Priority review granted for oral formulation of HYCAMTIN (topotecan)

GlaxoSmithKline (GSK) has announced that its new drug application (NDA) for ORAL HYCAMTIN (topotecan) capsules, a treatment for relapsed small cell lung cancer (SCLC), has been granted Priority Review by the United States Food and Drug Administration (FDA).

This application was based on encouraging results from a Phase III study comparing ORAL HYCAMTIN plus best supportive care (BSC) to BSC alone in patients with relapsed SCLC, in addition to two Phase II and Phase III supporting studies. The data from the pivotal Phase III trial were published in the December 1, 2006 issue of the Journal of Clinical Oncology. BSC refers to treatments intended to control, prevent and relieve disease complications to improve comfort and quality of life for the patient, but are not intended to have any anti-tumor effects.

"Small cell lung cancer is an aggressive cancer for which there are limited treatment options. We are encouraged that the FDA has agreed to consider ORAL HYCAMTIN for the treatment of patients with this devastating illness," said Debasish Roychowdhury, M.D., Vice President, Global Clinical Development, Oncology Medicine Development Center (MDC), GSK. "Today's FDA filing acceptance is another important milestone in GSK's continuing efforts to develop treatment options to meet the medical needs of cancer patients and the physicians who treat them."

About 15% of patients with lung cancer have SCLC, an aggressive and fast growing form of the disease. The data evaluating ORAL HYCAMTIN that was submitted to the FDA demonstrated a survival benefit for patients with relapsed SCLC. In this Phase III clinical trial, ORAL HYCAMTIN added to BSC was associated with prolonged survival and improvements in common symptoms found in patients with relapsed SCLC. This was the first randomized study ever to demonstrate that patients with relapsed SCLC live longer when they are treated with chemotherapy.

Unlike IV HYCAMTIN, which requires five consecutive days of intravenous therapy every three weeks, ORAL HYCAMTIN will allow patients to be treated at home. If approved by the FDA, ORAL HYCAMTIN will be the only oral single- agent chemotherapeutic drug approved for the treatment of SCLC after failure of first-line therapy. ORAL HYCAMTIN is not currently approved for patients with SCLC in any country.

"The evaluation of an oral treatment is a crucial step towards helping SCLC patients maintain a higher quality of life," said John Eckardt, M.D., Director of Clinical Research for the Center for Cancer Care and Research, St. Louis, MO. "Given the heritage of IV HYCAMTIN, the prospect of offering a new, convenient therapeutic option for SCLC that can be taken at home and may prolong survival is exciting."

In the Phase III multicenter trial, 141 patients with relapsed SCLC not considered as candidates for standard IV therapy were randomized to receive BSC alone (n = 70) or ORAL HYCAMTIN (2.3 mg/m2/day, days 1 through 5, every 21 days) plus BSC (ORAL HYCAMTIN; n = 71). The primary endpoint of overall survival was prolonged in the ORAL HYCAMTIN group. Median survival with ORAL HYCAMTIN plus BSC was 25.9 weeks (95% CI, 18.3 to 31.6) and was 13.9 weeks (95% CI, 11.1 to 18.6) with BSC alone (log-rank P = .0104). In addition, patients who received ORAL HYCAMTIN plus BSC showed a consistent trend towards greater symptom control and a slower worsening of overall health status compared to BSC alone.

Principal toxicities with ORAL HYCAMTIN were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing ORAL HYCAMTIN with BSC, infection greater than or equal to grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9% and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the ORAL HYCAMTIN arm. All-cause mortality within 30 days following random assignment was 13% on BSC and 7% on ORAL HYCAMTIN.

SCLC is caused by an uncontrolled growth of cells beginning on the surface of the lung's breathing tubes (called bronchi) and tends to spread widely through the body. This is important because it means that surgery is rarely used as a treatment option. Chemotherapy is the most common treatment for all stages of SCLC. Although SCLC is often responsive to first-line treatments, patients may relapse at any stage.

SCLC is most common in current or past smokers, but can also be caused by environmental risk factors such as exposure to radon and air pollution.