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Improving the Odds in Lung Cancerby Dianne Witter
It’s been decades since the last substantial advances were made in the treatment of lung cancer; progress against this tenacious and lethal disease has been incremental at best. That is, until now. In the last few years, several advances have significantly improved treatment success rates. As a result, more people than ever before can expect to survive lung cancer today. For instance, last June, a study in the New England Journal of Medicine documented a substantial benefit from adding chemotherapy to the treatment regimen after surgery in certain lung cancer patients. The study reported a 15% improvement in the 5-year survival rate in people who were given chemotherapy after surgery for early-stage non-small cell lung cancer (NSCLC). (About 80% of lung cancers are the non-small cell type.) “These results were amazing,” said Katherine Pisters, M.D., a professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas M. D. Anderson Cancer Center and author of an editorial accompanying publication of the study. In the study, cisplatin and vinorelbine were administered to patients with early-stage disease and good performance status whose tumors had been completely removed surgically. Five years later, 69% of them were still alive compared with 54% who underwent surgical resection only. Previous studies had shown conflicting results, and there was no consensus among physicians about the best treatment. “This trial was the first to treat all patients with a ‘third generation’ chemotherapy agent (vinorelbine) and focus on a narrow subgroup of patients with operable tumors,” said Dr. Pisters. “The findings of this study were supported by two similar randomized trials that also found improved survival. These results have defined a new standard of care for patients with operable lung cancer.” Combined Treatments in Advanced Disease There is also good news in the treatment of more advanced lung cancer. The concept of combining two molecularly targeted therapies or combining one such therapy with chemotherapy in people with more advanced NSCLC has also been shown to extend survival in some studies. Roy Herbst, M.D., Ph.D., a professor in the Department of Thoracic/Head and Neck Medical Oncology, has led a number of studies in this area.
Dr. Herbst is currently looking at the synergistic effects of pairing erlotinib (Tarceva) and bevacizumab (Avastin) in the treatment of patients with advanced NSCLC. “Tarceva is an anti-epidermal growth factor receptor (EGFR) inhibitor; it’s a small molecule that works inside the cell to inhibit tumor cell growth and block synthesis of angiogenic proteins,” he explained. “Avastin is a monoclonal antibody that works on the outside of the cancer cell to inhibit angiogenesis, starving the tumor of the blood supply it needs to grow. Each drug has been shown to improve survival in its own right—Avastin in combination with chemotherapy in the front-line setting and Tarceva in the second-line setting. That’s why giving them as a combined treatment makes so much sense.” After encouraging results in phase I and II studies, Dr. Herbst and colleagues are now doing a multi-institution phase III study. Dr. Herbst adds that, if active, these agents could ultimately be used as adjuvant therapy with even better results. The two drugs are literally combined in the new agent ZD6474, which is also being studied at M. D. Anderson. “It’s a pill that has both the anti-EGFR activity of Tarceva and the anti-cancer activity of Avastin all rolled into one,” Dr. Herbst said. On the basis of initial positive results in clinical studies, a large, randomized trial is planned. In describing his work, Dr. Herbst talks fast and thinks even faster, revealing the urgency he feels about the magnitude of the work to be done. Despite his scientific neutrality, his words carry an undercurrent of enthusiasm, even optimism about the possibilities—not a trait you find in every weary warrior on this battlefield. “Lung cancer is unlikely to respond well to just one agent because it’s a very heterogeneous disease, with many different targets and different mutations,” Dr. Herbst said. “The success with Avastin and Tarceva in combination is promising but, more importantly, it speaks to the need for more studies combining different biologic agents in lung cancer to attack different targets at the same time.” Tyrosine kinase inhibitors that target multiple pathways with one pill are another likely avenue of investigation, he added. “This is just the tip of the iceberg,” he said. “With all the new molecular therapies approved or in the pipeline, as well as more advanced methods of measuring disease status, we can learn how to better pinpoint which patients are most likely to benefit from which combinations of drugs.” In fact, Dr. Herbst notes that a major focus of his group’s current agenda will be to personalize therapy for lung cancer patients on the basis of pretreatment molecular characteristics. The Role of Radiation Therapy
In the past, radiation therapy, used in combination with surgery and/or chemotherapy, has shown definite benefits in lung cancer treatment—but it also had significant drawbacks. The synergistic effects of the combined treatments in some cases caused more serious toxicity, limiting the extent to which radiation could be used. However, recent technological advances have made radiation a more effective contender. “Better immobilization techniques, along with an evolution in the precision of computed tomography and positron emission tomography, have improved our ability to localize the radiation treatment field to the tumor itself and avoid the healthy tissue surrounding it,” said Ritsuko Komaki, M.D., a professor in the Department of Radiation Oncology. As a result, recent studies have shown improved survival from adding radiation therapy to surgery and chemotherapy in some patient groups, said Dr. Komaki. “A large study by the Radiation Therapy Oncology Group recently found that the addition of radiation in post-surgical stage 3 (microscopic positive mediastinal nodal) disease resulted in a 1-year survival rate of 60% and pushed the 5-year survival rate to 30%.” Dr. Komaki is even more optimistic about the prospect of using radiation with molecularly targeted therapies, particularly EGFR inhibitors. “Preclinical studies have shown EGFRs to be a great sensitizer to radiation—the medication suppresses the tumor’s growth and then the radiation kills it. We think we can eventually add molecularly targeted treatments without causing additional toxicity.” Proton therapy also holds a lot of promise in lung cancer treatment, offering the potential for delivering very high doses of radiation to tumors while avoiding damage to the surrounding organs. Today, lung cancer still holds the dubious distinction of being one of the nation’s top killers. But there is tangible progress against lung cancer, progress that can be seen not just in charts and percentages but in survival. For anyone doing battle with this daunting opponent, “survival” is a word with a very sweet ring.For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, January 2006 issue:
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