Platinum-free triplet therapy with nab-paclitaxel, S-1, and tislelizumab as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma: a phase II single-arm trial
Mené sur 43 patients atteints d'un adénocarcinome de l'estomac ou de la jonction oesogastrique de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité d'un traitement de première ligne combinant nab-paclitaxel, S-1 et tislélizumab
Background: Platinum-based chemoimmunotherapy is used as a first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma under specific regulatory circumstances, but effectiveness is often limited by cumulative toxicity, particularly in older patients and those with stroma-rich metastases.
Methods: This single-arm, phase II trial evaluated the efficacy and safety of a platinum-free triplet regimen as first-line therapy in patients with metastatic or unresectable G/GEJ adenocarcinoma. Participants received intravenous tislelizumab (200 mg, day 1), nab-paclitaxel (100 mg/m², days 1 and 8), and oral S-1 (80–120 mg twice daily, days 1–14) every 21 days. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints included overall survival (OS), surgical conversion rate, disease control rate (DCR), and safety.
Results: Among 43 enrolled patients, the confirmed ORR was 81.4% (95% confidence interval [CI]: 66.60-91.61%) and the DCR was 90.7% (95% CI: 77.86–97.41%). The overall median PFS was 8.6 months (95% CI: 6.10-11.04), and the overall median OS for the ITT population was 20.1 months (95% CI: 17.69–22.45). In subgroup analyses, patients who underwent conversion surgery had significantly longer OS compared with those who did not (median 29.5 months vs. 18.3 months; hazard ratio [HR]: 0.42, 95% CI: 0.20–0.90; P = 0.050). Patients aged ≥ 65 years showed longer PFS (13.7 vs. 7.2 months; HR: 0.39, 95% CI 0.19–0.80; P = 0.006) and OS (29.2 vs. 16.4 months; HR: 0.42, 95% CI 0.20–0.88; P = 0.021) than those aged < 65 years. Eight patients (18.6%) underwent conversion surgery, with 2 achieving pathological complete response. Grade ≥ 3 treatment-related adverse events included neutropenia (9.3%), leukopenia (7.0%), and anemia (2.3%).
Conclusions: This triplet regimen of nab-paclitaxel, S-1, and tislelizumab showed encouraging antitumor activity with a manageable safety profile. These findings warrant further validation in phase III randomized controlled trials, and support this regimen as a potential strategy, especially for older patients who may be less tolerant of platinum-based therapies.
BMC Cancer , article en libre accès, 2026