Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3)

Shi, Yuankai; Wu, Lin; Yu, Xinmin; Xing, Puyuan; Wang, Yan; Zhou, Jianying; Wang, Airong; Shi, Jianhua; Hu, Yi; Wang, Ziping; An, Guangyu; Fang, Yong; Sun, Sanyuan; Zhou, Caicun; Wang, Changli; Ye, Feng; Li, Xingya; Wang, Junye; Wang, Mengzhao; Liu, Yunpeng; Zhao, Yanqiu; Yuan, Ying; Feng, Jifeng; Chen, Zhendong; Shi, Jindong; Sun, Tao; Wu, Gang; Shu, Yongqian; Guo, Qisen; Zhang, Yi; Song, Yong; Zhang, Shucai; Chen, Yuan; Li, Wei; Huang, Niu; Hu, Wenwei; Wang, Lijun; Huang, Jianan; Zhang, Yang; Cheng, Ying; Wu, Zhengdong; Peng, Bo; Sun, Jiya; Mancao, Christoph; Wang, Yanqi; Sun, Luyao

doi:10.1002/cac2.12385

Cited by 23 publications

(16 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As demonstrated in previous studies conducted over the last 20 years, only around 5% of patients treated with first‐line chemotherapy would experience progression‐free survival at 18 months of treatment; however, this proportion could rise to 25%–40% for chemo plus IO regimen 2,3,34–46 ; Similarly, chemotherapy alone in a later‐line setting could only yield around 5% progression‐free survival at 12‐months of treatment 23,24,47–49 . Based on these data, our expert panel suggested that it is reasonable to set the cutoff value of PFS at 18 months (first‐line setting) and 12 months (later‐line setting).…”

Section: Clinical Definition Of Secondary Resistance To Immunotherapy...mentioning

confidence: 62%

Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer

Huang,

Lin,

Chu

et al. 2023

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

show abstract

Section: Clinical Definition Of Secondary Resistance To Immunotherapy...mentioning

confidence: 62%

Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer

Huang,

Lin,

Chu

et al. 2023

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…A flowchart demonstrating how studies were identified and included is shown in Figure 1. Finally, 34 articles [9–42] were included in this meta-analysis (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…RATIONALE 307 [24] 1 Squamous NSCLC PD-1 Tislelizumab + Chem (120) Chem (121) 218 23 8.6 (8.1-9.0) ORIENT-3 [25] >1 Squamous NSCLC PD-1 Sintilimab(145) Chem (135) 258 22 23.56 (0.03-34.30) ORIENT-11 [26] 1 NSCLC PD-1 Sintilimab + chem (266) Chem (131) 303 94 8.9 ORIENT-12 [27] 1 Squamous NSCLC PD-1 Sintilimab + chem (179) Chem (178) 327 30 8.0 (0.5-12.6) CHOICE-01 [28] 1 NSCLC PD-1 Toripalimab + chem (309) Chem (156) 377 88 16.2 ASTRUM-005 [29] 1 SCLC PD-1 Serplulimab + chem (389) Chem (196) 481 104 12.3 (0.2-24.8) IMpower110 [30] 1 NSCLC PD-L1 Atezolizumab (107) Chem (98) 143 62 15.7 (0-35) IMpower130 [31] 1 Nonsquamous NSCLC PD-L1 Atezolizumab + chem (451) Chem ( 228) 400 279 19.2 (15.4-23.0) IMpower [32] >1 Squamous NSCLC PD-L1 Atezolizumab + chem (343) Chem (340) 557 126 18.1 IMpower [33] >1 Nonsquamous NSCLC PD-L1 Atezolizumab + chem (292) Chem (286) 384 194 28.4 IMpower [34] 1 Nonsquamous NSCLC PD-L1 Atezolizumab + BCP (356) BCP (336) 425 267 9.5 OAK [35] >1 NSCLC PD-L1 Atezolizumab (425) Chem (425) 520 330 21 JAVELIN Lung 200 [36] >1 NSCLC PD-L1 Avelumab (396) Chem (396) 367 162 34.7 (0.03-44.4) PACIFIC [37] >1 NSCLC PD-L1 Durvalumab (473) Placebo (236) 500 213 25.2 (0.2-43.1) MYSTIC [38] 1 NSCLC PD-L1 Durvalumab (163) Chem (162) 219 106 30.2 (0.3-37.2) POSEIDON [39] 1 NSCLC PD-L1 Durvalumab plus chem (338) Chem(337) 501 174 34.9 (0.0-44.5) CAPSTONE-1 [40] 1 SCLC PD-L1 Adebrelimab (230) Placebo (232) 372 90 13.5 (8•9-20•1) GEMSTONE-301 [41] 1 NSCLC PD-L1 Sugemalimab (255) Placebo (126) 351 30 14.3 (6.4-19.4) GEMSTONE-302 [42] 1 CheckMate 017 [9] 0.59 (0.44-0.79); <0.001 0.57 (0.41-0.78) 0.67 (0.36-1.25) 0.62 (0.47-0.81); <0.001 0.63 (0.46-0.85) 0.71 (0.40-1.26) CheckMate 026 [10] 1.02 (0.80-1.30); NA 0.97 (0.74-1.26) 1.15 (0.79-1.66) 1.15 (0.91-1.45); 0.25 1.05 (0.81-1.37) 1.36 (0.98-1.90) CheckMate 057 [11] 0.73 (0.59-0.89); 0.002 0.73 (0.56-0.96) 0.78 (0.58-1.04) 0.92 (0.77-1.11); 0.39 0.81 (0.63-1.04) 1.04 (0.80-1.37) TASUKI-52 [12] 0.85 (0.63-1.14); 0.2754 NA NA 0.56 (0.43-0.71); <0.0001 0.53 (0.41-0.69) 0.72 (0.45-1.15) KEYNOTE 010 [13] 0.70 (0.61-0.80); NA 0.71 (0.60-0.86) 0.66 (0.53-0.84) 0.84 (0.73-0.96); NA NA NA KEYNOTE 024…”

Section: Quality Assessmentmentioning

confidence: 99%

The effect of gender on the clinical outcome of PD-1/PD-L1 inhibitor in advanced lung cancer patients

Wu,

Sun,

Sun

et al. 2023

Medicine

View full text Add to dashboard Cite

Background: Programmed death protein-1/ligand-1 (PD-1/L1) inhibitors have widely used in the treatment of lung cancer. Some literatures indicated that different gender might not have equal immune response, but no agreement have reached on the issue. Hence, we performed a systematic review and meta-analysis that examine the effect of gender on the clinical outcome of PD-1/PD-L1 inhibitor in advanced lung cancer patients. Methods: Related database and conferences were searched. Studies that reported the relationship between gender and the overall survival (OS) or progression-free survival (PFS) of PD-1/L1 inhibitor were included. Meta-analysis was conducted to obtain pooled hazard ratios (HRs) with 95% CI. Results: We included 34 studies with 11,883 lung cancer patients. Meta-analysis showed that PD-1/PD-L1 inhibitors significantly prolonged the OS (males: HR 0.71, 95%CI 0.66–0.77; females: HR 0.72, 95%CI 0.63–0.82) and PFS (males: HR 0.60, 95%CI 0.55–0.66; females: HR 0.72, 95%CI 0.62–0.84) versus chemotherapy. The clinical benefit (OS HR: 0.99; PFS HR: 0.83) was not statistically significant between males and females. In patients treated with cemiplimab, male patients had a better OS (0.53, 95%CI 0.42–0.66) and PFS (OS 1.51, 95%CI 0.80–2.82) compared with female patients, but the small number of female patients precludes us from drawing any firm conclusions in female subpopulations. Conclusion: The clinical benefit of PD-1/PD-L1 inhibitors was not statistically significant between males and females during the treatment of lung cancer. In the future, researchers who are designing new immunotherapy studies should ensure a larger inclusion of women in trials, to avoid erroneously extending to women results that are obtained mainly in male patients.

show abstract

“…In the meanwhile, patients with PD-L1 TPS≥1% in OAK research ( 19 ), a phase 3 clinical research with atezolizumab, had a median OS of 15.7 months compared to 10.3 months when compared to docetaxel. In the ORIENT-3 study ( 20 ), the median PFS was also much longer in the sintilimab group, coming in at 4.30 months compared to 2.79 months in the docetaxel group. The RATIONALE303 study ( 21 ) was designed to evaluate the efficacy and safety of tislelizumab versus docetaxel in second or later-line treatment of patients with advanced NSCLC, showing a median PFS of 4.1 months vs. 2.6 months and a PFS rate of 23.3% vs. 5.7% at 12 months.…”

Section: Discussionmentioning

confidence: 99%

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study

et al. 2022

View full text Add to dashboard Cite

BackgroundThe aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer.MethodsIn this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents’ group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox’s proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis.ResultsThe average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group.ConclusionPD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

show abstract

Sintilimab versus docetaxel as second‐line treatment in advanced or metastatic squamous non‐small‐cell lung cancer: an open‐label, randomized controlled phase 3 trial (ORIENT‐3)

Cited by 23 publications

References 48 publications

Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer

Clinical definition of secondary resistance to immunotherapy in non‐small cell lung cancer

The effect of gender on the clinical outcome of PD-1/PD-L1 inhibitor in advanced lung cancer patients

PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study

Contact Info

Product

Resources

About