Department of Maternal and Child Health and Urological Sciences, Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy
Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Int J Gynecol Cancer. 2023 Sep 4;33(9):1448-1457. doi: 10.1136/ijgc-2023-004740.
Poly(ADP-ribose) polymerase inhibitors (PARPi) have sculpted the current landscape of advanced ovarian cancer treatment. With the advent of targeted maintenance therapies, improved survival rates have led to a timely interest in exploring de-intensified strategies with the goal of improving quality of life without compromising oncologic outcomes. The emerging concept of systemic treatment de-escalation would represent a new frontier in personalizing therapy in ovarian cancer. PARPi are so effective that properly selected patients treated with these agents might require less chemotherapy to achieve the same oncologic outcomes. The fundamental key is to limit de-escalation to a narrow subpopulation with favorable prognostic factors, such as patients with -mutated and/or homologous recombination-deficient tumors without macroscopic residual disease after surgery or other high-risk clinical factors. Potential de-escalation strategies include shifting PARPi in the neoadjuvant setting, de-escalating adjuvant chemotherapy after primary debulking surgery, reducing PARPi maintenance therapy duration, starting PARPi directly after interval debulking surgery, omitting maintenance therapy, and continuing PARPi beyond oligoprogression (if combined with locoregional treatment). Several ongoing trials are currently investigating the feasibility and safety of de-escalating approaches in ovarian cancer and the results are eagerly awaited. This review aims to discuss the current trends, drawbacks, and future perspectives regarding systemic treatment de-escalation in advanced ovarian cancer.
聚（ADP-核糖）聚合酶抑制剂（PARPi）已经重塑了晚期卵巢癌治疗的现状。随着靶向维持治疗的出现，生存率的提高引发了人们对探索去强化策略的及时兴趣，目的是在不影响肿瘤学结果的情况下提高生活质量。系统治疗降级的新兴概念将代表卵巢癌个体化治疗的一个新前沿。PARPi 非常有效，经过这些药物治疗的适当选择的患者可能需要更少的化疗就能达到相同的肿瘤学结果。关键是将降级限制在具有有利预后因素的狭窄亚人群中，例如手术后存在 -突变和/或同源重组缺陷肿瘤且无肉眼残留疾病的患者，或存在其他高危临床因素的患者。潜在的降级策略包括在新辅助治疗中使用 PARPi、在初次肿瘤细胞减灭术（PDS）后降级辅助化疗、减少 PARPi 维持治疗的持续时间、直接在间隔肿瘤细胞减灭术（IDS）后开始 PARPi、省略维持治疗以及在寡进展（如果与局部区域治疗联合）后继续使用 PARPi。目前正在进行的几项试验正在研究在晚期卵巢癌中降级方法的可行性和安全性，结果备受期待。本文旨在讨论晚期卵巢癌系统治疗降级的当前趋势、缺点和未来展望。
