固体腫瘍における早期薬剤開発:国立がん研究所が主催する第1相試験の分析
Dai Chihara1, Ruitao Lin2, Christopher R Flowers3
1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Medical Oncology Service, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lancet (London, England)
|August 14, 2022
まとめ
癌の第1段階試験における反応率は,死亡率が増加することなく20年間でほぼ倍増しました. 併用療法と特定の薬剤は改善された結果を示したが,がんの種類による異質性は,患者による情報に基づいた決定を必要としている.
科学分野:
- 腫瘍学
- 臨床試験
- ガン治療薬
背景:
- 癌の第1段階試験は,臨床的利益の期待が歴史的に低いため,参加と研究進歩を阻害する可能性があります.
- 1期固体腫瘍試験における応答と毒性の傾向に関する包括的なデータは限られている.
- がん治療薬の開発の進歩により 治療反応が改善されたのかもしれません
研究 の 目的:
- 固体腫瘍のフェーズ1臨床試験における毒性および応答率の傾向を評価する.
- 試験結果に対する異なる治療戦略 (単独療法 vs. 併用療法) と薬剤クラスの影響を分析する.
- 様々な癌の反応率に影響を与える要因を特定する.
主な方法:
- NCIが主催した固体腫瘍のフェーズ1試験 (2000年−2019年) の患者レベルのデータの分析.
- 治療に関連した死亡,治療中の死亡,グレード3〜4の毒性,および異なる研究期間における全体的な応答率の評価.
- 時間の経過による傾向,がんのタイプ特有の反応,患者特異との関連性,登録期間,薬剤,試験設計の評価.
主要な成果:
- 治療関連死亡率 (0. 7%) は有意な変化なし,全体的な反応率は9. 6% (2000 - 05) から18. 0% (2013 - 19) に増加した.
- 併用療法 (15. 8%) は単独療法 (3. 5%) よりも著しく高い応答率を示した.
- 膀,乳がん,腎臓がん,メラノーマでは有意な改善が見られたが,臓がんと結腸がんでは有意な変化は見られなかった.
結論:
- 治療に関連した死亡率が上昇することなく,フェーズ1試験の反応率は20年間でほぼ2倍になりました.
- 癌の種類,試験薬,試験設計によって,反応の有意な異質性がある.
- 1期試験への参加を検討している患者にとって,情報に基づいた意思決定は極めて重要です.
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