Sintilimab plus docetaxel as second-line therapy of advanced non-small cell lung cancer without targetable mutations: a phase II efficacy and biomarker study.
Sintilimab plus docetaxel as second-line therapy of advanced non-small cell lung cancer without targetable mutations: a phase II efficacy and biomarker study.
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DOI：
10.1186/s12885-022-10045-0
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发表时间：
2022-09-05
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
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Single-agent immunotherapy is currently the recommended second-line therapy for patients with advanced non–small cell lung cancer (NSCLC) without targetable mutations; however, the objective response rate (ORR) remains low. This phase II study evaluated the efficacy of the combination therapy of sintilimab plus docetaxel and explored potential biomarkers for efficacy prediction. Thirty patients with NSCLC without targetable mutations whose disease progressed from first-line platinum-based chemotherapy from October 2019 to December 2020 were enrolled in this single-arm, single-center, phase II trial. Sintilimab (200 mg) and docetaxel (75 mg/m2) were administered every 3 weeks until progression. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarker analyses of blood and tissue samples were also performed. Among 30 patients, 11 patients had partial response, resulting in an ORR of 36.7%. The median PFS was 5.0 months (95%CI: 3.9–6.1) and OS was 13.4 months (95%CI: 5.6–21.2). The most common immune-related adverse event of any grade was hepatitis, observed in 23.3% (7/30) of patients. Treatment-emergent adverse events were manageable. Patients detected with high PD-L1 expression in circulating tumor cells (cutoff value ≥32.5% based on the median CTC-PD-L1 expression) achieved significantly higher ORR (60% versus 13.3%, p = 0.021) and significantly longer median PFS (6.0 versus 3.5 months, p = 0.011) and median OS (15.8 versus 9.0 months, p = 0.038) than those with low CTC-PD-L1 level. Patients detected with PD-L1 < 1% and CD8 ≥ 1% expression from their baseline tissue samples had significantly higher ORR (83.3% versus 12.5%, p = 0.026) but similar PFS (p = 0.62) and OS (p = 0.15). This study demonstrated the effectiveness and safety of sintilimab plus docetaxel as a second-line treatment of NSCLC without targetable mutations after progression from first-line platinum-based chemotherapy. This study was registered in the Clinical trials registry with ClinicalTrials.gov Identifier NCT03798743 (SUCCESS). The online version contains supplementary material available at 10.1186/s12885-022-10045-0. • Survival outcomes of patients with NSCLC without targetable mutations remain depressing. • Sintilimab plus docetaxel as second-line therapy improves progression-free survival outcomes. • Sintilimab plus docetaxel is safe and well-tolerated. • Patients detected with high PD-L1 expression in circulating tumor cells (≥32.5%, median level in 30 patients) achieved significantly higher ORR, PFS and OS. • Patients detected with PD-L1 < 1% and CD8 ≥ 1% expression from their baseline tissue samples had significantly higher ORR (p = 0.026). The online version contains supplementary material available at 10.1186/s12885-022-10045-0.
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DOI：
10.1200/jco.20.01605
发表时间：
2021-03-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Borghaei H;Gettinger S;Vokes EE;Chow LQM;Burgio MA;de Castro Carpeno J;Pluzanski A;Arrieta O;Frontera OA;Chiari R;Butts C;Wójcik-Tomaszewska J;Coudert B;Garassino MC;Ready N;Felip E;García MA;Waterhouse D;Domine M;Barlesi F;Antonia S;Wohlleber M;Gerber DE;Czyzewicz G;Spigel DR;Crino L;Eberhardt WEE;Li A;Marimuthu S;Brahmer J
通讯作者：
Brahmer J
影响因子：
20.4
作者：
Lee, Jiyun;Koh, Jiae;Ahn, Myung-Ju
通讯作者：
Ahn, Myung-Ju
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
11.5
作者：
Hoy, Sheridan M.
通讯作者：
Hoy, Sheridan M.
影响因子：
3.6
作者：
Dall'Olio, Filippo G.;Gelsomino, Francesco;Ardizzoni, Andrea
通讯作者：
Ardizzoni, Andrea