First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

Ortega-Franco, Ana; Ackermann, Christoph; Paz‐Ares, Luis; Califano, Raffaele

doi:10.1016/j.esmoop.2020.100003

Cited by 25 publications

(28 citation statements)

References 59 publications

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“…Over the past 30 years, platinum-containing chemotherapy has been the standard treatment 14 . We conducted this meta-analysis with the continuous development of immunotherapy drugs and the publication and the update of more and more relative clinical trial results 15,16 . Compared with previous studies 17,18 , we have updated the data from the latest clinical trials, and our conclusions on safety are different from those of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immuno-based Therapy Versus Standard of Care in Extensive-stage Small-Cell Lung Cancer: An Updated Meta-analysis of Randomized Clinical Trials

Liu

Ying

Zhou

et al. 2022

Preprint

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Introduction Several clinical studies have shown the emergence of immune checkpoint inhibitors (ICIs) could break the standard of care and generate clinical benefits for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). We aim to assess the efficacy and safety of immuno-based therapy in patients with ES-SCLC. Methods Our search was performed in PubMed, Embase, Cochrane, and Web of Science databases for clinical studies published in English between Jan 1, 2000, and Nov 30, 2021. We extracted hazard ratios (HRs) and 95% confidence intervals (CI) of overall survival (OS) and progression-free survival (PFS), objective response rate (ORR), grade 3 or higher treatment-related adverse events (AEs), and we calculated the 95% CI together with the incidence. In addition, subgroup analysis was performed for patients with brain metastasis, smoking, and liver metastasis. Results We identified 200 records, of which 6 studies (2,905 patients) were included. The combined results showed that immuno-based therapy significantly prolonged OS (HR,0.78; 95%CI, 0.71 to 0.86; p < 0.00001), PFS (HR, 0.81,95%CI, 0.75 to 0.87; p < 0.00001) and ORR (HR, 1.06; 95%CI, 1.00 to 1.11; p = 0.03). Serious AEs (≥ 3 grade) were more frequent with immuno-based therapy [Risk Ratio (RR), 1.08; 95%CI, 1.02 to 1.14; p = 0.007]. Besides, the most common serious AEs were neutropenia (25.1%; 95%CI, 18.9% to 32.6%), anemia (12.2%; 95%CI,9.6% to 15.4%) and thrombocytopenia (8.3%; 95%CI 5.7% to 11.9%). Compared with standard of care, no obvious immuno-based therapy benefit was found for ES-SCLC patients with brain metastases at diagnosis (HR, 1.14; 0.87 to 1.46; p = 0.32) and smoking (HR, 0.88, 95%CI, 0.73 to 1.06; p = 0.19). Conclusion Our study reveals that immuno-based therapy better improves the OS and PFS than standard chemotherapy in ES-SCLC patients. Hence, our results provide new insights into the efficacy and safety of ICIs combination strategies for guiding clinical practice.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immuno-based Therapy Versus Standard of Care in Extensive-stage Small-Cell Lung Cancer: An Updated Meta-analysis of Randomized Clinical Trials

Liu

Ying

Zhou

et al. 2022

Preprint

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“…Furthermore, IMpower 133 included 10% of patients receiving PCI in both arms, whereas in CASPIAN, only the control arm was permitted to receive optional PCI, with no difference noted in the incidence of brain metastases. However, patients with asymptomatic treated brain metastases performed poorly in all arms of both studies, yet the number of patients with asymptomatic treated brain metastases was small, and no patient with untreated brain metastases was allowed, rendering the question of management of patients with brain metastases an unmet need, and a significant limitation of the two studies [66]. Three other clinical controversies not tackled in IMpower 133, and CASPIAN include the absence of consolidative thoracic radiotherapy, the exclusion of patients with disease-related borderline and/or poor performance status, as well as patients with disease-related paraneoplastic auto-immune disorders.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy in Extensive-Stage Small Cell Lung Cancer

Sayed

Blais

2021

Current Oncology

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Small cell lung cancer (SCLC) remains a poorly understood disease with aggressive features, high relapse rates, and significant morbidity as well as mortality, yet persistently limited treatment options. For three decades, the treatment algorithm of SCLC has been stagnant despite multiple attempts to find alternative therapeutic options that could improve responses and increase survival rates. On the other hand, immunotherapy has been a thriving concept that revolutionized treatment options in multiple malignancies, rendering previously untreatable diseases potentially curable. In extensive stage SCLC, immunotherapy significantly altered the course of disease and is now part of the treatment algorithm in the first-line setting. Nevertheless, the important questions that arise are how best to implement immunotherapy, who would benefit the most, and finally, how to enhance responses.

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“…The phase III CASPIAN study revealed that the combination of durvalumab significantly improved overall response rate (ORR) and prolonged OS in extensive-stage SCLC, whereas PFS could not benefit from it (5.1 versus 5.4 months) (25). Updated findings presented at the 2020 ESMO annual meeting (26) showed that patients with SCLC treated with durvalumab had a similar proportion (8.3% versus 9.5%) developed brain metastases compared to those without it.…”

Section: Discussionmentioning

confidence: 99%

Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report

et al. 2021

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BackgroundPrimary small cell neuroendocrine carcinoma (SCNEC) in the ureter is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes have not yet been thoroughly understood. Here we present a patient with advanced SCNEC in the ureter who was treated by multimodal strategies. To the best of our knowledge, this is the first literature report about the clinical outcomes of the combination of programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) and radiotherapy in patient with primary ureteral SCNEC.Case PresentationA 71-year old male presented with right flank pain and gross hematuria. A laparoscopic right nephroureterectomy was performed. He was diagnosed with primary ureteral SCNEC, pT3N0M0. Following the surgery, 4 cycles of adjuvant chemotherapy with carboplatin and etoposide (CE) were administered, with disease-free survival (DFS) of 10.1 months. He was then offered 4 cycles of palliative first-line chemotherapy with nedaplatin and irinotecan. The disease was continuously progressed, with progression-free survival (PFS) of 3.7 months. The patient subsequently received second-line treatment with PD-L1 ICI combined with radiotherapy. Unfortunately, hyperprogressive disease was found at the end of treatment. MRI and CT scan showed bilateral pubic bones, right acetabulum, and liver metastases. Without further intervention, the patient died from extensive metastatic disease 2 months after diagnosis, with overall survival (OS) of 18.2 months.ConclusionPhysicians must be aware of this rare and aggressive carcinoma at its initial presentation. Special attention should be paid to the potential likelihood of hyperprogression during the treatment.

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First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

Cited by 25 publications

References 59 publications

Efficacy and Safety of Immuno-based Therapy Versus Standard of Care in Extensive-stage Small-Cell Lung Cancer: An Updated Meta-analysis of Randomized Clinical Trials

Efficacy and Safety of Immuno-based Therapy Versus Standard of Care in Extensive-stage Small-Cell Lung Cancer: An Updated Meta-analysis of Randomized Clinical Trials

Immunotherapy in Extensive-Stage Small Cell Lung Cancer

Hyperprogression After Immunotherapy for Primary Small Cell Neuroendocrine Carcinoma of the Ureter: A Case Report

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