ALK-NSCLCにおけるcrizotinibの高い有効性

新たなALK阻害薬は特異的なALK遺伝子変異を有する進行非小細胞肺がん患者において有効性を示した

Novel ALK inhibitor shows high response rate in patients with advanced non-small cell lung cancer with specific ALK gene alteration

第46回ASCOのプレナリーセッションで取り上げられたスタディの結果、ある特異的なALK遺伝子の再構成を有する進行肺がん患者の多くに、治験薬crizotinibを用いた治療が有効であることが示された。ALK遺伝子が他の遺伝子と融合すると、未分化リンパ腫キナーゼ、つまりALK（がん細胞の増殖や発育に不可欠な酵素）と呼ばれる腫瘍特異蛋白の産生を暗号化し肺がんの成長を促進する。経口投与薬であるcrizotinibはALK酵素を阻害することにより有効性を発揮する。肺がん患者の5%がこのALK遺伝子変異を有すると推定されている。今回のスタディは進行非小細胞肺がん患者（ほとんどが腺がんを有し非喫煙者または元喫煙者）に対するcrizotinibの有効性を評価した。全ての患者がALK遺伝子融合を有していた。Crizotinibを投与された患者のほとんど（8週後に時点で87%）において、今日までにこの治療が奏効し、腫瘍の縮小や疾患の安定化が認められた。腫瘍の縮小が認められたのは、これらのうちの57%であった。治療期間中央値は約6ヵ月であった。Crizotinibと標準的なセカンドライン化学療法を比較するphase III無作為化試験が開始されている。

An expanded Phase I clinical trial finds that the large majority (approximately 90 percent) of patients with advanced non-small cell lung cancer (NSCLC) with a specific form of the ALK responded to treatment with the investigational ALK inhibitor, crizotinib (PF-02341066), and more than half of these patients experienced tumor shrinkage.

"Many of these patients had received three or more prior treatments, and we would expect only about 10 percent to respond," said lead author Yung-Jue Bang, M.D., Ph.D., professor in the Department of Internal Medicine at Seoul National University College of Medicine in Seoul, Korea. "These results are quite dramatic, and represent an important improvement over what we would see with standard chemotherapy for patients with metastatic disease."

When the ALK gene fuses with another gene, it promotes lung cancer cell growth by encoding the production of a tumor-specific protein called anaplastic lymphoma kinase, or ALK -an enzyme that is critical for the growth and development of cancer cells. Crizotinib, which is taken orally, works by inhibiting the ALK enzyme. About one in 20 lung cancer patients in the United States are estimated each year to be diagnosed with ALK-positive NSCLC.

The study assessed crizotinib in patients with NSCLC, most of who had adenocarcinoma and were nonsmokers or former smokers. All of the patients had the ALK gene fusion.

Nearly all patients (87 percent at 8 weeks) who received crizotinib to date responded to this treatment and experienced tumor shrinkage or disease stabilization. Among those, 57 percent had tumor shrinkage. The median duration of treatment was approximately six months. A randomized, Phase III trial (PROFILE-1007) has begun, comparing crizotinib to standard second-line chemotherapy.

Disclosures: Yung-Jue Bang, Consultant or Advisory Role, Pfizer, Honoraria, Pfizer, Research Funding, Pfizer; Eunice Kwak, Research Funding, Pfizer; Alice Shaw, Honoraria, Pfizer, Research Funding, Pfizer; D. Camidge, Research Funding, Pfizer; A. Iafrate, Honoraria, Pfizer, Research Funding, Pfizer; Robert Maki, Research Funding, Pfizer; Benjamin Solomon, Research Funding, Peter MacCallum Cancer Center, Pfizer; Sai-Hong Ou, Research Funding, Pfizer; Ravi Salgia, Research Funding, Pfizer.