Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial

Zhou, Caicun; Huang, Dingzhi; Fan, Yun; Yu, Xinmin; Liu, Yunpeng; Shu, Yongqian; Ma, Zhiyong; Wang, Ziping; Cheng, Ying; Wang, Jie; Hu, Sheng; Liu, Zhihua; Poddubskaya, Elena; Dişel, Umut; Akopov, Andrey; Dvorkin, Mikhail; Zheng, Wei‐Shi; Ma, Yang; Wang, Yan; Li, Songzi; Yu, Cunjing; Rivalland, Gareth

doi:10.1016/j.jtho.2022.09.217

Cited by 40 publications

(35 citation statements)

References 26 publications

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“…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%

“…Study methodological quality was assessed by using Jadad ranking system, that evaluates quality of randomization, CheckMate 017 [9] >1 Squamous NSCLC PD-1 Nivolumab (135) Chem (137) 208 64 >11 CheckMate 026 [10] 1 NSCLC PD-1 Nivolumab + chem (271) Chem (270) 332 209 13.5 CheckMate 057 [11] >1 Nonsquamous NSCLC PD-1 Nivolumab (292) Chem (290) 319 263 >13.2 TASUKI-52 [12] 1 Nonsquamous NSCLC PD-1 Nivolumab + BEV + chem (273) BEV + chem (275) 411 139 13.7 KEYNOTE 010 [13] >1 NSCLC PD-1 Pembrolizumab + chem (690) Chem (343) 634 399 67.4 (60.0-77.9) KEYNOTE 024 [14] 1 NSCLC PD-1 Pembrolizumab (154) Chem (151) 187 118 25.2 KEYNOTE 042 [15] 1 NSCLC PD-1 Pembrolizumab (638) Chem (637) 902 372 12.8 (6.0-20.0) KEYNOTE 189 [16] 1 Nonsquamous NSCLC PD-1 Pembrolizumab + chem (410) Chem (206) 363 253 10.5 KEYNOTE 407 [17] 1 Squamous NSCLC PD-1 Pembrolizumab + chem (278) Chem (281) 455 104 7.8 EMPOWER-Lung 1 [18] 1 NSCLC PD-1 Cemiplimab (283) Chem (280) 479 84 10.8 (7.6-15.8) EMPOWER-Lung 3 [19] 1 NSCLC PD-1 Cemiplimab + chem (312) Chem (154) 391 75 16.3 (13.9-19.1) CameL-sq [20] 1 Squamous NSCLC PD-1 Camrelizumab + chem (193) Chem (196) 359 30 13.5 (1.1-23.6) CameL [21] 1 Nonsquamous NSCLC PD-1 Camrelizumab + chem (205) Chem (207) 295 117 11.9 (9.0-14.9). RATIONALE 303 [22] >1 NSCLC PD-1 Tislelizumab (535) Chem (270) 622 183 16.0 (0.3-43.5) RATIONALE 304 [23] 1 Nonsquamous NSCLC PD-1 Tislelizumab + chem (223) Chem (111) 247 87 9.8 (9. 23-10.38).…”

Section: Quality Assessmentmentioning

confidence: 99%

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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

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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.

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“…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%

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

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“…The PFS in the patient with squamous cell carcinoma was 10.5 months and their OS was more than 24 months. Based on CheckMate-078 (31), RATIONALE-303 (32), and OAK studies (33), these two patients had a better significant prognosis, and follow-up is still ongoing. We will continue to track the changes in depigmentation in these patients in the future, and, if appropriate, obtain histological information of the extended depigmentation to confirm the pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Immune checkpoint inhibitor-related vitiligo-like depigmentation in non-melanoma advanced cancer: A report of three cases and a pooled analysis of individual patient data

Rao

Zheng²,

Wen³

et al. 2023

Front. Oncol.

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BackgroundVitiligo-like depigmentation is a common skin adverse event in patients receiving immunotherapy for malignant melanoma, but has been rarely reported in patients with non-melanoma malignancies. To better understand this immune-related adverse event, we reviewed a series of cases of immunotherapy induced vitiligo-like depigmentation in patients with cancers other than malignant melanoma.Case presentationWe report three cases of vitiligo-like depigmentation after immune checkpoint inhibitor treatment in gastric adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma. The first case was treated with camrelizumab, the second was treated with QL1706 injection and sintilimab, and the third was treated with tislelizumab. Pembrolizumab, nivolumab, and ipilimumab caused the majority of vitiligo-like depigmentation, and all three of our patients experienced similar vitiligo-like depigmentation after taking other immune checkpoint inhibitors.MethodsThree patients who presented with vitiligo-like depigmentation after treatment with immune checkpoint inhibitors were selected. The clinical features, including radiological and histological examination, and the treatment process were reviewed. Eighteen previously published cases of vitiligo-like depigmentation were also used to analyze the results. The severity of vitiligo-like depigmentation in these cases was graded according to the Common Terminology Criteria for Adverse Events, version 5.0.ResultsVitiligo-like depigmentation occurred in 13 men (61.90%) and 8 women (38.10%), aged from 46 to 79 years, with an average age of 69.9 years. Of the 21 reviewed cases, vitiligo-like depigmentation was described in lung cancer (13/21, 61.90%), clear cell renal cell carcinoma (2/21, 9.52%), acute myeloid leukemia (1/21, 4.76%), cholangiocarcinoma (1/21, 4.76%), urothelial carcinoma (1/21, 4.76%), oral squamous cell carcinoma (1/21, 4.76%), esophageal squamous cell carcinoma (1/21, 4.76%), and gastric adenocarcinoma (1/21, 4.76%). The severity of vitiligo-like depigmentation after immunotherapy was unrelated to sex, age, cancer type, previous autoimmune diseases, and medication.ConclusionsVitiligo-like depigmentation is a non-specific skin adverse event in melanoma immunotherapy, but arises as a direct result of treatment with immune checkpoint inhibitors. Vitiligo-like depigmentation has an irregular location, is not limited to direct sunlight cracks, and has also been reported on hair on the head, eyelashes, and eyebrows. People without any skin or autoimmune diseases can also experience vitiligo-like depigmentation after immunotherapy; the incidence of which is irrespective of sex, age, cancer type, previous autoimmune diseases, and medication.

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“…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. The ALTER0303 study ( 10 ) demonstrated a median OS extension of 3.3 months for patients in the anlotinib arm compared to the placebo arm (9.6 months vs 6.3 months); and a median PFS extension of 4.0 months (5.4 months vs 1.4 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

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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.

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Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial

Cited by 40 publications

References 26 publications

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

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

Case Report: Immune checkpoint inhibitor-related vitiligo-like depigmentation in non-melanoma advanced cancer: A report of three cases and a pooled analysis of individual patient data

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

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