2011 Top Game Changers in Oncology

Counting Down: Game Changers 10 Through 6

In 2011, great progress was made in the science and management of a variety of cancers. Our Medscape commentators selected and ranked the top 10 game changers in oncology for 2011. Here are their selections.

10. New Regimen Improves Outcomes in Neuroblastoma

A provocative European study^[1] showed improved outcomes in high-risk neuroblastoma using a high-dose myeloablative regimen. Until now, the best outcome in neuroblastoma has hovered around the 50% survival threshold, but the new regimen tested has pushed this up to 60%. European investigators say this regimen should be the new standard of care. "This is an incredible success and a great achievement for pediatric oncology," said Julie Park, MD, from Seattle Children's Hospital in Washington, who acted as discussant for the study.

The results are important for patients with this extremely difficult-to-treat disease," said principal investigator Ruth Ladenstein, MD, MBA, Associate Professor of Pediatrics at the University of Vienna, Austria.

Treatment for neuroblastoma comprises several steps. It begins with intense upfront chemotherapy to induce remission (induction) and is followed by surgery and radiation, myeloablative therapy with stem cell transplantation, and then consolidation therapy with 13-cis-retinoic acid and immunotherapy, if available.

The European trial used an induction regimen known as rapid COJEC, which consists of both cisplatin and carboplatin, and then compared a high-dose myeloablative regimen known as BuMel (busulphan plus melphalan) with carboplatin, etoposide, and melphalan (control group).

The BuMel group led to significantly improved survival at 3 years compared with the control group (60% vs 48%). "The superiority was based on a lower relapse rate," noted Dr. Ladenstein.

Read the complete Medscape News article on this trial, which was presented during the plenary sessions of the 2011 American Society for Clinical Oncology (ASCO®) annual meeting.

9. A Shooting Gallery of Targets in Lung Cancer

The treatment of non-small cell lung cancer (NSCLC) is undergoing a revolution driven by a greater understanding of the genetic factors fueling this disease. In personalized therapy, drugs are chosen according to the mutations found in the patient's tumor rather than chemotherapy chosen for the organ where the tumor is located.

Contributing to the growing knowledge of genetic targets is a landmark study by the Lung Cancer Mutation Consortium (LCMC),^[2] which involves 14 centers across the United States. The LCMC conducted a prospective study in which lung cancer tissue was assessed using a multiplex assay that identified 10 known driver mutations. In addition to EGFR and ALK, they are testing for KRAS, HER2, BRAF, PIK3CA, AKTI, MEKI, NRAS, and MET. Many of these mutations have targeted agents under development or, in the case of HER2, have targeted drugs already on the market (trastuzumab and lapatinib, which are used in breast cancer). The results so far show that 54% of the tested tumor samples have single-driver mutations. This information is now being used to select patients for first-line therapy with erlotinib or to place these patients into clinical trials with experimental targeted therapies specifically directed at their tumor mutation.

"Although an individual driver mutation may have a single-digit percentage incidence, when you look at all of the possible mutations that exist in lung cancer, you are likely to find a mutation," said Mark G. Kris, MD, lead author and Chief of Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York City, in a Medscape commentary. "Even in individuals who did not have a mutation that would suggest a certain clinical trial, we knew what treatments not to give those patients." This study, Dr. Kris added, "brings us one step closer to our goal of personalized medicine."

View the complete commentary by Mark G. Kris, MD, and read the original Medscape News story on this trial, which was reported at the 2011 ASCO® annual meeting.

8. Strongest Data Ever for ER-Positive Breast Cancer

The combination of everolimus plus exemestane produced "the strongest data ever seen in estrogen receptor [ER]-positive breast cancer," principal investigator José Baselga, MD, from the Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News. The pivotal phase 3 study, known as BOLERO-2,^[3]was stopped early because of the benefit observed. Results were unveiled at the 2011 European Multidisciplinary Cancer Congress (EMCC).

"Everolimus is the most important advance in breast cancer since trastuzumab," said Fabrice André, MD, PhD, from the Institut Gustave Roussy, Paris, France, who acted as discussant. "The data are robust and are clinically relevant," he said, adding that "the efficacy is in the range of the most important recent advances in the field of medical oncology."

Everolimus is an mTOR inhibitor that has already been approved in the United States for the treatment of progressive neuroendocrine tumors of pancreatic origin and advanced renal cell carcinoma in certain patients. Exemestane is an aromatase inhibitor that is already widely used as adjuvant therapy for ER-positive breast cancer. Both drugs are taken orally.

Read the complete Medscape News story on this trial.

7. Extended Adjuvant Treatment Improves Survival in GIST

Extended adjuvant treatment with imatinib improves survival in patients with high-risk gastrointestinal stromal tumors (GIST). Imatinib administered for 3 years improved both relapse-free survival and overall survival in patients after surgery, compared with 1 year of adjuvant treatment.^[4]

Previous data showed that initiating adjuvant imatinib therapy reduces the risk for GIST recurrence compared with placebo. "But the effect of imatinib on overall survival is not known," said lead author Heikki Joensuu, MD, Professor of Oncology at Helsinki University Central Hospital in Finland, who presented the findings during the plenary session here at the ASCO® 2011 annual meeting.

The 5-year relapse-free survival in patients was higher in those who received 3 years of treatment than in those who received 1 year (65.6% vs 47.9%; hazard ratio [HR], 0.46; P < .0001). The 5-year overall survival was also better in patients who received 3 years of therapy (92.0% vs 81.7%; HR. 0.45; P = .019).

Kathy Miller, MD, Chair of the scientific program for the 2011 ASCO® annual meeting, said in a Medscape commentary, "There had been a lot of debate in the GIST community that perhaps the drug was so effective in people with metastatic disease that you didn't really need to give adjuvant therapy for a longer time or maybe you didn't need to give it at all. You could just catch up and treat these folks when they recurred, and that was definitely not true. A longer duration of therapy, 3 years instead of 1, improved survival."

"We are looking at 92% in the 3-year group, and that is very high," said Dr. Joensuu. "We are making substantial improvement here."

View the complete commentary by Kathy D. Miller, MD, and read the original Medscape News story on this trial.

6. New Hope for Patients With Refractory Lymphoma

The experimental agent brentuximab vedotin, which has shown strong responses in patients with resistant and refractory Hodgkin lymphoma, was the first drug approved for lymphoma in 30 years. The results were reported at the 52nd annual meeting of the American Society of Hematology by Robert Chen, MD, Assistant Professor at the City of Hope National Medical Center in Duarte, California.^[5] The data come from a single-group multicenter study of 102 patients, all of whom had failed autologous stem cell transplantation and a median of 4 chemotherapy regimens (range, 1-13). The median age of patients was 31 years (range, 15-77 years).

Brentuximab 1.8 mg/kg was administered as a 30-minute outpatient intravenous infusion once every 3 weeks for up to 16 cycles of therapy (median, 9 cycles).

Responses were "dramatic," Dr. Chen said. The objective response rate was 75%, and tumor reduction was demonstrated in 94 patients (96%). Around one third of patients (34%) achieved complete remission.

In August, the US Food and Drug Administration (FDA) granted accelerated approval of brentuximab vedotin infusion for the treatment of relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, as reported at the time by Medscape.

"Why are we so excited about this?" asked Bruce D. Cheson, MD, Professor of Medicine, Georgetown University, Washington, DC, in a Medscape commentary. "Not only is this a great drug, it is also a proof of concept. We now have demonstrated that you can take an antibody and link it strongly to a poison. It will get in the cells and kill them, without doing much damage to the rest of the body. This will be one of many to follow in its footsteps."

View the complete commentary from Bruce D. Cheson, MD, and read the original Medscape News story.

Medscape Oncology © 2011  WebMD, LLC

Cite this: Bruce D. Cheson, David J. Kerr, Mark G. Kris, et. al. 2011 Top Game Changers in Oncology - Medscape - Nov 23, 2011.