. Drug-related grade 3/4 nausea was more common in patients treated with pemetrexed. Safety data by histology was generally consistent with the overall safety results.

Overall, patients with adenocarcinoma or large cell carcinoma histologies achieved improvement in overall survival when treated with Alimta (pemetrexed) based regimens.

While non-small cell lung cancer has typically been treated as one disease, this study confirms that histology, or tumour type, can provide a clue as to which treatment regimen works best for a particular tumor type. It suggests that if we can select the therapy for better results, we are closer to improving outcomes for lung cancer.

Oncology: Renal cell cancer slowed by Novartis' RAD001

Nearly two-thirds of renal cell cancer patients taking Novartis AG's RAD001 (everolimus) had progression of their disease delayed by a year, a significantly better result than in those taking placebo. Everolimus may offer potential new treatment option for patients with advanced kidney cancer who have failed standard therapies. The study assessed patients whose cancer had worsened despite receiving approved treatments for renal cancer, such as Bayer AG's Nexavar or Pfizer Inc's Sutent, or both.

Amazingly, the disease did not progress for one year in 65 percent of patients taking the once-daily RAD001 tablet, compared to 37 percent in those taking placebo, according to detailed results from a late-stage trial, which was stopped early because it met its main target.

The drug works by blocking a protein known as mTOR and disrupts the growth, division and metabolism of cancer cells.

Full results of the trial are due to be presented in an oral session at ASCO later this month (Abstract #LBA5026: Saturday, May 31, 2008; 4:30 PM-4:45 PM CDT).

There were 410 patients in the trial, 272 taking RAD001 and 138 placebo. Novartis announced it intends to file the drug for regulatory approval later this year.

Market trends: cancer vs. ophthalmology drugs

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.

AZ and Iressa attempting a comeback in lung cancer?

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.

Does aspirin lower the risk of breast cancer?

A daily aspirin may give women modest protection against the most common type of breast cancer according to a study published in Breast Cancer Research. The finding reinforced earlier research indicating regular use of aspirin might reduce the risk of so-called estrogen receptor-positive breast cancer, which makes up about three quarters of breast cancer cases.

Estrogen receptor or ER-positive breast cancer is fueled by estrogen and aspirin may interfere with this hormone's activity. Researchers led by Gretchen Gierach of the National Cancer Institute, part of the National Institutes of Health, found that women who took aspirin daily cut their risk of developing this type of breast cancer by 16 percent.

The research involved about 127,000 women aged 51 to 72 from around the United States who were cancer-free when the study began. About 18 percent of the women were daily aspirin users. They were tracked for seven years and about 4,500 of them developed breast cancer.

The study did not find any relationship between aspirin and the less-common estrogen receptor-negative breast cancer. It also did not find any protective effect in women who took aspirin less than daily.

The study is the latest to suggest aspirin offers benefits beyond relieving headaches and body aches and reducing fevers. Aspirin is a common anti-inflammatory painkiller that can be used to relieve symptoms of arthritis and prevent second heart attacks and other ailments. Previous research has indicated it also may protect against colorectal cancer. It is possible that aspirin acts to reduce inflammation in cancer, which can trigger tumour growth.