Diagnostic Test to Select Patient Candidates for Novel Investigational Non-Small Cell Lung Cancer Therapy

Abbott's molecular diagnostics business, headquartered in Des Plaines, Ill.,has entered into an agreement with Pfizer Oncoloy, a business unit of Pfizer Inc, committed to the discovery, investigation and development of innovative treatment options for cancer patients worldwide, to develop a molecular diagnostic test intended to screen non-small cell lung cancer (NSCLC) tumors for the presence of gene rearrangements.

Pfizer has developed a novel investigational agent that selectively targets cancer-causing genes implicated in the progress of many cancers. To be eligible to receive Pfizer's oral therapy, a particular genetic translocation (rearrangement) known to be found in NSCLC tumors and a wide variety of other cancers, but not in normal cells, must be present.

Under terms of the agreement, Abbott will develop a companion diagnostic test that will determine a patient's genetic status and will be used in patient selection for future clinical trials of PF-02341066.

"We are very pleased to partner with Abbott to develop a companion diagnostic test for non-small cell lung cancer and ensure its global availability for patients and physicians who need this information to make the best treatment decisions," said Garry Nicholson, General Manager, Pfizer Oncology Business Unit.

"This test will allow us to focus on the patient population most likely to benefit from our NSCLC candidate. Working in close partnership with the experienced Abbott team, we are confident that we will deliver yet another application of personalized medicine to address a currently unmet medical need in NSCLC."

"Pfizer's novel compound for treating non-small cell lung cancer appears to be ideally suited to individualized therapy," said Stafford O'Kelly, head of Abbott's molecular diagnostics business. "Abbott is a leader in the development and commercialization of companion diagnostics and we're delighted to collaborate with Pfizer, a leader in cancer therapeutics, on the development of a test to identify patients who might benefit from this important compound."

Erlotinib Improves Overall Survival After Initial Chemotherapy in Patients with Advanced Lung Cancer

Results from SATURN, a pivotal Phase III study, met a key secondary endpoint of extending overall survival in patients with advanced non-small cell lung cancer (NSCLC) who received erlotinib (Tarceva®, Genentech/Roche; OSI) immediately after their initial chemotherapy. A statistically significant improvement in overall survival was seen in the pre-planned final analysis of the total patient population in the study. The new data will be presented during the 13th World Conference on Lung Cancer to be held July 31 – August 4, 2009 in San Francisco.

Lung cancer is the most common cancer worldwide with 1.5 million new cases annually and NSCLC accounts for 85 – 90% of all lung cancers. Non-small cell lung cancer (NSCLC) progresses rapidly and survival rates are generally very poor. Most people are diagnosed with advanced stage disease and less than 5% of these advanced NSCLC patients survive for five years. Extending the time patients live and managing side effects are key treatment goals.

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.
Treating patients immediately following first-line chemotherapy versus waiting for the cancer to grow or spread before giving additional treatment represents a new approach in advanced NSCLC.

A new approach
Erlotinib is, as a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor, different from conventional chemotherapies.
Over-expression of EGFR is common in several solid tumors, such as colorectal cancer, lung carcinomas, and cancers of the head and neck. It correlates with increased metastasis, decreased survival and a poor prognosis. EGFR protects malignant tumors cells from the cytotoxic effects of chemotherapy and radiotherapy, making these treatments less effective.

HER1 and EGFR receptors are directly involved in inter-cellular signaling in systems governing cell division and proliferation. By interfering with the function of these receptors, which are highly active and often over-expressed in rapidly dividing tumor cells, erlotinib inhibits EGFR-receptor tyrosine kinase activity, and may help to initiate pathways of apoptotic cell death. The interference with the cell signaling pathways involved in cell proliferation represents a novel approach to the treatment of solid tumors.

Today, erlotinib is the first and only EGFR oral targeted agent in second line with a proven and significant survival and symptom benefit in a broad range of patients with advanced lung cancer without the side effects associated with chemotherapy. The drug has been approved in the EU since September 2005 and in the US since November 2004 for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Patient benefit
In the landmark registration study BR.21, a randomised controlled phase III clinical trial comparing erlotinib with placebo/best supportive care in patients with locally advanced or metastatic non-small lung cancer which took place in 17 countries around the world, erlotinib delivered effectiveness comparable to chemotherapy and significantly improves overall quality of life.

The registration study underlined that more patients on erlotinib had improvement in cough, pain, shortness of breath and overall physical function versus patients on placebo. In addition erlotinib did not induce the distressing side-effects associated with chemotherapy, such as nausea and vomiting. An added benefit, improving adherence, is that erlotinib is convenient as patients can take a tablet once a day at home rather than receive intravenous treatments in a hospital.

Global trial
SATURN, a global multicentre, double blind, randomized, prospective phase III study was designed to evaluate the efficacy of erlotinib vs. placebo in patients with advanced, recurrent or metastatic NSCLC who had not progressed following first line platinum-based chemotherapy. The study involved more than 880 patients from approximately 160 centers; 438 received erlotinib and 451 placebo.

The study met its primary endpoint demonstrating a statistically significant extension of the time patients live without their disease worsening; there was a 41% increase compared with placebo (hazard ratio= 0.71, p-value <0.0001).>

“This study has now not only confirmed that immediate treatment with Tarceva after initial chemotherapy delayed the progression of disease, but also importantly helped patients in the study live longer,” said Professor Federico Cappuzzo, M.D., Istituto Clinico Humanitas IRCCS, Milan and principal investigator of the SATURN study. “This is good news for doctors and their patients since advanced lung cancer is one of the most challenging cancers to treat and is often associated with a very short life-expectancy.”

Commenting on the study, William M. Burns, CEO Division Roche Pharmaceuticals said, “This is the second set of data from large studies that has shown Tarceva helps patients with advanced lung cancer to live longer. These results confirm that Tarceva has an important role to play in improving the lives of patients earlier in the management of this devastating disease.”

Erlotinib is already a well established treatment in second-line management of advanced NSCLC after the failure of chemotherapy and is proven to extend survival for a broad range of patients in this setting. Most recently, presentation of the SATURN primary endpoint data analysis at ASCO 2009 showed that patients who received treatment with erlotinib immediately after initial chemotherapy if their cancer had not progressed had a 41% improvement in the length of time they lived without their disease getting worse compared to placebo.

Outcome confirmed
During the Annual Society of Clinical Oncology (ASCO) Vincent A. Miller, MD., a medical oncologist from the Memorial Sloan-Kettering Cancer Center, presented results from the phase III ATLAS study supported findings in the SATURN study.

The ATLAS study, a global multicentre, randomised, double blind, placebo controlled study that enrolled 1,160 patients with locally advanced, recurrent or metastatic NSCLC, was designed to evaluate bevacizumab (Avastin®, Genentech/Roche) in combination with erlotinib (150 mg daily) versus bevacizumab alone, following bevacizumab in combination with a platin-containing doublet chemotherapy, in patients with stage IIIb/IV NSCLC.

The study showed that combined treatment with bevacizumab and erlotinib, immediately following initial therapy with bevacizumab plus chemotherapy was highly effective and significantly delayed disease progression for patients with advanced NSCLC, without the need for chemotherapy.

The positive results from these trials were encouraging because previous Phase III studies in which erlotinib was used as first-line therapy in combination with cytotoxic drugs (the TRIBUTE and TALENT studies) failed to demonstrate a survival advantage when erlotinib was added to conventional treatment regimens.

The overall survival data fron SATURN will be used to support the European and US applications for use of erlotinib as a first-line maintenance treatment for patients with advanced NSCLC. These applications were made to the European Medicines Agency (EMEA) and US Food and Drug Administration (FDA) in March 2009 and are based on the pivotal Phase III SATURN trial. The FDA Prescription Drug User Fee Act (PDUFA) review date will be on or about January 18, 2010.

Commenting on the overal product development, Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals, Roche's US partner, said:"We are pleased with the launch of Tarceva in the U.S. to date and we continue to believe that Tarceva will emerge as a fundamentally important new agent in changing the paradigm for the treatment of cancer patients around the world. With our partners, Genentech and Roche, we are committed to executing a post-approval development plan, studying Tarceva in earlier stage lung cancer patients, in patients with other tumor types and combinations with other targeted therapies."

For more information:

• Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, et al. Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial. Journal of Clinical Oncology, Vol 25, No 12 (April 20), 2007: pp. 1545-1552.
• Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, et al. TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 5892-5899.
• National Cancer Institute: Erlotinib (Tarceva®) Extends Survival in Advanced Lung Cancer
• Tarceva (erlotinib) USA website for healthcare professionals
• Tarceva (erlotinib) Global website for healthcare professionals
• Garcia M et al. Global Cancer Facts & Figures. Atlanta, GA: American Cancer Society, 2007.
• Highlights of Prescribing Information (USA)

ASCO 2009 Annual meeting:

• Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, et al. SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC. J Clin Oncol 27:15s, 2009 (suppl; abstr 8001). Abstract presented at ASCO 2009 Annual Meeting, Orlando.
• Miller VA, O'Connor P, Soh C, Kabbinavar F. 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 first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 27:18s, 2009 (suppl; abstr LBA8002). Abstract presented at ASCO 2009 Annual Meeting, Orlando.

Also read these PubMed abstracts:

• Allen J, Jahanzeb M. Neoadjuvant chemotherapy in stage III NSCLC. J Natl Compr Canc Netw. 2008 Mar;6(3):285-93.
• Brown ER, Shepherd FA. Erlotinib in the treatment of non-small cell lung cancer. Expert Rev Anticancer Ther. 2005 Oct;5(5):767-75. Review.
• Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, et al. Erlotinib in Previously Treated Non–Small-Cell Lung Cancer. N Engl J Med 2005; 353:123-132. (See also Full Text Article)
• Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, et al. Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome. N Engl J Med. 2005 Jul 14;353(2):133-44 (See also Full Text Article).
• Sandler A. Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib. Oncology (Williston Park). 2003 Nov;17(11 Suppl 12):17-22

Information for your patient:

• Tarceva (erlotinib) USA patient website.
• Tarceva (erlotinib) Global patient website.

Images courtesy American Society of Clinical oncology (ASCO)

Pemetrexed First Agent Approved in Europe as Maintenance Therapy for Advanced, Nonsquamous Non-Small Cell Lung Cancer

The European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) has granted approval for the use of pemetrexed for injection (Alimta ®, Eli Lilly and Company) as monotherapy for maintenance treatment of patients with other than predominantly squamous cell histology in locally-advanced or metastatic non-small cell lung cancer (NSCLC), whose disease has not progressed immediately following platinum-based chemotherapy. This approval is based on data that showed pemetrexed improved overall survival in other than predominantly squamous NSCLC patients in the maintenance setting.

Globally, lung cancer is the most common form of cancer and the biggest killer, causing 1.3 million cancer deaths annually. This is more than breast, colon and prostate cancer taken together. About 85 - 90 percent of all lung cancers are non-small cell lung cancer (NSCLC). Survival rates are very poor.

Major disease forms
Non-small cell lung cancer (NSCLC) is defined as a group of histologies, that is, tumor types differentiated by cellular structure. The most predominant is squamous cell carcinoma (also known as epidermoid carcinoma) which accounts for 30 - 40% of all NSCLC cases. Formed from round cells that replace damaged cells along the epithelium of the main, lobar or segmental bronchi, this disease is a relatively slow growing carcinoma with a relatively good prognosis. Recurrence rates for resected squamous cell carcinoma are relatively low compared top other types of NSCLC, with distant metastases less common given the same treatment at the same stage.

Also referred to as nonsquamous histology, adenocarcinoma, which account for more than half of all NSCLC diagnoses, usually arises from mucus-producing cells of the lung. Aproximately two-thirds of adenocarcinomas develop in the outer regions of the lung, while the remaining one-third develop centrally. The majority of adenocarcinomas are asymptomatic until they have progressed to an advanced stage. As a consequence, the prognosis is generally worse compared to that of squamous cell carcinoma. On the other hand, once diagnosed, adenocarcinomas generally respond better to treatment than other NSCLC histologies.

Squamous cell carcinoma tends to metastasize in the bone, adrenal glands, liver, small intestines and brain. Because this disease is almost always caused by smoking, occurrence has decreased over the past 30 - 35 years.

Other types of NSCLC include bronchoalveolar carcinoma (BAC), a subclassification of adenocarcinoma with distinct clinical and pathologic properties and large cell carcinoma.

The majority of patients with NSCLC eventually develop metastatic disease or disease that is not a candidate for surgical interventions. this makes them potential candidates for systemic therapies. However, the decision on whether a patient receives therapy, greatly depends upon a number of factors, including the disease stage. In general, the more advanced the disease is, the more likely that a physician will prescribe a drug therapy.

Staging of Lung Cancer
Lung Cancer is often classified according to the American Joint Commitee on Cancer (AJCC) TNM staging system, and has five-tier staging, starting at 0 and rising to the severity of stage IV.

The primary T1 tumor, generally smaller than 3 centimeter, is usually easy to define on computed tomography (CT) and fluorodeoxyglucose positron emission tomography (FDG-PET).

TNM stage T3 tumors include tumors of any size with direct extension into the chest wall, diaphragm, mediastinal pleura or pericardium. Stage T4 tumors invade the mediastinum, great vessels, trachea, oesophagus and vertebral bodies.

Lung cancer in metastatic stage becomes aggressive. In this stage a therapy to shrink tumour size, stabilize the disease and relieve debilitating symptoms, with minimal toxic effects of the drug is required. Pemetrexed is the most promising molecule in that aspect. The drug provides better survival, progression free time and response and has superior tolerability than other cytotoxic drugs used for the same condition.

Mechanism of action
Pemetrexed is a multitargeted antifolate currently approved for first-line treatment of advanced, other than predominantly squamous NSCLC in combination with a platinum-based chemotherapy, and as a single agent in the second-line setting for advanced, other than predominantly squamous NSCLC patients with recurrent disease. Pemetrexed is chemically similar to folic acid and is in the class ofchenotheray drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT).

Improve Overall Survival in a Maintenance Setting
The concept of maintenance therapy represents a paradigm shift in the treatment of advanced, other than predominantly squamous NSCLC.

Traditionally, patients who respond to first-line chemotherapy are monitored until the disease recurs and are then treated with a second-line regimen. In maintenance therapy, rather than halting further treatment until disease progression, patients who respond to a first-line therapy are treated immediately with a maintenance regimen.

"The idea behind ALIMTA as maintenance therapy for nonsquamous, non-small cell lung cancer is to treat patients immediately following their initial course of therapy, in an effort to prolong survival," said Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader at Lilly. "The study that led to this approval was the first that showed improved overall survival in the maintenance setting for NSCLC. This was also the third trial to show the benefit of tailoring ALIMTA treatment to the nonsquamous NSCLC patient population."

Overall survival data for pemetrexed as a maintenance therapy for NSCLC was presented on May 31, 2009, at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) by Chandra P Belani M.D.

The trial compared efficacy with respect to overall survival of pemetrexed plus best supportive care versus placebo plus best supportive care in 663 patients with stage IIIB/IV NSCLC whose disease had not progressed after four cycles of platinum-based induction chemotherapy. Pemetrexed was not included among the induction regimens studied in the maintenance trial. The trial supported two previous studies looking at the use of histology to tailor treatment for patients with advanced, other than predominantly squamous NSCLC.

Patients in the trial were treated with pemetrexed (500 mg/m2 on day one of each 21-day cycle) plus best supportive care or placebo plus best supportive care. All patients were supplemented with vitamin B12, folic acid and dexamethasone.

Pemetrexed was initially approved by the FDA in 2004 for the treatment of mesothelioma, with subsequent approval for second-line treatment of NSCLC.

This latest approval for pemetrexed - the fourth in Europe - follows an initial positive opinion issued by the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) on May 29, 2009, and the recent approval by the U.S. Food and Drug Administration (FDA) of pemetrexed for maintenance therapy in advanced, nonsquamous NSCLC patients whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.

Apart from the existing approvals in the EU and U.S. for the use of pemetrexed in the treatment of patients with locally-advanced or metastatic other than predominantly squamous NSCLC, pemetrexed is also approved, in combination with cisplatin, in both the EU and U.S. for the treatment of chemotherapy naive patients with unresectable malignant pleural mesothelioma.

For more information:

• Official Lilly Physician Resource for pemetrexemed
• Commitee for Medicinal Products for Human Use Post-Authorisation Summary of Positive Opinion for Alimta (EMEA)
• American Cancer Society: Lung Cancer - Non-Small Cell
• C. P. Belani, T. Brodowicz, et al. Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC). Abstract #CRA8000. 2009 American Society of Clinical Oncology (ASCO) Annual Meeting. J Clin Oncol 27:18s, 2009 (suppl; abstr CRA8000).
• C.P. Belani. Maintenance Pemetrexed Plus Best Supportive Care (BSC) Versus Placebo Plus BSC: A Phase III Study in NSCLC. ASCO 2009 Annual Meeting. Oral presentation (Oral Presentation Chair(s): Jyoti D. Patel, MD; Karen L. Reckamp, MD)
• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (Version 2.2006). Non-Small Cell Lung Cancer.
• Staging of non-small cell lung cancer (NSCLC)
• About the TNM System (Blog)
• American Joint Committee on Cancer: PowerPoint Presentation; Staging Lung Cancer.
• Mayo Clinic: Lung Cancer
• Lung Cancer Alliance

Also read these PubMed abstracts:

• Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C. Pemetrexed in the treatment of advanced non-squamous lung cancer. Lung Cancer. 2009 Jul 3. [Epub ahead of print]
• Bobin-Dubigeon C, Amiand MB, Herrenknecht C, Bard JM. Development and validation of an improved liquid chromatography-mass spectrometry method for the determination of pemetrexed in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Jun 21. [Epub ahead of print].
• Belli C, Fennell D, Giovannini M, Gaudino G, Mutti L. Malignant pleural mesothelioma: current treatments and emerging drugs. E xpert Opin Emerg Drugs. 2009 Jun 24. [Epub ahead of print]
• Racanelli AC, Rothbart SB, Heyer CL, Moran RG. Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res. 2009 Jul 1;69(13):5467-74. Epub 2009 Jun 23.
• Vlastos F, Hillas G, Vidal P, Lacomme S, Galateau-Sallé F, et al. Survey and Biological Insights of Pemetrexed-Related Therapeutic Improvement in Mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort. J Thorac Oncol. 2009 Jun 19. [Epub ahead of print]
• Comella P, Chiuri VE, De Cataldis G, Filippelli G, Maiorino L, et al. Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer A randomized phase II SICOG trial. Lung Cancer. 2009 Jun 20. [Epub ahead of print]
• Scagliotti GV, Ceppi P, Capelletto E, Novello S. Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40. Review.

How to help your patients:

• Encourage your patients to have an open, honest talk with you. Tell them that they should feel free to ask any question that’s on their mind, no matter how small it might seem. Also, encourage your patients to talk to other healthcare professionals, including nurses, social workers, and other members of the healthcare team.

Patient resources:

• ASCO’s Guideline on Adjuvant Treatment for Lung Cancer

Images courtesy American Society of Clinical oncology (ASCO)

New Studies Help Advance Understanding and Treatment of Lung Cancer

Findings from several large studies on lung cancer were released at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held in Orlando, Florida, from May 27 – June 2, 2009.

Today, 1.3 million new cases of lung cancer are diagnosed every year around the worls. The vast majority of lung cancers are caused by cigarette smoking. In the United States 350,000 people are living with lung cancer at any given time. Until the late 1990s, lung cancer was the most frequently occurring cancer in the UK. It has now been overtaken by breast cancer, but still accounts for around 1 in 7 new cancer cases.

In recent years, better diagnostics, reduction in smoking and better treatment options have resulted in a lower number of new cases and reported deaths. But regardless these improvements, lung cancer remains the second most common of diagnosed cancers and the number one of cancer-related deaths in the U.S.

“Lung cancer is one of the most challenging cancers to treat, but the studies presented during the annual ASCO-meeting highlight promising new targeted therapies and milder treatment regimens that improve survival,” said Bruce E. Johnson, MD, Director of the Dana-Farber Harvard Medical Center Lung Cancer Program.

Researchers also report that hormone therapy among menopausal women with lung cancer is associated with a higher risk of death. These findings add to growing concerns about the safety of hormone therapy. The studies being highlighted in OncoZine – The International Cancer Blog include:

• Pemetrexed extends survival as maintenance therapy: A phase III study reports that maintenance therapy with pemetrexed (Alimta, Eli Lilly and Company) improves overall survival in nonsquamous forms of advanced non-small cell lung cancer (NSCLC).
• Maintenance therapy with two targeted therapies is superior to one alone: A phase III trial finds that adding erlotinib (Tarceva, Genentech/Roche) to bevacizumab-based (Avastin, Genentech/Roche) maintenance therapy in patients with advanced NSCLC delays cancer progression more than maintenance treatment with bevacizumab alone.
• Menopausal hormone therapy with estrogen and progestin linked to increased risk of death in women with lung cancer: A secondary analysis from the Women’s Health Initiative reports that use of hormone therapy with estrogen plus progestin increases the risk of dying from NSCLC for women with the disease.
• Novel therapy that targets two receptors benefits patients with advanced lung cancer: A phase III trial demonstrates that vandetanib (Zactima, AstraZeneca), a novel drug that targets two key receptors associated with lung cancer growth, improves progression-free survival in patients with advanced NSCLC.

For more information:

• American Society of Clinical Oncology
• 2009 ASCO annual meeting abstracts

Reference:

• The International Medical-Oncology Library (at Boomja.com)

Drug information:

• Pemetrexed (Alimta, Eli Lilly and Company)
• Erlotinib (Tarceva, Genentech/Roche)
• Bevacizumab (Avastin, Genentech/Roche)
• Vandetanib (Zactima, AstraZeneca)

General information:

• Lung Cancer Alliance.
• The Wellness Community.
• American Cancer Society. How Is Non-Small Cell Lung Cancer Diagnosed? Common Signs and Symptoms of Lung Cancer.
• Cancer Research UK – Lung Cancer at a Glance

Illustration courtesy of the American Society of Clinical Oncology.

European specialists are joining forces to improve lung cancer treatment

Prevention, personalized therapies and closer collaborations between surgeons, medical oncologists and radiation oncologists will result in better outcomes for lung cancer patients and those at risk, a leading European expert says.

“Lung cancer is a complex disease. It is one of the most complex cancers, and the more we learn about the biology of the disease, the more we realize that improved cancer care will result from multidisciplinary treatment,” said Prof Robert Pirker, from the Medical University of Vienna, Austria (Spitalgasse 231090 Wien 9., Alsergrund, Wien, Austria). Prof Pirker is co-chair of the scientific committee of a new medical conference, the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), being held for the first time this year, 1-3 May, at the Palazzo dei Congressi in Lugano, Switzerland.

The conference aims to further clinical and scientific cooperation between disciplines to help in the fight against lung cancer. Designed as a regular multidisciplinary, educational meeting, the organizers feel that the meeting may help strengthening general knowledge and providing an updated overview of prevention, screening, diagnosis, treatment modalities and results of translational research. One of the goals of the organizers is to facilitate interaction between the specialties in order to promote an integrated approach to diagnosis and treatment of chest tumors and to strengthen European cooperation and scientific exchange in multidisciplinary management of lung cancer.

A common cancer
Lung cancer is the most common cancer in the world. In men, the highest incidence rates are seen in Europe (especially eastern Europe) and North America. In women, high incidence rates are found in North America and in Europe, particularly in northern and western Europe.

Role of tobacco and smoking
Tobacco smoking is well established as the main cause of lung cancer and about 90% of cases are thought to be tobacco related. There is a clear dose-response relation between lung-cancer risk and the number of cigarettes smoked per day, degree of inhalation, and age at initiation of smoking. Researchers have noted that someone who has smoked all his life has a 20 -30 times greater risk of getting lung-cancer than a non-smoker. The link between tobacco-use and smoking is further emphasized by the fact that the risk of lung cancer decreases with time since smoking cessation.

Research has also shown that while the incidence of lung cancer among men in many Western European countries has been decreasing since the 1980s, the age-adjusted rate for men in other European countries increased at least until the 1990s. Among women this peak in incidence had not been reached in the 1990s. At the same time, the proportion of adenocarcinoma in both men and women has been increasing over time. The most likely explanation for this trend is the shift to low-tar filter cigarettes.

Screening Emphasized
Since the early 2000’s there has been renewed interest in screening because spiral computerized tomography (CT) can detect small asymptomatic lesions more effectively than conventional radiography. Although cure rates for such lesions are very good, there is to date no evidence for effectiveness of mass-screening strategies.

Targeted therapies
Over the past 5 years, researchers have established that for patients with operable cancer, surgery followed by chemotherapy can result in good outcomes. Now, large clinical trials are beginning to evaluate that adding molecular targeted therapies can further improve the chance of a successful outcome for some patients. In addition, doctors are now attempting to refine their treatments based on the clinical characteristics of individual patients, and based on the molecular profile of their tumor.

“More sophisticated and complex treatments require more cooperation,” Prof Pirker says. “That is one of the reasons why we have organized this conference. We believe the result will be better outcomes for lung cancer patients.”

For patients with metastatic disease, targeted therapies have already entered clinical practice or have shown survival benefit in clinical trials. Combinations of chemotherapy and radiotherapy are also improving outcomes of loco-regional non-small-cell lung cancer. “Cure is now possible in about 15% to 20% of patients whose disease can be treated in this way,” adds Prof Jean-Paul Sculier, from Institut Jules Bordet in Brussels, Belgium. (121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel 121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel, telephone +32 254 1311). Prof Sculier will chair a session on treating advanced disease at the conference.

During the European Multidisciplinary Conference in Thoracic Oncology Research groups will present new data that reflect these developments, including:

• A study comparing radiotherapy alone to sequential chemotherapy and radiation in locally advanced non-small-cell lung cancer, plus a correlation of gene expression level with survival (UK).
• Promising results from a study of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small-cell lung cancer (Poland).
• Confirmation that EGFR mutations (deletion in exon 19, missense L858R) are the most important predictors of sensitivity to tyrosine-kinase inhibitor targeted therapies (Italy)
  

Barbara Zolty from the World Health Organization (Avenue Appia 20 1211 Geneva 27 Switzerland telephone +4122791211) will also highlight the importance of preventing lung cancer as the first and foremost weapon against lung cancer. Ms Zolty will speak about the WHO Tobacco-Free Initiative with an enlightening keynote lecture entitled “A thousand seconds, a thousand lives.”

The EMCTO Conference is co-organized by the European Society for Medical Oncology (ESMO), the European Society for Therapeutic Radiology and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS)

For more information also read:

• Janssen-Heijnen ML and Coebergh JW, The changing epidemiology of lung cancer in Europe, Lung Cancer. 2003 Sep;41(3):245-58 )