レ点腫瘍学ノート

Top / 日記 / 2022年 / 7月15日

膵癌オラパリブPOLO試験の最終OS

膵癌

皆さんお待ちかね膵癌gBRCAオラパリブのPOLO試験のOSが皆さん大好きなJCOに載りました。

Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer | Journal of Clinical Oncology
PURPOSE The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points. PATIENTS AND METHODS Patients with a deleterious or suspected deleterious germline BRCA mutation whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to active maintenance olaparib (300 mg twice daily) or placebo. The primary end point was PFS; secondary end points included OS, time to second disease progression or death, time to first and second subsequent cancer therapies or death, time to discontinuation of study treatment or death, and safety and tolerability. RESULTS In total, 154 patients were randomly assigned (olaparib, n = 92; placebo, n = 62). No statistically significant OS benefit was observed (median 19.0 v 19.2 months; hazard ratio [HR], 0.83; 95% CI, 0.56 to 1.22; P = .3487). Kaplan-Meier OS curves separated at approximately 24 months, and the estimated 3-year survival after random assignment was 33.9% versus 17.8%, respectively. Median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30 to 0.66; P < .0001), time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89; P = .0111), and time to discontinuation of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63; P < .0001) significantly favored olaparib. The HR for second disease progression or death favored olaparib without reaching statistical significance (HR, 0.66; 95% CI, 0.43 to 1.02; P = .0613). Olaparib was well tolerated with no new safety signals. CONCLUSION Although no statistically significant OS benefit was observed, the HR numerically favored olaparib, which also conferred clinically meaningful benefits including increased time off chemotherapy and long-term survival in a subset of patients.
https://ascopubs.org/doi/abs/10.1200/JCO.21.01604

事前に予想された通り、PFSは伸びてもOSは統計的有意差無し、しかし3年生存率や治療継続期間などは大きく伸びていて、特に3生率17.8→33.9%を見ると逆にOSに差が無いのが不思議な気もする。

PFSはかなり差がついたのにOS有意差が無かったのは、クロスオーバーの多さとかプラセボ群は初回PD後にFOIFIRINOXなりGnPなり後治療にすぐ移ったためかと推測されるけど、そうなると3生率の差が説明つかない気はするが。

「PFS良い+OS有意差なし+HRも大したことない+3生率かなり良い+クロスオーバー多い」から推測されるのは「ICIと同じで、極めて少数の長期奏効者がいる」かつ「ICIと違って、後方ラインでも前方ラインと同じくらい奏効期間がある」ということかしら。。。

そのあと、色々と否定的・懐疑的な意見もあってそちらはこちらにまとめています。

膵癌 膵癌オラパリブPOLO試験の最終OS膵癌 皆さんお待ちかね膵癌gBRCAオラパリブのPOLO試験のOSが皆さん大好きなJCOに載りました。Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olapa
膵癌診療ガイドライン 2019年版 | 日本膵臓学会膵癌診療ガイドライン改訂委員会 |本 | 通販 | Amazon
Amazonで日本膵臓学会膵癌診療ガイドライン改訂委員会の膵癌診療ガイドライン 2019年版。アマゾンならポイント還元本が多数。日本膵臓学会膵癌診療ガイドライン改訂委員会作品ほか、お急ぎ便対象商品は当日お届けも可能。また膵癌診療ガイドライン 2019年版もアマゾン配送商品なら通常配送無料。
https://amzn.to/3yP7Lza