卵巣がんにおける無増悪生存期間の倍加（Abstract # LBA5002）

プラチナ抵抗性卵巣がんに対する化学療法にベバシズマブを併用することにより無増悪生存期間が改善する

Adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer improves progression-free survival

プラチナ抵抗性卵巣がん女性の第3相無作為化トライアルにおいて、標準的な化学療法にベバシズマブを併用することにより無増悪生存期間（PFS）が倍になったとの結果が第48回American Society of Clinical Oncology学会において発表された。この多施設国際スタディでは、最終のプラチナ製剤投与後6か月以内に増悪を認めた上皮性卵巣がん、卵管がんまたは原発性腹膜がん患者361人に対し、ベバシズマブ併用化学療法と化学療法単独を比較した。全ての患者がこの状況で通常提案される3つの標準的な化学療法―週1回のパクリタキセル、topotecan、またはペグ化リポソームドキソルビシン―のうちのいずれかを受けていた。追跡期間中央値13.5か月後、ベバシズマブ併用化学療法群患者の75%（179人中135人）において再発が認められたのに対し、化学療法単独群患者におけるその割合は91%（182人中166人）であった。PFS中央値は併用群で6.7か月であり、単独群では3.4か月であった。全生存期間に関するデータはまだ出揃っていない。有害事象発現率はベバシズマブ群において高かった。有害事象はグレード2を超える高血圧（20%対7%）、蛋白尿（11%対1%）、消化管穿孔（2%対0）、消化管瘻または膿瘍（2%対0）などであった。

Adding bevacizumab to standard chemotherapy doubled progression-free survival (PFS) in a phase III randomized trial of women with platinum-resistant ovarian cancer according to a study presented at the American Society of Clinical Oncology's 48th Annual Meeting.

"These results are very significant because the addition of bevacizumab offers a new treatment option for the 20 percent of women who have primary platinum-resistant disease, as well as those whose disease later becomes platinum-resistant," said lead study author Eric Pujade-Lauraine, M.D., Ph.D., professor, Université de Paris Descartes, France and head of the Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), a clinical trials cooperative group based in France. "For the first time in platinum-resistant ovarian cancer, we have been able to significantly improve progression-free survival with a combination therapy."

The multi-center international randomized study evaluated bevacizumab added to chemotherapy vs. chemotherapy alone in 361 patients with epithelial ovarian, fallopian tube or primary peritoneal cancer with disease progression within six months of their last dose of platinum therapy. All patients received one of three standard chemotherapy drugs normally offered in this setting—weekly paclitaxel, topotecan or liposomal pegylated doxorubicin. These treatments are equally effective in treatment for resistant ovarian cancer, differing only in their toxicities. The investigators selected the chemotherapy based on each patient's previous experience with the drugs.

After a median follow-up of 13.5 months, 75 percent (135 of 179) of the patients who received bevacizumab in addition to chemotherapy had a recurrence, compared to 91 percent (166 of 182) who received chemotherapy alone.

Median PFS was 6.7 months in the combination group, compared to 3.4 months in the chemotherapy alone group. Overall survival data is not yet complete.

Adverse events were higher in the bevacizumab group. These included greater than Grade 2 hypertension (20 percent vs. 7 percent), proteinuria (11 percent vs. 1 percent), gastrointestinal perforations (2 percent vs. 0), and fistula or abscesses (2 percent vs. 0). For other adverse events greater than Grade 3, the study arms were equivalent.

Strict patient selection—based on the absence of history of bowel obstruction/abdominal fistula or clinical/radiological evidence of rectosigmoid involvement—helped to limited the incidence of adverse events due to bevacizumab, Dr. Pujade-Lauraine said.

Previous studies have shown that bevacizumab is active in first-line and second-line treatment of ovarian cancer. Future studies are likely to test when and how long to treat the disease with this agent.