Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study

Xu, Jianming; Kato, Ken; Raymond, Eric; Shu, Yongqian; Pan, Yueyin; Park, Sook Ryun; Lu, Ping; Jiang, Yi; Zhang, Jingdong; Wu, Xiaohong; Yao, Yunlong; Shen, Lin; Kojima, Takashi; Gotovkin, Evgeny; Ishihara, Ryu; Wyrwicz, Lucjan; Cutsem, Éric Van; Jiménez‐Fonseca, Paula; Lin, Chen‐Yuan; Wang, Lei; Shi, Jingwen; Li, Liyun; Yoon, Harry H.

doi:10.1016/s1470-2045(23)00108-0

Cited by 101 publications

(77 citation statements)

References 24 publications

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“…[14][15][16] ORRs reported for pembrolizumab, nivolumab, or tislelizumab in combination with chemotherapy ranged from 45.0% to 63.0%, whereas median DoR ranged from 7.1 to 8.4 months, and median OS and PFS ranged from 12.4 to 17.2 months and 5.8 to 7.3 months, respectively. [14][15][16] Several reasons may explain the lower clinical response in this study compared with KEYNOTE-590, CheckMate 648, and RATIONALE-306, including the small number of patients enrolled in this study and the number of treatment cycles received. [14][15][16] Further randomized trials with larger patient populations are needed to fully assess the antitumor activity of this regimen and to compare directly with current standards of care.…”

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of first‐line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma

Lee,

Kim,

Keam

et al. 2023

Cancer Medicine

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BackgroundAdvanced or metastatic esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis; new first‐line systemic treatment options are needed. Combining immuno‐oncology therapies with standard chemotherapy may represent a promising approach for the treatment of solid tumors. Results from a Phase Ib study evaluating durvalumab with tremelimumab and chemotherapy in patients with advanced or metastatic ESCC are reported.MethodsAdults with advanced or metastatic ESCC who were candidates for first‐line platinum‐based chemotherapy received durvalumab 1500 mg (Day 1), tremelimumab 75 mg (Day 1), cisplatin 80 mg/m2 (Day 1) and 5‐fluorouracil (5‐FU) 800 mg/m2 (Days 1–5) in 28‐day cycles until disease progression or discontinuation due to toxicity. The study consisted of safety run‐in (Part A) and expansion (Part B) periods. The primary endpoint was safety. Antitumor activity was an exploratory endpoint.ResultsSixteen patients were enrolled, 6 in Part A and 10 in Part B, and received a median of 4.0 treatment cycles. All patients were Asian; median age was 65.0 years. All patients experienced adverse events (AEs) related to cisplatin and 5‐FU, and 8 (50.0%) patients experienced AEs related to durvalumab and tremelimumab. Grade ≥3 treatment‐related AEs occurred in 7 (43.8%) patients. There were no deaths associated with AEs. Six (37.5%) patients achieved an objective response. Median progression‐free survival was 3.75 months, and median overall survival was 9.69 months.ConclusionsDurvalumab with tremelimumab and chemotherapy demonstrated manageable safety and antitumor activity in patients with advanced or metastatic ESCC, warranting further investigation in randomized trials. Registered with ClinicalTrials.gov: NCT02658214.

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Section: Discussionmentioning

confidence: 99%

Safety and tolerability of first‐line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma

Lee,

Kim,

Keam

et al. 2023

Cancer Medicine

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“…When it comes to chemoimmunotherapy, it seems that anti‐PD1 plus TP could provide greater survival benefit than anti‐PD1 plus CF 2–5,23–25 . Immunogenicity of paclitaxel and fluorouracil might play an essential role.…”

Section: Heterogenicity Of Trialsmentioning

confidence: 99%

“…In second‐line randomized ESCC trails, the percentage of ≥3 grades AEs were 20% to 46% lower in ICI monotherapy arm than in chemotherapy arm (ICI vs. Chemo: 18% vs. 64% [ATTRACTION‐3], 31 5% vs. 45% [KEYNOTE‐181], 30 19% vs. 39% [ESCORT], 32 19% vs. 56% [RATIONALE‐302] 29 ). In first‐line ESCC randomized trials except ESCORT‐1, the percentage of ≥3 grades AEs were 3%–11% higher in chemoimmunotherapy arm than in chemotherapy arm (chemoimmunotherapy vs. chemotherapy: 72% vs. 68% [KEYNOTE‐590], 23 47% vs. 36% [CheckMate‐648], 24 67% vs. 65% [RATIONALE‐306], 2 73% vs. 70% [JUPITOR‐06], 4 60% vs. 55% [ORIENT‐15], 5 63% vs. 68% [ESCORT‐1] 3 ). Furthermore, TRAEs caused by chemoimmunotherapy led to treatment discontinuation in 3%–15% of ESCC patients.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…An interesting geographic pattern was observed regarding the prevalence of EAC and ESCC. Eastern Asia, especially China, exhibits the highest regional incidence rates with ESCC being the predominant histological type, and thus many trials evaluating the combination of chemotherapy and immunotherapy (chemoimmunotherapy) in ESCC were mainly conducted in China 2–6 . On the other hand, EAC contributes to approximately two‐thirds of esophageal cancer population in western countries, such as the United States, the United Kingdom, Australia, and so on.…”

Section: Introductionmentioning

confidence: 99%

“…However, results from recent landmark trials using chemoimmunotherapy have brought revolutionary changes to the existing treatment strategy for ESCC patients. These practice‐changing trials consist of KEYNOTE‐590, CheckMate‐648, RATIONALE‐306, ESCORT‐1, JUPITOR‐06, ORIENT‐15, and ASTRUM‐007 2–5,23–25 . Among these trials, the regimens might have some differences, but most of them investigate ICI or placebo plus investigator‐chosen chemotherapy (ICC; platinum and fluoropyrimidine or platinum and paclitaxel) as treatment for ESCC.…”

Section: Introductionmentioning

confidence: 99%

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Chemoimmunotherapy for esophageal squamous cell carcinoma—Summary and discussion of recent clinical trials

Zhang

Huang

et al. 2023

MedComm – Future Medicine

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As a kind of carcinoma with increasing morbidity, poor prognosis, and high mortality, esophageal squamous cell carcinoma (ESCC) is challenging for clinical management. Chemotherapy has been the standard treatment for ESCC over decades, while its clinical outcomes remain unsatisfying. And the regimen that combine standard chemotherapy with targeted therapy also demonstrates little effect. However, the advent of immune checkpoint inhibitors (ICI) proved to be a game changer in cancer treatment. Recent clinical trials had sprung up to evaluate the combined effect of ICI and chemotherapy regarding first‐line ESCC treatment. What's more, researchers attempt to explore the possibility to implement ICI monotherapy regarding second‐line ESCC treatment. In conclusion, most of the first‐line trails present inspiring achievement, while ICI monotherapy indicates little improvement for ESCC treatment. To point out the heterogenicity that could be the potential reasons biasing the pooled results, the differences of PD‐L1 immunohistochemistry (IHC) assays, geographic regions, chemotherapy regimens, and sex disparity among these trails are discussed respectively. In addition, the adverse events occurred during the trails are summarized, which confirm the safety of immunotherapy and chemoimmunotherapy. The article comprehensively reviews the representative explorations of using chemoimmunotherapy strategies in ESCC, as well as the deficiencies among them. Moreover, we highlight some feasible approaches. It will be beneficial for conducting more precise clinical trials on chemoimmunotherapy for ESCC in the future, including the use of more appropriate PD‐L1 IHC assays, careful consideration of the heterogeneity of the enrolled population and the optimal combination of chemotherapy and ICI.

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Neoadjuvant chemoimmunotherapy was associated with better short‐term survival of patients with locally advanced esophageal squamous cell carcinoma compared to neoadjuvant chemoradiotherapy

Duan,

Zhao,

Shang

et al. 2024

Cancer Medicine

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IntroductionThe chemotherapy and immunotherapy combination is currently the primary strategy to treat metastatic esophageal squamous cell carcinoma (ESCC). Neoadjuvant chemoimmunotherapy (NCIT) is being intensively investigated for treating locally advanced ESCC.ObjectiveWe compared the efficacy and safety of NCIT and neoadjuvant chemoradiotherapy (NCRT) to treat locally advanced ESCC.MethodsWe included 214 locally advanced ESCC patients who were administered neoadjuvant therapy from May 2014 to April 2022. The patients were grouped according to two neoadjuvant protocols (NCIT and NCRT) routinely used at our institution. Perioperative findings, pathological results, and survival data were compared between the two groups by conducting unmatched and 1:1 propensity score matching (PSM) analyses.ResultsFollowing 1:1 PSM analysis of the confounders, 66 patients were allocated to each of the two groups. Time span between neoadjuvant therapy completion and esophagectomy was significantly longer after NCRT than that after NCIT (47.1 ± 13.2 days vs. 34.7 ± 8.8 days; p < 0.001). The NCIT group exhibited significantly greater number of harvested lymph nodes than the NCRT group (33.6 ± 12.7 vs. 21.7 ± 10.2; p < 0.001). The pathological complete response and major pathological response rates were similar between the two groups [NCIT group: 25.8% (17/66) and 62.1% (41/66), respectively; NCRT group: 27.3% (18/66) and 56.1% (37/66), respectively (p > 0.05)]. The overall incidence of pneumonia, anastomotic leakage, or postoperative complications did not differ significantly between the two groups. The 2‐year cumulative overall survival rates and the 2‐year disease‐free survival rates of the NCIT and NCRT groups were 80.2% and 62.2%, respectively (p = 0.029) and 70.0% and 50.8%, respectively (p = 0.023).ConclusionIn locally advanced ESCC patients, short‐term survival after NCIT is superior to that after NCRT, with similar perioperative and pathological outcomes.

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Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study

Cited by 101 publications

References 24 publications

Safety and tolerability of first‐line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma

Safety and tolerability of first‐line durvalumab with tremelimumab and chemotherapy in esophageal squamous cell carcinoma

Chemoimmunotherapy for esophageal squamous cell carcinoma—Summary and discussion of recent clinical trials

Neoadjuvant chemoimmunotherapy was associated with better short‐term survival of patients with locally advanced esophageal squamous cell carcinoma compared to neoadjuvant chemoradiotherapy

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