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Immunotherapy in small cell lung cancer: one step at a time: a narrative review.

ABSTRACT: Chemotherapy with or without radiotherapy has been the standard of care for many years for patients with small cell lung cancer (SCLC). Despite exceptionally high responses (up to 80%) with chemotherapy, the majority of patients relapse rapidly within weeks to months after treatment completion. Therefore, new and better treatment options are necessary. Recently, synergistic activity has been reported for the addition of immune checkpoint inhibitors (ICI) to standard platinum-based chemotherapy in the therapeutic strategy of advanced SCLC. For the first time after several decades, a significant survival improvement was achieved for this population. However, the overwhelming majority of patients do not respond to ICI, or relapse rapidly. There is need for better knowledge about the biology, histopathologic features, and molecular pathways of SCLC. This can probably help to identify the optimal predictive biomarkers, which are warranted to develop an individual therapeutic strategy including the rational use of a combination of immunotherapeutic agents. Here, we provide an overview of the rationale for and clinical results of the completed and ongoing trials using different strategies of immunotherapy in SCLC. In addition, opportunities for further improvement of therapies will be discussed, including the addition of radiotherapy, co-stimulatory antibodies, and other immune modifying agents.

SUBMITTER: Dumoulin DW

PROVIDER: S-EPMC8264327 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Immunotherapy in small cell lung cancer: one step at a time: a narrative review.

Dumoulin Daphne W DW Dingemans Anne-Marie C AC Aerts Joachim G J V JGJV Remon Jordi J De Ruysscher Dirk K M DKM Hendriks Lizza E L LEL

Translational lung cancer research 20210601 6

Chemotherapy with or without radiotherapy has been the standard of care for many years for patients with small cell lung cancer (SCLC). Despite exceptionally high responses (up to 80%) with chemotherapy, the majority of patients relapse rapidly within weeks to months after treatment completion. Therefore, new and better treatment options are necessary. Recently, synergistic activity has been reported for the addition of immune checkpoint inhibitors (ICI) to standard platinum-based chemotherapy i ...[more]

PMID: 34295691

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Project description:Background and objectiveRole of radiotherapy (RT) in the era of immuno-oncology (IO) in advanced non-small cell lung cancer (NSCLC) is rapidly changing. RT is not only intended for addressing palliation symptoms but also is considered as a potential tool potentializing an immunogenic effect of given drugs. However, the best timing, techniques, doses, volumes, and its use for asymptomatic patients is a subject of research. We performed a review on the role of palliative RT schedules in combination with IO for advanced NSCLC. Indications in symptomatic and asymptomatic patients, outcomes, toxicity, and possible developments are discussed.MethodsA literature search was conducted in MEDLINE and PubMed databases and clinicaltrials.gov using the keywords 'lung cancer' AND "immunotherapy" AND 'radiotherapy' OR "palliative radiotherapy".Key content and findingsBody of evidence indicate that palliative RT used in combination with IO is effective in terms of symptom management and safe; does not increase the risk of serious side effects, including serious pulmonary toxicity. We have limited data evidencing improvement of survival by addition of short ablative RT dose to one site of the disease to IO in oligometastatic NSCLC. Some data indicate that short ablative doses of stereotactic body radiation therapy (SBRT) are more effective with regard to treatment response and survival than protracted RT schedule with lower fractional doses. However, this may be a selection bias of better prognostic patients who underwent SBRT. The use of steroids being a potential concern during IO should not be prohibited if clinically indicated during palliative RT. Its detrimental effect shown in some studies may also be a result of selection bias, because steroids given for not cancer-related causes during IO did not decrease survival.ConclusionsRT for symptom management may be used during, directly before or after IO. This has a potential to ease symptom burdens and improve performance status (PS). However, still more studies are needed to establish optimal guidelines in asymptomatic patients for appropriate timing, volumes, dose, and fractionation schedules of palliative RT use in combination with IO.

Project description:Background and objectiveImmune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.MethodsRelevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms "non-small-cell lung cancer", "NSCLC", "neoadjuvant", "immunotherapy", "immune checkpoint inhibitors", "mechanisms", and "toxicity". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.Key content and findingsAfter reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.ConclusionsNeoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.

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Immunotherapy in small cell lung cancer: one step at a time: a narrative review.

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Immunotherapy in small cell lung cancer: one step at a time: a narrative review.

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