Highlighting Advances in Lung Cancer

World Conference on Lung Cancer Convenes in Korea

Lung cancer is the second most common cancer and the most common cause of cancer-related death in both men and women in the US. The National Cancer Institute estimates there will be more than 213,000 cases of lung cancer this year, resulting in more than 160,000 deaths. The overall mortality rate lung cancer rose steadily through the 1980s and peaked around 1990. Although incidence and mortality rates for men have dropped over the past decade, a similar trend has not occurred in women. Mortality rates are greatest among African-American males, followed by white males.

Given these grim statistics, lung cancer remains one of the most researched diseases in the oncology community. There is a strong and ongoing effort to develop new and effective treatments for patients with non—small cell lung cancer (NSCLC) as well as those with small-cell lung cancer (SCLC).

The 12th World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC), was held in early September in Seoul, Korea. The world’s top lung cancer specialists convened at the WCLC to present and discuss the latest research in this disease. Key themes included accurate targets, new combinations of drugs to reduce toxicity, and strategies to improve outcomes.

Giorgio Scagliotti, MD, Department of Clinical & Biological Sciences, University of Turin, Italy and an IASLC director, explained the focus of the meeting. “While we are focusing on the search for improved detection and prevention methods for lung cancer, it continues to be paramount that we improve the options we can provide patients who are already diagnosed. We hope that the findings from these studies will continue to support patient needs—specifically, reducing the toxicities associated with cancer therapy and improving overall survival rates.”

Recent Advances in Targeted Therapy

Key presentations on targeted therapy included exciting new data on cetuximab (Erbitux), gefitinib (Iressa), and erlotinib (Tarceva).

Thomas Lynch, MD, Massachusetts General Hospital, Boston, MA presented findings from the FLEX trial—a multicenter Phase III study of cetuximab in combination with taxane/carboplatin vs. taxane/carboplatin alone as a first-line treatment in 676 patients with advanced NSCLC. Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR) pathway and indirectly promotes programmed cell death. The combination regimen significantly improved overall survival compared with taxane/carboplatin alone.

Oncologists are tailoring therapies to individual patient needs to effectively fight the disease, while managing potential side effects and toxicities, particularly in elderly patients. For example, the results of a Phase II, open-label, parallel-group study comparing gefitinib—an agent that specifically targets the EGFR—with vinorelbine in chemotherapy-naive elderly patents with locally advanced or metastatic NSCLC were presented by Dr. Lucio Crino, Silvestrini Hospital, Perugia, Italy. Gefitinib was comparable to vinorelbine in terms of progressionfree survival, overall survival, and overall response rate, but was better tolerated than vinorelbine.

Today’s research focuses on markers that may influence the patient’s response to therapy and overall survival. Erlotinib, an orally active inhibitor of EGFR tyrosine kinase, has been shown to improve survival rates and quality of lifein previous studies. Dr. E. H. Tan, Department of Medical Oncology, National Cancer Center, Singapore General Hospital, Singapore, presented the results of the multicenter, Phase II, open-label MERIT study, which was performed to identify molecular markers that may be predictive for clinical benefit with erlotinib. MERIT is the largest prospective RNA expression profiling study ever conducted in second-line NSCLC. Results from the 264 patients evaluable for efficacy support the use of erlotinib as an effective alternative to chemotherapy for patients with advanced NSCLC. An objective response was seen in 36 patients (13.6%), and 83 patients (31.4%) had clinical benefit. Median overall survival was 7.6 months; median progression-free survival was 11.3 weeks. The most common adverse events were rash, diarrhea, dyspnea, and anorexia.

Darbepoetin Alfa Study Shows No Negative Impact on Survival in SCLC

At the World Conference on Lung Cancer, Amgen presented the results from the so-called “145 Study”—a randomized, double-blind, placebo-controlled, Phase III study evaluating the efficacy and safety of darbepoetin alfa (Aranesp) in previously untreated patients with extensive-stage SCLC who are receiving chemotherapy. The study demonstrated no statistically significant difference in risk of death or investigator assessed progression-free survival between darbepoetin alfa and placebo.

The study is a component of Amgen’s ongoing pharmacovigilance program, designed to evaluate the effect of Aranesp on long-term survival in anemic patients undergoing concomitant chemotherapy. The study was completed 3 months ahead of Amgen’s post-marketing commitment; results were announced previously and primary data were provided to the FDA.

As reported previously, the “145 Study” demonstrated that darbepoetin alfa maintained hemoglobin levels at a greater level than placebo and significantly reduced the need for red blood cell transfusions relative to placebo. The estimated difference in hemoglobin change between the two groups was 0.84 g/dL. A total of 52 patients (17%) in the darbepoetin alfa group had at least one red blood cell transfusion during the study, compared with 116 patients (39%) in the placebo group.

Pfizer Oncology Initiates Global Phase III Trial to Evaluate Sunitinib in Combination with Erlotinib in Advanced NSCLC

Pfizer announced at the World Conference on Lung Cancer the initiation of a global Phase III clinical trial to evaluate the efficacy and safety of sunitinib (Sutent) in combination with erlotinib (Tarceva) in previously treated patients with advanced NSCLC.

The large, randomized, double-blind trial of 956 patients is designed to compare the overall survival of patients taking sunitinib plus erlotinib, with that of those taking erlotinib plus placebo. Pfizer added that secondary endpoints of the study include progression-free survival, objective response rate, 1-year survival, duration of response, adverse events, and patient-reported outcomes

According to Dr. Keunchil Park, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, Korea, “This Phase III trial is investigating the potential benefit of the multi-kinase inhibitor sunitinib, combined with an EGFR inhibitor, erlotinib, in the treatment of advanced lung cancer. Survival rates in lung cancer continue to be low in comparison with other cancers despite currently available treatments. It is our hope that this approach will provide an option for patients fighting advanced lung cancer.”