Miyamoto Ippei, Kogawa Takahiro, Kurokawa Kana, Miyawaki Eriko, Arihara Yohei, Fukuoka Shota, Ozaki Yukinori, Ono Makiko, Yunokawa Mayu, Yamazaki Masumi, Hayashi Naomi, Fukada Ippei, Ueno Takayuki, Takahashi Shunji, Kitano Shigehisa
Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Gastroenterological Chemotherapy, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Invest New Drugs. 2025 Aug 22. doi: 10.1007/s10637-025-01576-x.
Recently, comprehensive genomic profiling (CGP)-matched therapy and antibody-drug conjugates (ADCs) have garnered increased attention. However, their response rates and prognoses in early-phase clinical trials are not yet widely appreciated in clinical practice. We conducted a retrospective chart review of patients with advanced solid tumors who enrolled in clinical trials as a late-line treatment in our department between January 2020 and December 2023. This study aimed to evaluate clinical outcomes, including overall response rate (ORR), disease control rate (DCR), overall survival (OS), and associated prognostic factors. A total of 574 cases were referred, including 173 in the late-line setting. The ADCs group achieved the highest ORR and DCR (31.9% and 68.1%, respectively). ADCs also demonstrated a longer median progression-free survival (PFS) compared to CGP-matched and other trials (median PFS: ADCs 4.0 months vs. CGP-matched trials 1.9 months vs. others 1.7 months; p = 0.001). Multivariate analysis identified ADCs as significantly associated with improved PFS, while CGP-matched therapy was associated with better OS. The findings suggest that, even in early phase clinical trials for the late-line setting, ADCs can enhance therapeutic responses. These results underscore the need to avoid overreliance on CGP outcomes and instead prioritize early referral to Phase 1 facilities, timely intervention, and the appropriate inclusion of patients to achieve optimal clinical outcomes.
最近，综合基因组分析（CGP）匹配疗法和抗体药物偶联物（ADC）受到了越来越多的关注。然而，它们在早期临床试验中的缓解率和预后在临床实践中尚未得到广泛认可。我们对2020年1月至2023年12月期间在我们科室作为晚期治疗入组临床试验的晚期实体瘤患者进行了回顾性病历审查。本研究旨在评估临床结局，包括总缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）及相关预后因素。共转诊574例患者，其中173例为晚期患者。ADC组的ORR和DCR最高（分别为31.9%和68.1%）。与CGP匹配试验和其他试验相比，ADC的中位无进展生存期（PFS）也更长（中位PFS：ADC为4.0个月，CGP匹配试验为1.9个月，其他试验为1.7个月；p = 0.001）。多变量分析确定ADC与PFS改善显著相关，而CGP匹配疗法与更好的OS相关。研究结果表明，即使在晚期的早期临床试验中，ADC也能增强治疗反应。这些结果强调，需要避免过度依赖CGP结果，而应优先尽早转诊至1期机构、及时干预并适当纳入患者以实现最佳临床结局。
