Lung Cancer Patients Living Longer With Targeted Drugs

Avastin is one of a new class of drugs that works by targeting the newly formed blood vessels that develop around tumors, a process called antiangiogenesis. Recent studies have seen positive survival results in colon cancer and now lung cancer.

Originally approved by the Food and Drug Administration (FDA) for colon cancer, Avastin is a monoclonal antibody that inhibits the vascular endothelial growth factor (VEGF), a protein essential in the angiogenesis process. The drug prevents the growth of new vessels to the tumor by binding to VEGF, which in turn prevents VEGF from binding to its receptor site on the cell’s surface. By blocking this mechanism, Avastin essentially starves the tumor of its blood and oxygen supply.

Roy Herbst, MD, chief of thoracic oncology at M.D. Anderson Cancer Center in Houston, calls it a breakthrough in lung cancer therapy.

“It’s now being shown to enhance chemotherapy and improve survival for colorectal cancer and now lung cancer,” says Dr. Herbst. “I think it’s going to become a new standard of care in front-line lung cancer for patients who were treated on the protocol, which includes patients with non-squamous lung cancer, which is about 70 to 80 percent of lung cancer patients.”

Preliminary analysis from a phase III trial of Avastin with standard combination chemotherapy (paclitaxel/carboplatin) for lung cancer shows an improvement in survival in patients with non-small-cell lung cancer (NSCLC) when compared with chemotherapy alone. Patients with non-squamous NSCLC who were treated with Avastin plus cytotoxic chemotherapy had an overall survival of 12.5 months, an improvement of 2.3 months over Taxol (paclitaxel)/Paraplatin (carboplatin) alone.

“Two months is extraordinary,” says Dr. Herbst, who predicts the one-year survival rate for Avastin will be upwards of 40 to 50 percent for non-squamous NSCLC patients. “Time to progression is probably going to be much higher, too.”

This study represents the first antiangiogenic therapy combined with cytotoxic chemotherapy that has shown a survival advantage over chemotherapy alone in untreated lung cancer patients. Full study results are eagerly awaited at the annual meeting of the American Society of Clinical Oncology in Orlando this May.

Side effects of Avastin include life-threatening bleeding in the lungs, an adverse effect not seen when it was being evaluated for colon cancer. Patients with squamous cell lung cancer in their proximal airways appear to be more susceptible to this side effect than patients with adenocarcinoma. These relatively infrequent side effects were believed to be secondary to the tumor location in the central airways in addition to their histology.

Clinical trials researching the role of Avastin in various solid tumors are under way in combination with other targeted agents such as Tarceva. “We now know that we can combine Avastin with Tarceva and use a cocktail of targeted therapies in patients,” Dr. Herbst says.

In an earlier phase I/II trial, Avastin was paired with Tarceva, another targeted therapy that inhibits the epidermal growth factor receptor. It is believed that since the two drugs attack different pathways used in cancer growth, the combination would be more effective than either therapy alone. Side effects were minimal and included rash and diarrhea, which is commonly seen with Tarceva. Twenty percent of patients had a response to the combination and the median survival time was 12.6 months.

“Avastin really gives new hope for patients with lung cancer,” Dr. Herbst says. “We might not be curing advanced lung cancer—though I wish it would—but at least we may turn it into a disease that people can live with it, like a chronic disease.”

Other cancers that Avastin is being researched for are ovarian, pancreatic, prostate, kidney and breast. Preliminary results were announced in mid-April on a phase II/III trial involving breast cancer patients. Although an improvement in survival was not proven in this trial, patients taking Avastin and paclitaxel saw a four-month improvement in disease-free progression compared with patients taking paclitaxel alone. Results of this trial will be announced at this year’s ASCO meeting. Genentech is planning a larger Avastin trial to specifically test survival in breast cancer patients in the near future.

For more information about lung cancer treatments, read the Summer 2005 issue of CURE.

Editor's Note: Avastin was approved by the Food and Drug Administration for metastatic lung cancer on October 11, 2006.