Arigami Takaaki, Matsushita Daisuke, Shimonosono Masataka, Hirase Yuki, Tsuruda Yusuke, Sasaki Ken, Baba Kenji, Kawasaki Yota, Ohtsuka Takao
Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Sci Rep. 2025 Mar 31;15(1):10961. doi: 10.1038/s41598-025-95501-0.
The CheckMate 649 trial demonstrated the clinical benefit of nivolumab plus chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer. However, the background discrepancy between clinical practice and randomized controlled trials may impact the therapeutic strategy and prognosis of patients. This study aimed to assess the clinical significance of eligibility criteria determined by the CheckMate 649 trial and identify prognostic factors in clinical practice. A total of 160 patients with HER2-negative metastatic gastric cancer who underwent chemotherapy were retrospectively enrolled and classified into two groups based on eligibility criteria. Among the 160 patients, 76 (47.5%) and 84 (52.5%) were included in the eligible and ineligible groups, respectively. The ineligible group had a significantly lower induction of second- and third-line chemotherapy than the eligible group (P = 0.02 and P = 0.02, respectively). The median overall survival in the eligible and ineligible groups was 22.9 and 10.5 months, respectively, with the ineligible group having a significantly poorer prognosis than the eligible group (P < 0.01). Responders to first-line chemotherapy had a better prognosis than non-responders in both groups (P = 0.01 and P < 0.01, respectively). Multivariate analyses identified disease control as an independent prognostic factor in both groups (P < 0.01 and P < 0.01, respectively). Patients with a poor general condition who fulfilled the ineligibility criteria as determined using randomized controlled trials are included in clinical practice, and these criteria are related to tumor response and prognosis.
CheckMate 649试验证明了纳武利尤单抗联合化疗对人表皮生长因子受体2（HER2）阴性晚期胃癌患者的临床益处。然而，临床实践与随机对照试验之间的背景差异可能会影响患者的治疗策略和预后。本研究旨在评估CheckMate 649试验确定的纳入标准的临床意义，并确定临床实践中的预后因素。本研究回顾性纳入了160例接受化疗的HER2阴性转移性胃癌患者，并根据纳入标准将其分为两组。在这160例患者中，符合纳入标准组和不符合纳入标准组分别有76例（47.5%）和84例（52.5%）。不符合纳入标准组二线和三线化疗的诱导率显著低于符合纳入标准组（分别为P = 0.02和P = 0.02）。符合纳入标准组和不符合纳入标准组的中位总生存期分别为22.9个月和10.5个月，不符合纳入标准组的预后明显比符合纳入标准组差（P < 0.01）。两组中一线化疗有反应者的预后均优于无反应者（分别为P = 0.01和P < 0.01）。多因素分析确定疾病控制在两组中均为独立的预后因素（分别为P < 0.01和P < 0.01）。临床实践中纳入了根据随机对照试验确定的不符合纳入标准的一般状况较差的患者，这些标准与肿瘤反应和预后相关。
