肺がんに対する維持療法は無増悪生存期間を改善する（Abstract No. CRA7510）

ペメトレキセドによる維持療法を拡大することにより進行肺がん患者の無増悪生存期間が改善する

Extending pemetrexed treatment as maintenance therapy improves progression-free survival in patients with advanced lung cancer

2011年ASCOで発表されたPhase III無作為化トライアルの結果、化学療法薬ペメトレキセドを用いた維持療法により、初回化学療法の一部としてもペメトレキセド投与を受けた進行非扁平上皮非小細胞肺がん患者の無増悪生存期間（PFS）が改善することが示された。PARAMOUNTは、非常に難治性の非小細胞肺がん患者の無増悪生存期間を維持療法の継続により上昇させうることを示した初めての大規模トライアルである。このスタディにおいて939人の患者が、ペメトレキセドおよびシスプラチンを用いて疾患の寛解導入を試みる標準的な4コースのファーストライン寛解導入療法を受けた。これらの患者のうちがんが進行しなかった患者539人がペメトレキセド維持療法および最適な支持療法を受ける群（359人）またはプラセボと最適な支持療法を受ける群（180人）に無作為に割り付けられた。最適な支持療法とは、例えば疼痛や感染症を軽減したり食欲を刺激したりするなどの非抗がん療法である。ペメトレキセド維持療法により疾患進行リスクが38%低下した（p=0.00025）。PFS中央値はペメトレキセド群で4.1ヵ月であったのに対しプラセボ群では2.8ヵ月であった。疾患コントロール率はペメトレキセド群で71.8%であったのに対しプラセボ群では59.6%であった（p=0.009）。

A Phase III, randomized trial showed that maintenance therapy with the chemotherapy drug pemetrexed (Alimta) improves progression-free survival (PFS) in patients with advanced nonsquamous non-small cell lung cancer who also received pemetrexed as part of their initial chemotherapy regimen. PARAMOUNT is the first large trial to demonstrate that continuation maintenance can increase progression-free survival in advanced non-small cell lung cancer, an extremely difficult disease to treat. The study provides physicians with a new treatment option after first-line therapy with pemetrexed.

"Cisplatin-pemetrexed therapy is an effective induction therapy for advanced disease. But after the fourth course, we typically stop treatment, and eventually need to go to a second-line therapy when the disease progresses again," said lead author Luis Paz-Ares, M.D., Ph.D., chair of oncology at Seville University Hospital in Seville, Spain. "This cancer doesn't have many treatment options, and we don't want to fire all of our treatment bullets at once. These results suggest that patients can still continue to benefit from the use of the same drug. This could change the standard of care for these patients, at least in terms of maintenance treatment."

In the study 939 patients were given the standard four courses of first-line induction treatment with pemetrexed and cisplatin to attempt to induce disease remission. Of those, 539 patients whose cancer did not progress were randomized to maintenance pemetrexed and best supportive care (359) or placebo and best supportive care (180) until disease progression. Best supportive care entails non-anti-cancer therapy, including treatment to reduce pain and infections, for example, and stimulate appetite.

The investigators found that pemetrexed maintenance resulted in a 38 percent reduction in the risk of disease progression. The median PFS was 4.1 months for those in the pemetrexed group compared to 2.8 months in the placebo group. The disease control rate was 71.8 percent in the pemetrexed arm compared to 59.6 percent on placebo.

The toxicity profile of maintenance therapy was very favorable and in accordance with previous single agent pemetrexed.

Maintenance therapy isn't mandatory for every patient, Dr. Paz-Ares noted. "Some may have significant toxicity during induction treatment, and it may be worth having a treatment break. On the other hand, a patient who is having a good response in the absence of significant toxicity may be a good candidate for maintenance therapy. A lot of factors go into the treatment decision, and each patient should be informed."