GlaxoSmithKline (GSK) said it received a positive opinion from the European Medicines Agency (EMEA) recommending marketing authorisation for its oral Hycamtin (topotecan hard capsules). Topotecan capsules will be indicated as monotherapy for the treatment of adult patients with relapsed small cell lung cancer (SCLC) for whom re-treatment with the first-line regimen is not considered appropriate.

Topotecan capsules, once approved, would be the first oral single-agent chemotherapy for the treatment of SCLC after failure of first-line therapy. The intravenous (IV) topotecan requires five consecutive days of IV therapy every three weeks, new topotecan capsules will provide physicians and patients with another, convenient option. The recommended dose of topotecan capsules is 2.3 mg/m2 body surface area/day administered for five consecutive days with a three week interval between the start of each course.
"This positive opinion for topotecan capsules is a significant development for patients with relapsed small cell lung cancer across Europe. Topotecan capsules offer patients a convenient treatment option that has been shown to provide a survival benefit," said Eddie Gray, president, Pharmaceuticals Europe, GlaxoSmithKline. "This approval is yet another example of GSK's continued commitment to researching and developing an industry leading oncology portfolio to address the unmet medical needs of cancer patients around the world."

The positive opinion was based on results from a phase III study comparing topotecan capsules plus best supportive care (BSC) to BSC alone in patients with relapsed SCLC, in addition to results from phase II and phase III supporting studies.

In the pivotal phase III multicentre trial, 141 patients with relapsed SCLC not considered as candidates for standard IV therapy were randomised to receive BSC alone (n=70) or topotecan capsules plus BSC (n=71). Topotecan capsules added to BSC were associated with prolonged survival in patients with relapsed SCLC (p = 0.0104). Median overall survival for topotecan plus BSC was 25.9 weeks (95 per cent CI, 18.3 to 31.6) compared to 13.9 weeks (95 per cent CI, 11.1 to 18.6) for patients who received BSC alone.The hazard ratio was 0.64 (95 per cent C.I: 0.45, 0.90), indicating a 36 per cent reduction in the risk of death for patients who received topotecan capsules plus BSC compared with the patients who received BSC alone.

The most common Grade 3 or 4 haematologic adverse reactions with topotecan capsules were neutropenia, anaemia, and thrombocytopenia. The most common (>10 per cent) non-haematologic adverse reactions (all grades) were nausea, diarrhoea, vomiting, fatigue, and alopecia.

Supportive efficacy and safety data were also provided from a phase II and a phase III study, each of which compared topotecan capsules (oral) directly to topotecan (IV) in patients with relapsed sensitive SCLC.

In the phase III study median survival time was 33.0 weeks (95 per cent CI, 29.1 to 42.4 weeks) in the oral group and 35.0 weeks (95 per cent CI, 31.0 to 37.4 weeks) in the IV group and both treatments were generally well-tolerated. Safety data were presented for the three efficacy studies mentioned above and for an integrated relapsed lung cancer study population of 682 patients. The safety profile was consistent across all four studies.

Lung cancer is the most common cancer in the world attributing to 13.2 per cent of all cancer cases. About 20 out of every 100 cases diagnosed are SCLC. Of all those diagnosed with SCLC, around one in three have limited disease at the time of diagnosis. Two out of three already have extensive disease at the time of diagnosis. Of those who have limited disease and have chemotherapy, between 35 - 40 per cent will be alive two years later. People with extensive disease are also treated with chemotherapy, but unfortunately the survival rate is even lower. Most only survive another ten to twelve months.

Hycamtin (topotecan) is a chemotherapeutic agent that belongs to a class of drugs known as topoisomerase I (topo-I) inhibitors. Topo-I is an enzyme essential for the replication of DNA, and therefore cell division, in both normal and cancer cells. Interaction between topo-I and topotecan results in damage to the cell's cancerous genetic material and the death of dividing cancer cells.