Pemetrexed Plus Cisplatin Has "Remarkable" Results in Mesothelioma

Martha Kerr

October 07, 2008

October 7, 2008 (Berlin, Germany) — Investigators announced the findings from phase 3 studies, which found that cisplatin plus an antifolate — either pemetrexed or raltitrexed — increase survival in patients with mesothelioma nearly 3-fold.

The latest findings from a number of trials were announced here at the European Respiratory Society 2008 Annual Congress by Thierry Berghmans, MD, from the department of intensive care and thoracic oncology at Institut Jules Bordet, in Brussels, Belgium.

Two of the largest randomized trials involved nearly 500 patients with mesothelioma. In the first, 250 patients were randomized to either a combination of cisplatin plus raltitrexed or to cisplatin alone. In the other, 243 patients with mesothelioma were randomized to pemetrexed plus cisplatin or to cisplatin monotherapy.

Cisplatin was considered the best treatment option before the advent of the antifolate agents, Dr. Berghmans commented.

Progression-free survival was 5.7 months in the cisplatin-plus-pemetrexed group and 3.9 months in the cisplatin-monotherapy group, a difference that was highly statistically significant (P = .001), Dr. Berghmans said. Median survival time was 12.1 months with combination therapy and 9.3 months with monotherapy (P = .02). Overall risk reduction was 41.3% with pemetrexed plus cisplatin and was 18.7% with cisplatin alone (P < .001).

In the second trial presented at a press conference by Dr. Berghmans, first-line treatment with raltitrexed plus cisplatin was associated with a progression-free survival of 5.3 months, compared with 4 months for treatment with cisplatin alone (P = .06). One-year survival was 46.2% with and 39.6% without raltitrexed. "The numbers show a trend in favor of raltitrexed," Dr. Berghmans noted.

Even pemetrexed as second-line therapy improves survival, Dr. Berghmans said in an interview with Medscape Pulmonary Medicine after his presentation.

Disease control occurred in 59.3% of patients in the pemetrexed-plus-cisplatin group, compared with 19.2% in the cisplatin-monotherapy group (P < .0001). Time to progression was 3.7 months with pemetrexed as second-line therapy and 1.5 months with supportive care alone (P = .0002). "The figures are highly statistically significant," Dr. Berghmans said.

"Cisplatin plus pemetrexed is the best treatment we've got for mesothelioma," Dr. Berghmans asserted. "There is a positive response with a shrinking of tumor size."

Surgery plus cryostatics plus radiotherapy is currently under investigation as another option, and it has shown promise in the first few patients. "These are highly selected, younger patients with less-advanced disease," the Belgian researcher said.

"This is really remarkable progress in treatment," said conference moderator Gunnar Hillerdal, MD, from the Karolinska Lung Clinic, in Stockholm, Sweden.

"We are also making progress in diagnoses, with immunohistochemical studies. We're making diagnoses earlier, when it is a little bit easier to manage the disease. . . . We are also getting better at identifying etiology. There is a hereditary familial component in addition to exposure to mineral fiber, such as asbestos."

"A decade ago, mesothelioma was considered a hopeless disease, with a mean survival time of 6 months. That is no longer the case," Dr. Hillerdal said during closing remarks.

Dr. Berghmans' studies were funded in part by Lilly Oncology, Ltd, which manufactures pemetrexed under the brand name Alimta. Dr. Hillerdal has disclosed no relevant financial relationships.

European Respiratory Society (ERS) 2008 Annual Congress: Poster P2636, Symposium. Presented October 7, 2008.


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