LBA56 ORIENT-12: Sintilimab plus gemcitabine and platinum (GP) as first-line (1L) treatment for locally advanced or metastatic squamous non-small-cell lung cancer (sqNSCLC)

Zhou, Caicun; Wu, Lin; Fan, Yun; Wang, Zhaoguang; Liu, L.; Chen, G.; Zhang, L.; Huang, Dingzhi; Cang, Shundong; Yang, Zhijian; Zhou, Jianying; Li, B.; Li, J.; Fan, Min; Zhang, W.; Yang, Wei; Wang, S.; Zhou, Hui

doi:10.1016/j.annonc.2020.08.2289

Cited by 15 publications

(18 citation statements)

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“…According to the study screening process in Figure 1, 20 RCTs were eligible for our NMA, including 13,032 patients and 17 different treatments. They are SICI regimens, including PEM (7,8,36), CEM (10), NIV (37), ATE (9), and DUR (28); SICI+CT regimens, including PEM+CT (11)(12)(13)(14)(15)(16), sintilimab (SIN)+CT (19,20), ATE+CT (21)(22)(23)(24), IPI+CT (25,26), camrelizumab (CAM) +CT (18), and NIV+CT (17); DICI regimens, including DUR +TRE (28) and NIV+IPI (27,38); DICI+CT regimens, including DUR+TRE+CT (28,30) and NIV+IPI+CT (29); and CT as control group, including CT with maintenance with pemetrexed (Mpem) and platinum-based doublet CT. The baseline characteristics of the studies were shown in Table 1.…”

Section: Study Characteristics Of Network Meta-analysismentioning

confidence: 99%

“…For patients with a low expression of PD-L1, SICI plus CT (SICI+CT) showed better efficacy. KEYNOTE 021 (11,12), KEYNOTE 189 (13,14), KEYNOTE 407 (15,16), CheckMate 227 part2 (17), CAMEL (18), , and ORIENT-12 (20) evaluated the efficacy of PD-1 inhibitors in combination with platinum-based CT and obtained significant benefits. However, great differences exist in the efficacy of anti-PD-L1 or CTLA-4 antibodies combined with CT in randomized controlled trials (RCTs) such as IMpower 130 (21), IMpower 131 (22), IMpower 132 (23,24), Govindan (25), and Lynch (26).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Zhang

Hao

et al. 2021

Front. Immunol.

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BackgroundImmune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC) significantly, but few studies compared single ICI (SICI)-based treatments and double ICIs (DICI)-based treatments. We summarized the general efficacy of ICI-related treatments, compared the efficacy and safety of SICI-based [programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors ± chemotherapy (CT)] and DICI-based (PD-1/PD-L1 inhibitors+CTLA-4 inhibitors ± chemotherapy) treatments vs. CT in the first-line treatment.MethodsWe included phase II/III randomized controlled trials (RCTs), including patients with histologically confirmed stage IIIB–IV driver-gene wild-type NSCLC who received first-line ICI-related therapy in at least one arm. PubMed, Embase, and Cochrane Library were searched from January 1, 2005, to December 31, 2020. This network meta-analysis was performed in a Bayesian framework using GEMTC and JAGS package in R.3.6.1. The research was registered with PROSPERO (CRD42020184534).ResultsTwenty RCTs were involved, including 13,032 patients and 17 treatment regimens. The results showed that ICI-based therapies could provide a pooled median overall survival (mOS) (POS) of 15.79 (95% CI: 14.85–16.73) months, and there were no significant differences in OS, progression-free survival (PFS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) between DICI-based treatments (POS: 14.81, 12.11–17.52 months) and SICI-based treatments (POS: 16.17, 14.59–17.74 months) in overall patients. However, DICI-based treatments had significantly prolonged the OS over SICI-based treatments in squamous and PD-L1 <1% subgroups. The ranking of OS benefit by Bayesian surface under the cumulative ranking curve (SUCRA) spectrum showed that DICI+chemotherapy ranked first for overall population and subgroups including squamous, non-squamous, any level of PD-L1 expression, smoking, male, Eastern Cooperative Oncology Group performance status (ECOG PS) = 0/1, age < 65/≥65 while SICI+CT for low tumor mutation burden (TMB), non-smoking, and female subgroups, and DICI for high TMB subgroups.ConclusionsIn the first-line therapy for advanced wild-type NSCLC, both SICI- and DICI-based treatments could bring significant overall advantages over chemotherapy, with comparable outcomes of efficacy and ≥3AEs. DICI-based treatments were more effective than SICI-based treatments in squamous and PD-L1 <1% subgroups. For most populations, DICI+chemotherapy could be the best choice with a survival benefit, while SICI+chemotherapy has established its position actually.Systematic Review Registration[PROSPERO], identifier [CRD42020184534].

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Section: Study Characteristics Of Network Meta-analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Zhang

Hao

et al. 2021

Front. Immunol.

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“…This lack of survival benefit in high PD-L1 expression tumour could be explained as 51% of patients in control arm received ICI at the time of progression, 42% receiving pembrolizumab, and the efficacy of pembrolizumab in second-line setting is higher in tumours with high PD-L1 expression [3]. More recently, in the ORIENT-12 trial performed in Asian patients with squamous advanced NSCLC, the combination of sintilimab plus platinum-gemcitabine chemotherapy improved the outcome (PFS, HR 0.53; p<0.001 and OS, HR 0.57, p=0.017) compared with chemotherapy [27]. Finally, the IMpower 131 trial [31], testing atezolizumab plus chemotherapy in squamous NSCLC patients did not improve the overall survival compared with chemotherapy alone, except for the subgroup of patients with high PD-L1 expression.…”

Section: Pd-l1 and Chemo-immunotherapy Combinations In Nsclcmentioning

confidence: 99%

“…All these trials have reported overall survival benefit with ICIs compared with platinum-based chemotherapy (table 1). This survival benefit occurred: 1) in trials testing ICIs as monotherapy in selected patients whose tumours expressed PD-L1 (KEYNOTE-024 [15], KEYNOTE-042 [16]); IMPOWER 110 [17] and EMPOWER-Lung 1 [18]); 2) in trials enrolling unselected patients and testing ICIs in combination with -other ICIs, such as anti-CTLA4 agents (CheckMate 227 [19,20], testing nivolumab plus ipilimumab) -chemotherapy, in non-squamous (KEYNOTE-189 [21], IMpower130 [22], IMpower150 [23,24], ORIENT-11 [25]) and in squamous histologies (KEYNOTE-407 [26], ORIENT-12 [27]) -other ICIs and chemotherapy (CheckMate 9LA [28], testing nivolumab and ipilimumab plus 2 cycles of platinum-based chemotherapy according histologic subtype).…”

Section: Introductionmentioning

confidence: 99%

The efficacy of immune checkpoint inhibitors in thoracic malignancies

2021

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The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm for multiple cancer types, including thoracic malignancies. In advanced non-small cell lung cancer (NSCLC), ICIs have shifted treatment paradigm and improved overall survival reaching almost one-third of patients alive at 5 years. ICIs therapies have also modified the therapeutic strategy in first-line setting in metastatic small-cell lung cancer (SCLC) patients as well as in malignant pleural mesothelioma (MPM) improving the overall survival compared with standard treatment. This phenomenon is of huge relevance as both SCLC and MPM were considered orphan diseases without any significant improvement in the therapeutic strategy in the first-line setting during the last 15 years. In this review, we aim to review the efficacy of ICI in thoracic malignancies either in monotherapy or in combination, according to predictive biomarkers, and to the US Food and Drug Administration and the European Medicines Agency approvals of treatment strategies. We address the efficacy of these agents, especially in NSCLC according to PD-L1 expression and histologic subtype.

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“…Given the above preclinical and clinical data, we conducted a prospective, multicenter, single-arm, phase II trial assessing the safety and e cacy of triple combination of Sintilimab, a PD-1 inhibitor which had been proven to be effective in advanced NSCLC [28,29], SBRT and GM-CSF as second-line therapy in sensitizing driver mutation negative metastatic NSCLC. In order to determine the tolerability of this novel triple combination therapy, a safety run-in phase was conducted by monitoring the dose-limiting toxicities (DLTs) in the rst 20 enrolled patients and herein we reported the results.…”

Section: Introductionmentioning

confidence: 99%

Sintilimab, Stereotactic Body Radiotherapy and Granulocyte-macrophage Colony Stimulating Factor as Second-line Therapy for Advanced Non-small Cell Lung Cancer: Safety Run-in Results of a Multicenter, Single-arm, Phase II Trial

Zhou

et al. 2021

Preprint

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Objectives: The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment. Materials and Methods: Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8Gy x 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research. Results: Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n=11), mediastinal lymph node (n=5), liver (n=1), abdominal lymph node (n=1), pleural nodule (n=1) and vertebra (n=1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed. Conclusion: Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration: ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC - Tabular View - ClinicalTrials.gov

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LBA56 ORIENT-12: Sintilimab plus gemcitabine and platinum (GP) as first-line (1L) treatment for locally advanced or metastatic squamous non-small-cell lung cancer (sqNSCLC)

Cited by 15 publications

References 0 publications

Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Comparison of Efficacy and Safety of Single and Double Immune Checkpoint Inhibitor-Based First-Line Treatments for Advanced Driver-Gene Wild-Type Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

The efficacy of immune checkpoint inhibitors in thoracic malignancies

Sintilimab, Stereotactic Body Radiotherapy and Granulocyte-macrophage Colony Stimulating Factor as Second-line Therapy for Advanced Non-small Cell Lung Cancer: Safety Run-in Results of a Multicenter, Single-arm, Phase II Trial

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