The role of immunotherapy in small cell lung cancer

Calles, Antonio; Aguado, Gema; Sandoval, Carmen; Álvarez, Rosa

doi:10.1007/s12094-018-02011-9

Cited by 85 publications

(78 citation statements)

References 86 publications

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“…The majority of SCLC is extensive-stage at the time of diagnosis, with median overall survival 8-13 months. 56 Standard first-line therapy includes combination platinum and etoposide chemotherapy. Supporting the use of immune therapies in SCLC is their high immunogenicity, with an increased prevalence of associated paraneoplastic disorders.…”

Section: Immunotherapy In the Era Of Precision Medicinementioning

confidence: 99%

Precision Medicine in Lung Cancer

Lam¹

2020

EMJ Oncol

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Lung cancer has a devastating global impact, with diagnosis of more than 2 million new cases annually, and poor long-term survival. Recently, the landscape of lung cancer diagnosis, staging, and treatment has changed profoundly, with further developments on the horizon. In this review, lung cancer histological subtypes are discussed, with a focus on non-small cell lung cancer, along with current and evolving approaches to diagnosis and staging. Therapeutic options in the era of precision medicine will also be considered within the context of targetable oncogenic driver mutations and the growing field of immuno-oncology.

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Section: Immunotherapy In the Era Of Precision Medicinementioning

confidence: 99%

Precision Medicine in Lung Cancer

Lam¹

2020

EMJ Oncol

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“…Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers [2] with 6.0 cases per 100,000 individuals in 2014 [3]. SCLC is strongly associated with exposure to tobacco and grows rapidly, with early widespread metastases and frequent brain involvement [4, 5]. This disease subtype is also associated with high mutation rates, including rare oncogenic drivers and inactivation of the TP53 and RB1 tumor suppressor genes [6].…”

Section: Introductionmentioning

confidence: 99%

“…This disease subtype is also associated with high mutation rates, including rare oncogenic drivers and inactivation of the TP53 and RB1 tumor suppressor genes [6]. Approximately 30% of patients with SCLC present with limited‐stage disease (LS‐SCLC), with the remaining 70% diagnosed with extensive‐stage SCLC (ES‐SCLC) where the tumor extends beyond one hemithorax or cannot be encompassed within standard radiation fields [4, 7, 8]. Overall prognosis for patients with ES‐SCLC is poor [8–11].…”

Section: Introductionmentioning

confidence: 99%

“…ES‐SCLC is highly responsive to chemotherapy [4, 12], and standard first‐line treatment is a platinum plus etoposide doublet [4]. This treatment often achieves rapid responses with good overall response rates (ORRs, up to 75%) although these are often transient with a median progression‐free survival (PFS) of only 5.5 months and a median overall survival (OS) of less than 10 months [4, 8–10]. Second‐line options include the topoisomerase inhibitor topotecan or rechallenging with carboplatin‐etoposide.…”

Section: Introductionmentioning

confidence: 99%

“…Given the rapid progression of SCLC, third‐line therapy is rare [20]. Options for SCLC have changed little in the last few decades [4, 21], underscoring the urgent need for new therapies.…”

Section: Introductionmentioning

confidence: 99%

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Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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Background Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive‐stage SCLC (ES‐SCLC). Although ES‐SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES‐SCLC based on phase III evidence. Methods Published and presented literature on phase III data addressing use of ICIs in ES‐SCLC was identified using the key search terms “small cell lung cancer” AND “checkpoint inhibitors” (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first‐line, one evaluating ICIs as first‐line therapy maintenance, and one assessing ICI monotherapy after progression on platinum‐based chemotherapy. The addition of ipilimumab or tremelimumab to first‐line treatment or as first‐line maintenance did not improve survival. Two out of three studies combining PD‐1/PD‐L1 inhibitors with first‐line platinum‐based chemotherapy demonstrated significant long‐lasting survival benefits and improved quality of life with no unexpected safety concerns. PD‐1/PD‐L1 inhibitors as first‐line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited‐stage SCLC. Conclusion The addition of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy for ES‐SCLC prolongs survival and improves quality of life. Implications for Practice Platinum‐based chemotherapy has been standard of care for extensive‐stage small cell lung cancer (ES‐SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first‐line, as first‐line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first‐line ES‐SCLC. Biomarker research and investigations into the role of ICIs for limited‐stage disease are ongoing.

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Conserved immuno‐collagenic subtypes predict response to immune checkpoint blockade

Mei,

Cai,

et al. 2024

Cancer Communications

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BackgroundImmune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy.MethodsWe analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno‐collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in‐house samples. Additionally, novel therapeutic targets were identified based on these established immuno‐collagenic subtypes.ResultsOur categorization divided tumors into three subtypes: “soft & hot” (low collagen activity and high immune infiltration), “armored & cold” (high collagen activity and low immune infiltration), and “quiescent” (low collagen activity and immune infiltration). Notably, “soft & hot” tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7‐H3), an available drug target, as strongly expressed in “armored & cold” tumors, relating with poor prognosis.ConclusionThis study introduces histopathology‐based universal immuno‐collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

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The role of immunotherapy in small cell lung cancer

Cited by 85 publications

References 86 publications

Precision Medicine in Lung Cancer

Precision Medicine in Lung Cancer

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Conserved immuno‐collagenic subtypes predict response to immune checkpoint blockade

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