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Emerging Methods to Treat Non–Small-Cell Lung Cancer


Tim Casey

Atlanta—Recent advances in treating patients with non–small-cell lung cancer (NSCLC) may lead to better results and cost-savings, according to a physician and pharmacist who spoke at the AMCP meeting. Doctors are embracing molecular profiling to develop individualized therapies, and they will likely increase use of biomarkers and companion diagnostics in the coming years. The topic was discussed during a satellite symposium at the AMCP meeting titled Non–Small-Cell Lung Cancer: Correlating Guidelines and Evidence to Formulary Development. Molecular Profiling of Tumors Vincent A. Miller, MD, attending physician at Memorial Sloan-Kettering Cancer Center in New York, New York, began with an overview of NSCLC. He noted that approximately 85% of lung cancers are classified as NSCLC, which is divided into 3 subtypes based on the size, shape, and chemical composition of the cells. Squamous cell carcinoma, which has been linked to smoking and is normally found in the middle of the lungs, accounts for approximately 25% to 30% of all lung cancers. Adenocarcinoma, which is usually found in the periphery of the lung, accounts for approximately 40% of lung cancers. Large-cell carcinoma, which is found in any part of the lung and spreads quickly, accounts for approximately 10% to 15% of lung cancers. Because of the differences in the cancers and the evolving nature of the disease, doctors are learning new information about the disease and must be cognizant of the latest developments, according to Dr. Miller. “This is a challenging area for us,” Dr. Miller said. “It’s hard to keep up with everything.” Lung cancer is the leading cause of cancer-related deaths in both men and women. In 2011, an estimated 156,940 people will die of lung cancer and 221,130 new cases of lung cancer will be diagnosed, according to data from the American Cancer Society that Dr. Miller cited. In recent years, the number of men with lung cancer has decreased because of a drop in smoking, but the number of women with lung cancer has remained consistent, according to Dr. Miller. When people are suspected of having lung cancer, they are normally evaluated with a chest x-ray, a computed tomography scan, and/or a positron emission tomography scan. If they have a peripheral tumor, optional procedures include percutaneous fine needle aspirate, bronchoscopy, video-assisted thoracoscopy, and thoracoscopy without video assistance. If they have a central tumor, optional procedures include sputum cytology, bronchoscopy, percutaneous fine needle aspirate, and thoracotomy. Dr. Miller mentioned the most effective treatment for advanced NSCLC is a 2-drug, platinum-based chemotherapy regimen, which can improve overall survival and quality of life. He said that chemotherapy is better than best supportive care, a 2-drug chemotherapy regimen is preferred over 1-drug or 3-drug chemotherapy regimens, and third-generation drugs are superior to older regimens. Dr. Miller then provided results from two phase 3 trials involving drugs commonly used to treat NSCLC (bevacizumab and pemetrexed). In the first, 850 patients with nonsquamous NSCLC were randomized to receive paclitaxel and carboplatin (PC) or paclitaxel, carboplatin, and bevacizumab (PCB). After 3 years of treatment, the median progression-free survival was 6.2 months in the PCB group compared with 4.5 months in the PCgroup (P<.001; hazard ratio [HR], 0.66). The median overall survival after 3 years was 12.3 months in the PCB group compared with 10.3 months in the PCgroup (P=.003; HR, 0.79). The other study evaluated patients with advanced NSCLC who were randomized to receive cisplatin and pemetrexed or cisplatin and gemcitabine. The pemetrexed group had a median progression-free survival of 4.04 months compared with 1.97 months for the other group (P<.00001; HR, 0.599). Median overall survival was 13.4 months in the pemetrexed group and 10.6 months in the other group (P=.012; HR, 0.79). Molecular profiling is becoming more popular in helping treat NSCLC, according to Dr. Miller. He said 85% to 90% of mutations in the epidermal growth factor receptor (EGFR) gene found in patients with NSCLC are in-frame deletions in exon 21 and point mutations in exon 21. In a trial of patients who mostly lived in Asia, patients who were mutation positive and received gefitinib or carboplatin plus paclitaxel had a longer progression-free survival and better overall response rate than if the mutation was negative. In addition, gefitinib proved to be significantly more effective than PC. Based on the results of that study and other trials, Dr. Miller said there has been a paradigm shift in treating NSCLC. He said physicians first perform a biopsy on the tumor. If activating mutations are present, they give patients an EGFR tyrosine kinase inhibitor. If there are no mutations, they examine histology and clinical features. According to Dr. Miller, from 1975 to 2010 treatment with an EGFR tyrosine kinase inhibitor led to a response rate of 75%, 1-year overall survival of approximately 80%, and 2-year overall survival of approximately 55%. Meanwhile, treatment with 2 drugs led to a response rate of 25%, 1-year overall survival of 35%, and 2-year overall survival of approximately 20%; treatment with 2 drugs plus bevacizumab led to a response rate of 35%, 1-year overall survival of 50%, and 2-year overall survival of approximately 20%. “This is where we’re going,” said Dr. Miller, referring to a greater emphasis on EGFR tyrosine kinase inhibitors. Formulary Discussions to Individualize Care H. Eric Cannon, PharmD, chief of pharmacy at SelectHealth in Murray, Utah, followed by discussing the history and costs associated with lung cancer. Lung cancer affects 1.37 million people per year. Based on data published in 2006, 1-year survival rates improved from 37% in 1975 to 42% in 2002, whereas the 5-year survival rate remained constant at 16%. Dr. Cannon said patients with NSCLC are expensive to treat and have higher costs due to hospitalization, emergency department visits, outpatient office visits, radiology procedures, laboratory procedures, and prescription drugs. The cost of treating a patient with NSCLC from diagnosis until death or 2 years is $45,897 compared with $2907 for patients who do not have cancer. When patients have to pay for more of their health insurance, they are more likely to stop taking their medications. He cited a study of 13,172,480 people with insurance that found out-of-pocket costs >$200 per month increased the abandonment of prescriptions. He also stressed the importance of initial treatment. In one study, patients who required additional treatment cost $24,858 per month to treat compared with $5709 for patients who required only initial treatment. In July, the US Food and Drug Administration defined an in vitro companion diagnostic device as one that supplies essential information and allows a safe and effective therapy by identifying a person likely to benefit from the treatment, determine people who may be at risk for serious reactions to the therapy, and monitor how a person responds to the therapy. Although companion diagnostics may be effective, Dr. Cannon said that their use could be limited because regulatory approval is difficult, the devices are costly, there is lack of evidence supporting their effectiveness, and patients’ health insurance does not always cover the costs. Researchers are also examining the use of pathways to decrease variability, reduce medication costs, reduce or eliminate medication errors, improve clinical outcomes, and increase patient satisfaction. According to Dr. Cannon, oral therapies can cost between $100,000 and $150,000. A study he discussed found that an on-pathway group had 37% lower costs for chemotherapy and other infused medications, and 39% lower costs for nonchemotherapy medications. The 12-month survival probability was similar in the on-pathway and off-pathway groups (0.45 vs 0.46; P=.867). Although companion diagnostics, biomarkers, and pathways are not often used, Dr. Cannon said they will be more prevalent in the coming years as payers understand their cost-effectiveness and ability to help patients. “They represent a significant advantage,” Dr. Cannon said. “They’ll definitely play a role in the future.”

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