A cornerstone of Aptium Oncology is an overriding dedication to advancing cancer care through leading-edge clinical research. Beyond making a meaningful difference in the lives of current cancer patients, this research is shaping the future of cancer treatment. Aptium’s participation in the Annual Meeting of the American Society of Clinical Oncologists (ASCO), which unites international oncology professionals in addressing their challenges and opportunities, underscores our common purpose of enhancing oncologists’ knowledge--and, in turn, improving high-quality cancer care.

Several significant findings were reported at the recent 44th Annual ASCO Meeting. Held in Chicago from May 30-June 3, 2008, the conference was themed ldauo;One Community: Innovating Patient Care.” Regarded as the premier educational and scientific event in the oncology community, the conference brought together physicians, researchers and other health care professionals from around the world to present the latest information about cancer research, prevention, care and treatment.

“The ASCO presentations provided a number of meaningful clinical advances in oncology treatments,” says John Macdonald, M.D., Chief Medical Officer, Aptium Oncology. “Many of these studies broke new ground, while others confirmed previous findings. Notably, a majority of the new research points to the future of personalized medicine; using the right drug for the right patients for the right tumor--and at the right time.”

Predicting Patient Benefits from Colorectal Cancer Treatment
Noting that, historically, clinicians defined cancers by their sites of origin, for example breast or lung or colon, Dr. Macdonald says that the current focus is increasingly on the cancer’s molecular makeup. “We’re learning, for example, that all colon cancers are not the same,” he says, citing a study by Eric Van Cutsem, Professor of Internal Medicine at the University of Leuven, Belgium. Dr. Van Cutsem looked at the molecular biologic configuration of colorectal cancers in order to determine appropriate drug use. The study also underscores the importance of routinely testing a patient’s genetic status to determine if a patient’s KRAS gene contains mutations. The presence of KRAS mutations is considered a strong predictor that a patient won’t respond to drugs like cetuximab and panitumumab, which are epidermal growth factor receptor (EGFR) inhibitors and block the protein that helps cancer grow and multiply.

The good news is that through routine KRAS testing of all colorectal cancer patients immediately following diagnosis, clinicians can identify those patients who will benefit from EGFR-directed therapy, as well as those who won’t. For the 40-50 percent of colorectal cancer patients who are KRAS-mutation positive, test findings will allow physicians to spare their patients the expense and toxicities of therapies that will not be effective. At the same time, the study points to a significant advantage in using cetuximab for those patients without KRAS mutations.

Improving Pancreatic Cancer Survival
Dr. Macdonald cites the final results of the CONKO-001 (Charité Onkologie Clinical Studies in Gastrointestinal Cancer) study as another noteworthy ASCO conference presentation. The study’s extended follow-up confirms early findings from the CONKO trial published last year in the Journal of the American Medical Association (JAMA. 2007;297:267-277), while providing statistically significant results for overall survival.

Previous results showed that treatment with the drug gemcitabine increases the amount of time a patient is free of cancer. While gemcitabine has been the standard therapy for patients with advanced pancreatic cancer that can’t be operated on, the goal of CONKO-001 was to determine if gemcitabine increases survival in pancreatic patients who have had surgery, as rates of local recurrence remain high.

Study author Ulf P. Neumann, MD, PhD, from the Charité University Medical School, in Berlin, Germany, noted that treatment with gemcitabine doubled the overall survival rate for patients following pancreatic cancer sugery and should be considered the standard of care in the postoperative setting.

These research findings represent the first large randomized study to suggest an advantage in postoperative administration of gemcitabine with conclusive results demonstrating improvement in both overall--and disease-free--survival.

Progress in Multiple Myeloma
Advances in Small Cell Lung Cancer Treatment
“It was exciting to hear so much progress being made in the treatment for multiple myeloma, and that it is capturing broad attention from researchers,rdquo; says Brian Durie, M.D, Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute. Also Senior Advisor for Hematologic Malignancies and National Program Director for Multiple Myeloma and Related Disorders for Aptium Oncology, Dr. Durie cites a presentation by S. Vincent Rajkumar, M.D., and Associate Professor of Medicine at the Mayo Clinic.

Dr. Rajkumar presented continuing results of a Phase 3 trial coordinated by the Eastern Cooperative Oncology Group comparing the use of lenalidomide (REVLIMID®) plus high-dose dexamethasone, versus lenalidomide plus low-dose dexamethasone (one day per week) in patients with newly diagnosed multiple myeloma. Study findings showed the somewhat paradoxical result that the overall two-year survival rate was 10 percent higher (88 percent) in the group receiving low-dose dexamethasone in contrast to the group that received high-dose dexamethasone. The higher dosages of dexamethasone are more toxic and ultimately less effective.

Results of a landmark analysis of ongoing results were also presented by Dr. Rajkumar. Conducted after the completion of four cycles of lenalidomide-dexamethasone, the analysis showed equal 93 percent two-year survival for both those patients who continued lenalidomide plus low-dose dexamethasone therapy, as well as for those who went on to transplant. This result raises the tantalizing question as to the need for or benefit from the autotransplant.

Dr. Durie also cites another study presented by Paul Richardson, M.D., Clinical Director, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston, Massachusetts. Dr. Richardson’s examination of the safety and effectiveness for patients of a three-drug combination--lenalidomide, bortezomib and dexamethasone--showed the regime to be very active and well tolerated in patients newly diagnosed with multiple myeloma.

“The results of Dr. Richardson’s Phase 2 study were spectacular (98% response rate),” says Dr. Durie, who is currently comparing results of the Eastern Oncology Group’s study to Dr. Richardson’s research in a larger, randomized Phase 3 Southwest Oncology Group (SWOG) trial comparison. His objective is to determine if the three-drug combination is more effective than the two drugs.

“The introduction of these new drugs is so promising that they could supersede the need for myeloma patients to have stem cell transplants,” continues Dr. Durie. “These drugs are novel agents that target the active pathways for the disease. Cancer is very crafty,’ he adds. “While these new drugs are not 100 percent selective, they broadly shut down the cancer’s main pathways, as well as back up pathways.”

Dr. Durie further notes that, unlike past chemotherapy treatments, these new drugs are extremely well tolerated. “Increasingly, my patients are able to remain very active while being treated for myeloma,” he says. “They’re working in their professions and leading rich, productive lives.”

Results of a South West Oncology Group (SWOG) Phase 3 randomized study comparing two drug regimes for extensive stage small cell lung cancer were presented by Ronald Natale, M.D., Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute. Dr. Natale, who is also Director of the National Lung Cancer Research Program and Senior Research Advisor for the Solid Tumor Program for Aptium Oncology, says the new study was designed to confirm or refute a Japanese study published in 2002 and presented at ASCO seven years ago. SWOG study objectives included a comparison of survival rates for patients treated with the drugs cisplatin and irinotecan versus a regimen of cisplatin and etoposide.

“The results of the SWOG study are a stark contrast to the survival benefit reported in the Japanese trial and further address the role of irinotecan in small cell lung cancer,” says Dr. Natale, noting there were several possible explanations as to why the SWOG trial didn’t confirm the survival rates reported by the Japanese. “Most likely, the discrepancy includes pharmacogenics, in that each individual’s genetics affect the body’s response to the drugs. Ultimately, we can conclude that etoposide remains the reference standard for treating small cell lung cancer.”

Other significant clinical advances in small cell lung cancer treatment, according to Dr. Natale, include a randomized Phase 3 trial of 1,125 patients from 30 countries. Researchers looked at adding cetuximab (Erbitux)--a targeted therapy that blocks the EGFR protein--to chemotherapy with cisplatin (Platinol) and vinorelbine (Navelbine) for newly diagnosed advanced non-small cell lung cancer patients. In contrast to the current standard treatment for these patients, study results showed that patients who received Erbitux lived slightly longer than 11 months, in comparison to 10 months for patients who received only chemotherapy--establishing Erbitux, combined with chemotherapy, a new standard in treating non-small cell lung cancer patients.

The Future of Cancer Treatment
“If we look back to 1995, prior to the new drugs, a patient with advanced metastasized colon cancer had 12-13 months to live,” says Dr. Macdonald. “Now, 13 years later, it’s more like 30 months, and we have every reason to believe that these rates will continue to improve. The same is true for a number of other cancers, such as breast cancer, where we also have better and more targeted treatment options, allowing people to live longer and with good quality of life.”

As for the future of cancer treatment, Dr. Macdonald says it is a bright one, with oncologists embracing the personalized medicine model for all cancers. And the promising new treatments presented at this year’s ASCO Annual Meeting are only the beginning of a new era of targeted therapies that will continue to improve care, ease discomfort and enhance quality of life for cancer patients everywhere.