Med BioGene Inc. (TSX VENTURE:MBI) today announced positive results from the current validation study of LungExpress DxTM undertaken by MBI and its collaborators at the University Health Network (Princess Margaret Hospital) in Toronto.

The study met its primary endpoint in confirming that the 15-gene expression-based assay underlying LungExpress DxTM is an independent prognostic marker in early-stage non-small-cell lung cancer (NSCLC) for identifying, more selectively than routine staging, patients with significantly different prognoses and may provide additional clinical value beyond standard measures of risk. MBI and UHN expect to submit for publication the detailed results of the study.

“Not all patients benefit from chemotherapy and not all patients require chemotherapy after surgery,” said Dr. Ming-Sound Tsao of the University Health Network. “Knowing that a patient has a genetic signature for a more aggressive cancer and that their chance of cure may be improved with chemotherapy gives patients and their doctors a clearer picture of the need for post-operative treatment.”

The study was performed in an independent set of tumour samples from 183 untreated stage I and II NSCLC patients (predominantly adenocarcinoma and squamous cell carcinoma) collected over a five-year period. To date, the prognostic utility of LungExpress DxTM has been validated in approximately 675 patient samples.

Based upon these positive results, MBI is continuing with its commercialization plans to make LungExpress DxTM available to physicians and patients initially in the United States in early 2010.

“We are very pleased with the positive findings from this important validation study,” said Erinn B. Broshko, Chief Executive Officer of MBI. “The results confirm the biological robustness of LungExpress DxTM and move us closer to introducing commercially the first multi-gene prognostic test for early-stage non-small-cell lung cancer.”

“This test may improve patient care by providing a clearer understanding of each patient’s risk of cancer recurrence after surgery, potentially resulting in better-informed, more appropriate treatment decisions. We are moving closer to the ultimate goal of personalized medicine,” said Dr. Frances A. Shepherd of the University Health Network.

About LungExpress DxTM

LungExpress DxTM is a proprietary 15-gene expression-based assay that classifies patients into high and low risk prognostic groups based upon the molecular profile of a particular patient’s tumour and is expected to be used in conjunction with existing clinical parameters to provide additional independent clinical value beyond standard measures of risk.

The original study presented at the 2008 Annual Meeting of the American Society of Clinical Oncology involving tumour samples collected prospectively from patients participating in an adjuvant chemotherapy (cisplatin / vinorelbine) clinical trial showed that those patients classified by LungExpress DxTM as high risk benefitted, and those classified as low risk did not benefit, from adjuvant chemotherapy following resection of their tumour.

Treatment of Early-Stage Non-Small-Cell Lung Cancer

Early-stage NSCLC patients are treated primarily by surgical removal of their tumours. Recent clinical trials have established that adjuvant chemotherapy, administered after tumour removal, significantly improves the survival of stage II patients, but does not significantly improve the survival of stage I patients. As a result, the American Society of Clinical Oncology and National Comprehensive Cancer Network recommend adjuvant chemotherapy for stage II patients but not for stage I patients.

However, 30% to 55% of stage I and II patients still die as a result of the disease, implying that patients diagnosed with the same stage of disease can have markedly different treatment responses and overall outcomes. Currently, tumor stage (determined by the size and location of the tumor, lymph node involvement and metastatic status) remains the strongest predictor of survival but fails to account for this difference in patient outcomes. LungExpress DxTM is expected to help address this critical issue.

Source
University Health Network and Princess Margaret Hospital

OSI Pharmaceuticals, Inc. (NASDAQ: OSIP) and Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG)(OTCQX: RHHBY), announced that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to one recommending against approval of the daily pill cancer has not progressed (grown or spread) following first-line treatment with platinum-based chemotherapy. The FDA is not bound by the recommendations of its advisory committees and the agency is expected to make a decision whether to approve Tarceva for this use by January 18, 2010.

“We are disappointed with the Committee’s recommendation and will work diligently to respond to the issues that arose today as quickly as possible,” said Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. “We continue to believe that having an oral, well-tolerated treatment option that can maintain the initial benefit from cytotoxic chemotherapy would be an important advance in treating advanced lung cancer and will explore further with regulatory agencies how best to pursue this outcome.”

“We continue to hope Tarceva may be an option that could help more people with advanced non-small cell lung cancer live longer without the disease getting worse,” said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. “We will work closely with OSI to carefully review and address the Committee’s comments.”

The ODAC recommendation was based on a review of data from the pivotal Phase III SATURN study which showed a statistically significant improvement in both progression-free survival (PFS) and overall survival (OS) with Tarceva compared to placebo in the NSCLC maintenance setting. There were no new or unexpected safety signals in the study and adverse events were consistent with those previously reported for Tarceva in NSCLC.

- People who received Tarceva had a 41 percent improvement in the likelihood of living without the disease getting worse (PFS, the primary endpoint) compared to placebo (hazard ratio=0.71, 29 percent reduction in the risk of cancer progression or death, p<0.0001; median PFS 12.3 weeks vs. 11.1 weeks).

- People whose tumors over-expressed the epidermal growth factor receptor (EGFR) as assessed by Immunohistochemistry (IHC) who received Tarceva had a 45 percent improvement in PFS compared to placebo (the co-primary endpoint; hazard ratio=0.69, 31 percent reduction in the risk of cancer progression or death, p<0.0001; median PFS 12.3 weeks vs. 11.1 weeks).

- OS, a key secondary endpoint, was also significantly improved by 23 percent with Tarceva compared to placebo (hazard ratio=0.81, 19 percent reduction in the risk of death, p=0.0088; median OS 12.0 months vs. 11.0 months).

- The most commonly reported adverse events in patients who received Tarceva were rash (49 percent) and diarrhea (20 percent). Grade 3 rash and diarrhea were experienced by six percent and two percent of patients, respectively. There were no cases of Grade 4 rash or diarrhea.

About SATURN

SATURN was an international, placebo-controlled, randomized, double-blind, Phase III study that enrolled 889 patients with advanced NSCLC at approximately 160 sites worldwide. Patients were treated with four cycles of standard first-line platinum-based chemotherapy and then randomized to Tarceva or placebo if the cancer did not progress. The co-primary endpoints were PFS in all patients and PFS in patients whose tumors over-expressed EGFR as assessed by IHC. PFS was defined as the length of time from randomization to disease progression or death from any cause. Secondary endpoints included OS, safety and an evaluation of exploratory biomarkers.

About Lung Cancer

According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States. In 2009, approximately 159,000 Americans will die from the disease. Most people are diagnosed with advanced stage disease and only 15 percent survive five years. NSCLC is the most common type of lung cancer.

About Tarceva

Tarceva is a once-a-day pill that targets the EGFR pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cancer cell, one of the critical growth factors in NSCLC and pancreatic cancer. Tarceva is indicated as a monotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed after one or more courses of chemotherapy. Tarceva is not intended to be used at the same time as chemotherapy for NSCLC.

In pancreatic cancer, Tarceva is indicated in combination with gemcitabine chemotherapy for the first-line treatment of patients with locally advanced pancreatic cancer, pancreatic cancer that cannot be surgically removed or pancreatic cancer that has spread to distant body organs.

Tarceva Safety

There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects (including deaths) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome. Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke. Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the NSCLC clinical study. Fatigue, rash, nausea, loss of appetite and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in the pancreatic cancer clinical study.

About OSI Pharmaceuticals

OSI Pharmaceuticals is committed to “shaping medicine and changing lives” by discovering, developing and commercializing high-quality, novel and differentiated targeted medicines designed to extend life and improve the quality of life for patients with cancer and diabetes/obesity. For additional information about OSI, please visit http://www.osip.com.

Source
Genentech

View drug information on Tarceva.

The European Medicines Agency has been formally notified by AstraZeneca of its decision to withdraw its application for a centralised marketing authorisation for the medicine Zactima (vandetinib), 100 mg film-coated tablets.

Zactima was expected to be used in combination with chemotherapy, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received prior anticancer therapy.

The application for the marketing authorisation for Zactima was submitted to the Agency on 30 June 2009. At the time of the withdrawal, it was under review by the Agency’s Committee for Medicinal Products for Human Use (CHMP).

In its official letter, the company stated that the withdrawal of the application was based on the preliminary comments from the Rapporteur and Co-Rapporteur, which indicate that at this point in time the Committee would be unlikely to conclude on a favourable benefit-risk balance for the product in the treatment of NSCLC in combination with chemotherapy.

More information about Zactima and the state of the scientific assessment at the time of withdrawal will be made available in a question-and-answer document. This document, together with the withdrawal letter from the company, will be published on the Agency’s website after the next CHMP meeting of 16-19 November 2009.

Notes

1. Withdrawal of an application does not prejudice the possibility of a company making a new application at a later stage.

Source
EMEA

ORLANDO, May 31 — In what may be another nail in the coffin of combination hormone replacement therapy, researchers here said the menopause treatment is linked to an increased risk of dying of non-small cell lung cancer.

• Explain to interested patients that the Women’s Health Initiative found that the risks of combined hormone therapy to treat menopause outweighs the benefits.
• Note that this study found another risk — the chance of dying was increased if a woman developed non-small cell lung cancer while using the hormones.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In findings from the landmark Women’s Health Initiative, using estrogen and progestin led to a 59% increase in the risk of death if a woman developed non-small cell lung cancer, according to Rowan Chlebowski, M.D., Ph.D., of Harbor-UCLA Medical Center in Los Angeles.

There was also a trend toward greater incidence of the disease among women using the drug combination but it did not reach statistical significance, Dr. Chlebowski said at the annual meeting of the American Society of Clinical Oncology.

“This is one of a series of problems, especially with cancer, that work against wide-spread use of estrogen and progestin,” Dr. Chlebowski said.

But despite those earlier problems — increased risk of stroke, blood clots and breast cancer — many postmenopausal women are still using the combined hormone therapy, Dr. Chlebowski said.

He said between 25 and 30 million prescriptions are written every year and 15% of postmenopausal women still use the combination.

The Women’s Health Initiative study of combined hormone therapy enrolled 16,608 postmenopausal women ages 50 through 79 and randomized them to get placebo or the two hormones.

The study was stopped early when it became obvious that a range of harms outweighed the benefits, Dr. Chlebowski said.

As the researchers followed the participants, they noticed a significant increase in both fatal and non-fatal malignancies among those who took the hormones.

To try to explain the increase, they looked at the effect of the hormones on lung cancer, he said.

For small cell lung cancer, there was no difference in incidence or mortality between the arms of the study, Dr. Chlebowski said.

But for non-small cell lung cancer, analysis showed:

• A significant increase in the risk of dying if a woman taking the hormones developed cancer. The hazard ratio was 1.59, with a 95% confidence interval from 1.03 to 2.46, which was significant at P=0.04.
• Median survival of 9.4 months in the hormone arm, compared with 16.1 among women who got the disease in the placebo arm.
• A trend to more cases of the disease in the hormone arm. The hazard ratio was 1.28, but the confidence interval crossed unity.

All told, there were 67 deaths among the 8,052 women on hormones and 37 among the 7,678 women in the placebo group, Dr. Chlebowski said.

He added that, although smoking behavior was balanced between the study arms, smoking and taking the hormones led to an increase in the risk of death from the disease.

About one in 100 current smokers in the study had an avoidable cancer death associated with the combined hormone therapy, he said.

“Women almost certainly shouldn’t be using both combined hormone therapy and tobacco,” he said.

The finding is “a bit in contrast to the majority of case-control studies, where you see either no difference or a reduced risk,” said Bruce Johnson, M.D., of the Dana-Farber Cancer Institute, who was not part of the study.

“This is likely more accurate,” he said, “since this is controlled in a prospective randomized study.”

The study was supported by the NIH. The researchers reported financial links with Amgen, AstraZeneca, Eli Lilly, Novartis, and Wyeth. Dr. Johnson reported financial links with Genzyme, Boston Scientific, Celgene, and Johnson and Johnson.

Primary source: Journal of Clinical Oncology

Source reference:

Chlebowski RT et al. “Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women’s Health Initiative randomized clinical trial” J Clin Oncol 2009; 27(15S): Abstract CRA1500.

The Journal of Clinical Oncology (DOI: 10.1200/JCO.2008.20.2515) releases an article covering Active Biotech’s (NASDAQ OMX Nordic: ACTI) cancer project ANYARA, where ANYARA was studied both as a single agent and in combination with an established tumor therapy - docetaxel (Taxotere®) - in patients with advanced cancer.

Two parallel Phase I studies1) were performed, one monotherapy study (including 39 patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC) or renal cell cancer (RCC)) with ANYARA and one study in combination with docetaxel (13 patients with NSCLC), in order to assess the safety, tolerability and pharmacology of ANYARA.

The results showed that ANYARA was well tolerated both as monotherapy and in combination with docetaxel.

ANYARA showed immunological activity including systemic increase in inflammatory cytokines, selective expansion of ANYARA reactive T-cells and induction of tumor infiltrating T-cells. Anti-tumor activity was assessed and in the mono study fourteen patients (36%) had Stable Disease (SD) after two months. In the combo study the best overall response was confirmed Partial Response (a tumor reduction of at least 30 percent), for 2 patients (15%) and SD for 5 patients (38%).

ANYARA is presently in development primarily for the treatment of renal cell cancer. A pivotal phase III study, which has completed enrollment of over 500 patients, is currently ongoing.

Active Biotech AB (publ)

Tomas Leanderson
President & CEO

1) Previously presented in summary in press releases: December 13, 2006 “Active Biotech’s Novel Cancer Treatment ANYARA Shows Pharmacological Proof of Concept after Successful Phase I Studies” and October 24, 2007 “Active Biotech’s Cancer Project ANYARA Proven Safe in Combination with Taxotere®”, now detailed in JCO.

About ANYARA

ANYARA is a TTS (Tumor Targeting Superantigens) compound that makes the treatment of cancer tumor-specific. The development of ANYARA is mainly focused on renal cell cancer. Positive data was reported in connection with the interim analysis in Phase II/III and from clinical Phase I trials in lung cancer, renal cell cancer and pancreatic cancer. The median survival of 26.2 months observed for patients with advanced renal cancer and treated with ANYARA is twice the expected length. ANYARA has been granted orphan-drug status by the EMEA for the indication renal cancer. Information concerning the ongoing clinical trial is available at http://www.activebiotech.com and http://www.clinicaltrials.gov.

Source
Active Biotech

View drug information on Taxotere.

ORLANDO, June 1 — A two-drug maintenance regimen delayed recurrence of advanced non-small cell lung cancer better than a single drug, a researcher said here.

• Explain to patients that therapy for advanced non-small cell lung cancer now may include the monoclonal antibody bevacizumab (Avastin), which is used during initial chemotherapy and as maintenance treatment after the chemo is finished.
• Note that this study examined the effect of adding a second drug to the maintenance regimen and found somewhat promising results.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The drugs — bevacizumab (Avastin) and erlotinib (Tarceva) — were compared to bevacizumab plus placebo after the completion of standard chemotherapy, according to Vincent Miller, M.D., of Memorial Sloan-Kettering Cancer Center in New York City.

The delay — while statistically significant at P=0.001 — was not startlingly large. Patients getting bevacizumab and placebo had a median progression-free survival of 3.75 months, compared with 4.76 for those getting both drugs. But the results were promising, he told colleagues at the American Society of Clinical Oncology meeting here.

Bevacizumab is already a major component of therapy for patients with advanced disease, Dr. Miller said.

The new findings come from the so-called ATLAS trial, which enrolled 1,160 patients with locally advanced, recurrent, or metastatic non-small cell lung cancer.

After four cycles of first-line chemotherapy (which included bevacizumab), the 769 patients who had not progressed were randomized to one of the two maintenance therapy regimens.

Analysis showed “we can delay progression with the addition of a targeted agent,” Dr. Miller said.

Although the delay itself was not long, Dr. Miller said median progression-free survival might not tell the whole story. He pointed to the hazard ratio for progression, which was 0.77 in favor of the pair of drugs. (95% CI 0.59 to 0.88.)

In addition, he said, the rate of progression-free survival at various times during treatment will be important.

For example, he said, at three months, 53.4% of single-drug patients were still free of disease, compared with 67.7% of those getting the two drugs.

At six months, the comparable figures were 28.4% and 40.3%, he said.

Dr. Miller said that, in the long run, the two-drug strategy might be reserved for subsets of patients.

“My general feeling is that the strategy will not be employed in all patients, but in perhaps in select patients, say, who remained symptomatic after their initial therapy,” he said.

One advantage of both drugs is that they can be used extensively without building up side effects, said Bruce Johnson, M.D., of the Dana-Farber Cancer Institute, who was not part of the study.

“By and large, you can give those drugs for months and sometimes even years without big increases in cumulative toxicity,” he said.

But before the two-drug combination is accepted, he said, he and others are likely to wait to see what effect — if any — it has on overall survival.

“If longer progression-free survival tracks with overall survival, the interest is higher,” he said.

The study was supported by Genentech, which markets Avastin and Tarceva. Dr. Miller and colleagues reported financial links with the company. Dr. Johnson reported financial links with Genzyme, Boston Scientific, Celgene, and Johnson and Johnson.

Primary source: Journal of Clinical Oncology

Source reference:

Miller VA, et al “A randomized, double blind, placebo controlled, Phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for 1st-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC)” J Clin Oncol 2009; 27(15S): Abstract LBA8002.

Boehringer Ingelheim will present new data on the company’s two lead oncology compounds, BIBW 2992* and BIBF 1120** at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO), the company announced today. Two studies in the LUX-Lung clinical development programme for BIBW 2992 and a Phase II study of BIBF 1120 in ovarian cancer patients will be presented.

LUX Lung 2 interim results

Interim Phase II data from the LUX-Lung 2 study suggest BIBW 2992 has anti-tumour activity in advanced second-line non-small cell lung cancer (NSCLC) patients who have epidermal growth factor receptor (EGFR) mutations.1

“Lung cancer kills more people than any other cancer.3 The LUX-Lung 1 and 2 studies represent an opportunity to investigate BIBW 2992 across a range of different patient populations,” said Dr Manfred Haehl, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The preliminary data from the LUX-Lung 2 study suggests that BIBW 2992 may have activity in the second-line setting among NSCLC patients with EGFR mutations, which is encouraging news.” 1 BIBW 2992 is an orally administered irreversible dual inhibitor of the epidermal growth factor receptor (EGFR) and human epithelial receptor 2 (HER2) tyrosine kinases.4 It is the first irreversible EGFR-TKI (tyrosine kinase inhibitor) to reach Phase III for third/fourth-line NSCLC.5

In the emerging era of personalised cancer medicine, Boehringer Ingelheim is one of the first companies to prospectively identify appropriate patients for clinical trials based on biomarkers. As part of the LUX-Lung clinical development programme, Boehringer Ingelheim is evaluating BIBW 2992 in NSCLC patients who test positive for EGFR activating mutations.

“It is well documented that ‘activating’ mutations that arise in the tyrosine kinase (TK) domain of the EGFR gene are associated with an increased sensitivity to first generation EGFR TKIs.6,7,8 The majority of patients who initially respond to EGFR TKIs such as gefitinib or erlotinib will eventually develop resistance, often through gaining another mutation, such as the so-called T790M resistance mutation,”9,10 said Dr Haehl.

Detailed Findings from LUX-Lung 2:1

To date, 409 NSCLC patients have been screened in the LUX-Lung 2 study and 104 patients with EGFR mutations have started treatment with BIBW 2992 once daily. Preliminary data will be presented at ASCO for the first 73 second line patients, all of whom had previously received one regimen of chemotherapy. 67 patients are evaluable for response.

Interim data show:1

- 64% of patients (43/67) taking BIBW 2992 in the 2nd line setting experienced a partial response (75% among patients with deletion 19 and 66% in patients with L858R mutations)
- 31% (21/67) of patients taking BIBW 2992 in the 2nd line setting experienced stable disease
- Median progression-free survival (PFS) in 2nd line setting is 10.2 months
- The most common related adverse events were diarrhea and skin-related disorders in 86% and 89% of patients respectively [16% and 18% being grade 3 respectively]
- 37 patients had dose reduction and 4 patient discontinued treatment due to adverse events.

Findings from LUX Lung1

In addition, preliminary data on the demographic and blinded safety data from the ongoing Phase III study, the LUX-Lung 1 trial, will be presented at ASCO for the first time.11

The LUX-Lung 1 study addresses a critical need for treatment options for NSCLC patients after failure with a second-line or third-line reversible EGFR inhibitor (i.e. erlotinib or gefitinib). This study recently moved from Phase IIb into Phase III.2

“The LUX-Lung 1 study is important as it investigates BIBW 2992 in a group of patients for whom there are no other approved treatment options. These are patients who have already been through standard first-line or second-line chemotherapy and then received treatment with an EGFR TKI. The LUX-Lung 1 study will evaluate whether BIBW 2992 will extend the lives of these cancer patients.”11 said Dr. Haehl.

First presentation of Phase II data for BIBF 1120 in ovarian cancer

Data from a Phase II study of BIBF 1120 in patients with ovarian cancer who responded to at least second-line chemotherapy will be presented at ASCO in Orlando. The study showed a potential delay in disease progression: with BIBF 1120 the median time to RECIST progression was 4.8, and 2.8 for placebo.2 BIBF 1120 is an oral compound that works by simultaneously inhibiting vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and fibroblast growth factor receptors (FGFRs) - all factors which are crucially involved in the formation of blood vessels, a process known as angiogenesis.12,13

“There is a great need for more effective and well tolerated treatment options for women with ovarian cancer. We have a growing body of evidence that anti-angiogenic agents may represent an important treatment approach for this disease,” commented Prof. Jonathan A Ledermann, MD, Professor of Medical Oncology & Director at the Cancer Research UK & UCL Cancer Trials Centre, University College London. “These data indicate BIBF 1120 may have a potential role in delaying disease progression in patients with ovarian cancer who had previously responded to chemotherapy.”

Because angiogenesis plays a pivotal role in the growth of solid tumours,13 BIBF 1120 is currently being investigated in a number of cancer types including advanced NSCLC. The LUME-Lung Phase III clinical trial programme is investigating BIBF 1120 in combination with standard second-line chemotherapy treatments for patients with advanced NSCLC. Approximately 2,600 patients will be enrolled, making this one of the largest Phase III study programmes in this NSCLC patient population to date.

About Lung Cancer

Lung cancer is the world’s most common cancer and kills more people than any other cancer.3,14 In 2008, approximately 1.52 million new cases of lung cancer were diagnosed worldwide, with 1.31 million people dying from the disease.14 In the United States, an estimated 161,840 deaths, accounting for 29 percent of all cancer deaths, occurred in 2008, according to the American Cancer Society (ACS).15

About Ovarian Cancer

According to the 2008 World Health Organization World Cancer Report, as of 2002, ovarian cancer was ranked as the 6th most common cancer in women. Additionally, approximately 204,000 new cases were diagnosed worldwide and 125,000 women died from the disease in 2002.14 The ACS estimates that about 21,650 new cases of ovarian cancer were diagnosed in the United States (U.S.) during 2008. Only forty-five percent of women with ovarian cancer are still alive at least five years after diagnosis in the U.S.16

About Boehringer Ingelheim in Oncology

Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research programme to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world’s leading cancer centres, Boehringer Ingelheim is committed to discovering and developing novel cancer treatments. This commitment is underpinned by using advances in science to develop a range of targeted therapies in areas of medical need, including various solid tumours and haematological cancers.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. BIBW 2992 entered Phase IIb/III clinical development in NSCLC earlier in 2008 and was granted Fast Track designation for a third/fourth line treatment indication in NSCLC by the US Food & Drug Administration. In addition, the LUME-Lung Phase III clinical trial programme, which is investigating BIBF 1120 in combination with standard second-line chemotherapy treatments for patients with advanced NSCLC, is currently ongoing. In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing inhibitors of polo-like kinase 1 (Plk1), a protein that is involved in the processes of cell division. These molecules are in the early stages of clinical development.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of $11.6 billion euro (17 billion) while spending one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For U.S. journalists, please visit http://us.boehringer-ingelheim.com

Note

Please be advised this release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document.

* (planned trade name Tovok™)
** (planned trade name Vargatef™)

References:

1. Shih J-Y et al. “A Phase II study of BIBW 2992, a novel irreversible dual EGFR and HER2 tyrosine kinase inhibitor (TKI), in patients with adenocarcinoma of the lung and activating EGFR mutations after failure of 1 line of chemotherapy (LUX-Lung 2).” Poster Discussion Presentation. 1 June 2009, Session Time: 8:00AM - 12:00PM. #8013

2. Ledermann, J. A. “A randomised Phase II placebo-controlled trial using maintenance therapy to evaluate the vascular targeting agent BIBF 1120 followign treatment of relapsed ovarian cancer (OC).” Oral presentation, Clinical Science Symposium. Monday, 1 June 2009, Session Time 9:45AM - 11:15AM. # 5501

3. “Ask the Expert Online Q&A: Are the number of cancer cases increasing or decreasing in the world?” 1 April 2008. World Health Organization. 5 May 2009. http://www.who.int/features/qa/15/en/print.html.

4. Li D et al. “BIBW2992, an irreversible EGFR/HER2 inhibitor highlyeffective in preclinical lung cancer models.” Oncogene 2008;27:4702-4711

5. Boehringer Ingelheim Pharmaceuticals. “BIBW 2992 and BSC Versus Placebo and BSC in Non-Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)” 23 April 2009. ClinicalTrials.gov. 5 May 2009.
http://clinicaltrials.gov/ct2/show/NCT00656136?term=BIBW+2992+and+Phase+III&rank=1

6. Lynch, T. J. et al. “Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.” N. Engl. J. Med. 350, 2129-2139 (2004). Available at: http://content.nejm.org/cgi/reprint/350/21/2129.pdf. Accessed on 5 May 2009.

7. Paez, J. G. et al. “EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.” Science 304, 1497-1500 (2004). Available here. Accessed on 5 May 2009.

8. Pao, W. et al. “EGF receptor gene mutations are common in lung cancers from `never smokers` and are associated with sensitivity of tumors to gefitinib and erlotinib.” Proc. Natl Acad. Sci. USA 101, 13306-13311 (2004). Available here. Accessed on 5 May 2009.

9. Riely G. J. et al. “Clinical Course of Patients with Non -Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib.” Clin. Cancer Res, 12, 839-844(2006). Available at: http://clincancerres.aacrjournals.org/cgi/reprint/12/3/839. Accessed on 5 May 2009.

10. Balak, M. N. et al. “Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors.” Clin. Cancer Res. 12, 6494-6500 (2006). Available at: http://clincancerres.aacrjournals.org/cgi/reprint/12/21/6494Accessed on 5 May 2009.

11. Yang C-H et al. “Phase IIb/III double-blind randomized trial of BIBW 2992, an irreversible, dual inhibitor of EGFR and HER2 plus best supportive care (BSC) versus placebo plus BSC in patients with NSCLC failing 1-2 lines of chemotherapy (CT) and erlotinib or gefitinib (LUX-Lung1): a preliminary report. General Poster Session: Lung Cancer - Metastatic.” Saturday 30 May 2009, Session Time: 2:00PM - 6:00PM. # 8062

12. Hilberg F. et al. “BIBF1120 a novel, small molecule triple angiokinase inhibitor: profiling as a clinical candidate for cancer therapy.” European Journal of Cancer Supplements. 2004; 2:50.

13. Lewis J. Kleinsmith. “Understanding Cancer and Related Topics: Understanding Angiogenesis.” Rockville: National Cancer Institute, 2006. Available here. Accessed on 5 May 2009.

14. P Boyle and B Levin (eds). “World Cancer Report 2008.”, World Health Organization: International Agency for Research on Cancer. Lyon: 2008.

15. American Cancer Society. “Cancer Facts and Figures 2008.” Atlanta: 2008. Available at: http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf. Accessed on 5 May 2009.

16. American Cancer Society. “Ovarian Cancer Detailed Guide.” Atlanta: 2008. Available at: http://documents.cancer.org/114.00/114.00.pdf. Accessed on 5 May 2009.

Source
Boehringer Ingelheim

ORLANDO, June 2 — An investigational agent that targets two growth factors — vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) — increased progression-free survival in patients with advanced non-small cell lung cancer, researchers reported here.

Moreover, the “patients felt better when they were on therapy,” said Roy Herbst, M.D., Ph.D., of M.D. Anderson Cancer Center in Houston.

Dr. Herbst reported the results of the Phase III ZODIAC trial of vandetanib (Zactima) given in combination with docetaxel (Taxotere) at the American Society of Clinical Oncology.

Patients randomized to the drug had a median of 17.3 weeks of progression-free survival compared with a median of 14 weeks for the patients who received docetaxel plus placebo, for a hazard ratio of 0.70 (95% CI 0.70 to 0.90), which was significant, (P<0.001), Dr. Herbst said.

• Explain to interested patients that the drug described in this trial, vandetanib, is not FDA approved and is not available outside a clinical trial setting.
• Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Dr. Herbst said that during vandetanib treatment patients reported less shortness of breath, chest pain, and coughing compared with controls.

The ZODIAC (Zactima in cOmbination with Docetaxel In non-smAll cell lung Cancer) study enrolled 1,391 patients with stage IIIB/IV NSCLC at 198 centers between May 2006 and April 2008. All had previously failed first-line standard chemotherapy.

The median follow-up was 12.8 months.

The secondary endpoint — overall survival — did not reach significance, with median overall survival 10.6 months in the vandetanib arm versus 10.0 in the control arm. But, in an interview Dr. Herbst said he thought there would be a statistically significant overall survival benefit as the data matured.

More toxicities were reported in the vandetanib arm — diarrhea, rash, and neutropenia — but there was not more bleeding, which Dr. Herbst said was encouraging since bleeding, including pulmonary bleeding, is a significant side effect with drugs that target VEGF. “And there was less nausea and vomiting in the vandetanib arm,” he said.

About 22% of patients in the study discontinued vandetanib because of side effects.

In an interview with MedPage Today, Dr. Herbst addressed the issue of cost for targeted therapies such as vandetanib for treatment of lung cancer. While acknowledging that the cost for treatment was likely to be high, he said that “by attacking the cancer at both ends — the blood supply [with VEGFR] and the tumor cells [with EGFR], the net result might be a cost savings, because I think it would be cheaper because it has the potential of avoiding the need for other therapies.”

The trial was supported by AstraZeneca, which is developing vandetanib. Dr. Herbst disclosed that he has a consultant or advisory role with AstraZeneca Oncology and said he received research funding from AstraZeneca Oncology.

Primary source: American Society of Clinical Oncology

Source reference:
Herbst RS, et al “Vandetanib plus docetaxel versus docetaxel as 2nd-line treatment for patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZODIAC)” ASCO 2009; Abstract CRA800.

Cancer patients who are older than 65 years have poorer physical health and, in some cases, mental health when compared with people of the same age group without cancer, according to a study in the June 9 online issue of the Journal of the National Cancer Institute.

Because health-related quality of life (HRQOL) before cancer is not often measured, the impact of cancer on HRQOL is poorly understood.

To quantify the changes before and up to 2 years after cancer diagnosis, Bryce B. Reeve, of the Division of Cancer Control and Population Sciences at the National Cancer Institute in Bethesda, Md., and colleagues looked at changes in HRQOL from 1998 through 2003 in 1,432 patients aged 65 years or older. They compared the patients who were enrolled in Medicare managed care plans with 7,160 matched control subjects, by using data from the Surveillance, Epidemiology, and End Results registry linked with Medicare Health Outcomes Survey (MHOS).

For patients diagnosed with prostate, breast, bladder, colorectal, kidney, or non-small cell lung cancers, or non-Hodgkin lymphoma, the researchers observed a statistically significantly greater decline in physical health of patients compared with control subjects without cancer. They also found that patients with prostate, colorectal, or non-small cell lung cancer experienced statistically significantly decreased mental health relative to matched control subjects without cancer.

“We expect this study to provide a benchmark for capturing the burden of cancer on HRQOL and an evidence base for future research and clinical interventions aimed at understanding and remediating these effects,” the authors write.

In another study, also published in this issue, John L. Gore, of the Robert Wood Johnson Clinical Scholars Program at the University of California, Los Angeles, and colleagues describe HRQOL outcomes among patients 48 months after treatment for localized prostate cancer. This team, which used questionnaires that measure generic physical and mental health, as well as dysfunction specific to prostate cancer treatment, found that urinary incontinence was more common after prostatectomy than after brachytherapy or external beam radiation therapy and that sexual dysfunction “profoundly” affected all treatment groups.

“These results may guide decision making for treatment selection and clinical management of patients with health-related quality-of-life impairments after treatment for localized prostate cancer,” the authors write.

In an accompanying editorial, Pamela J. Goodwin, M.D., and Srikala S. Sridhar, M.D., of the Princess Margaret Hospital and the Samuel Lunenfield Research Institute at Mount Sinai Hospital in Toronto reiterate the importance of the studies, but point out several limitations to both.

They point out that Reeve et al. left out younger age groups, had a short study period, and produced findings not sufficiently linked to specific cancer treatments to assist patients with making decisions about treatment. Gore et al., according to the editorialists, did not address multimodality treatment and the impact of this combined approach–a growing trend for patients with aggressive disease.

“These two reports have added to our knowledge about quality of life in cancer patients,” the editorialists write. “However, further research is needed to better understand the short and longer term impact of cancer diagnosis and treatment on overall quality of life, especially as screening becomes more common, our anticancer treatments improve, and patients live longer after a diagnosis of cancer.”

Citations:

Article 1:
“Impact of Cancer on Health-Related Quality of Life of Older Americans.”
Reeve et al.
J Natl Cancer Inst 2009, 101: 860-868.

Article 2:
“Survivorship Beyond Convalescence: 48-Month Quality-of-Life Outcomes After Treatment for Localized Prostate Cancer.”
Gore et al.
J Natl Cancer Inst 2009, 101: 888-892.

Editorial:
“Health-Related Quality of Life in Cancer Patients - More Answers but Many Questions Remain.”
Goodwin P and Srikala Sridhar.
J Natl Cancer Inst 2009, 101: 838-839.

Source
Journal of the National Cancer Institute