Neoadjuvant immunotherapy in resectable non-small cell lung cancer at a checkpoint.
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ABSTRACT:
SUBMITTER: Faltermeier CM
PROVIDER: S-EPMC8743523 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.
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Project description:The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT. Significant interest in neoadjuvant chemoimmunotherapy resulted in the conduct of multiple successful phase II trials including the Columbia trial, NADIM, SAKK 16/14, and NADIM II. Across these trials, neoadjuvant chemoimmunotherapy led to high rates of pathologic response and improved surgical outcomes without compromising surgical timing or feasibility. CheckMate-816, which was a randomized phase III trial studying neoadjuvant nivolumab in addition to chemotherapy, definitively established a benefit for neoadjuvant chemoimmunotherapy compared to chemotherapy alone for resectable NSCLC. Despite the growing literature and success of these trials, several outstanding questions remain, including the relationship between pathologic response and patient survival, the role of biomarkers such as programmed death ligand 1 and circulating tumor DNA in determining patient selection and treatment course, and the utility of additional adjuvant therapies. Longer follow-up of CheckMate-816 and other ongoing phase III trials may help address these questions. Ultimately, the complexity of managing resectable NSCLC highlights the importance of a multidisciplinary approach to patient care.
| S-EPMC10052589 | biostudies-literature
Project description:The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/- radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC.
| S-EPMC9963056 | biostudies-literature
Project description:Surgery is the standard of care for patients with operable non-small cell lung cancer (NSCLC). However, as a single modality, surgery for early stage or locally advanced NSCLC remains associated with high rates of local and distant recurrence. The addition of neoadjuvant or adjuvant chemotherapy has modestly improved outcomes. While systemic therapy paired with surgery for other malignancies such as breast cancer have resulted in far better outcomes for equivalent stage designations, outcome improvements for operable NSCLC have lagged in part as a result of trials where adjuvant chemotherapy seemed to incur harm for stage IA patients and only modest survival benefit for stage IB-IIIA patients (AJCC 7th ed.). In recent years, immunotherapy for NSCLC has emerged as a systemic therapy with significant benefit over traditional chemotherapy regimens. These advances with immune checkpoint inhibitors (ICIs) have opened the door to administering peri-operative immunotherapy for operable NSCLC. As a result, a great multitude of studies investigating the use of immunotherapy in combination with surgery for NSCLC as well as several other malignancies have emerged. In this review, we outline the rationale for neoadjuvant immunotherapy in the treatment of operable NSCLC and summarize the available evidence that include preoperative ICI as a single modality or in combination with systemic agents and/or radiotherapy. Further, we summarize how such treatment trajectories open multiple unique windows of opportunity for scientific discovery and potential therapeutic gains for these vulnerable patients.
| S-EPMC7867741 | biostudies-literature
Project description:BackgroundThe neoadjuvant use of immune checkpoint inhibitors (ICIs) in resectable non-small-cell lung cancer (NSCLC) is currently an area of active ongoing research. The place of neoadjuvant ICIs in the treatment guidelines needs to be determined. We carried out a systematic review of published data on neoadjuvant ICIs in resectable NSCLC to study its efficacy and safety.Patients and methodsA literature search was carried out using the MEDLINE (PubMed) and Embase databases to retrieve articles and conference abstracts of clinical trials measuring the efficacy [major pathological response (MPR) and pathological complete response (pCR)] and safety (failure to undergo resection, surgical delay, treatment-related adverse events (trAEs) grade ≥3) of neoadjuvant immunotherapy in resectable NSCLC until July 2021.ResultsNineteen studies with a total of 1066 patients were included in this systematic review. Neoadjuvant immunotherapy was associated with improved pathological response rates, especially in combination with chemotherapy. Using mono ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI, the MPR rates were 0%-45%, 50%, 73%, 53%, and 27%-86%, respectively. Regarding pCR, the rates were 7%-16%, 33%-38%, 27%, 27%, and 9%-63%, respectively. Safety endpoints using monotherapy-ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI showed a failure to undergo resection in 0%-17%, 19%-33%, 8%, 13%, and 0%-46%, respectively. The trAEs grade ≥3 rates were 0%-20%, 10%-33%, 7%, 23%, and 0%-67%, respectively.ConclusionIn patients with resectable NSCLC stage, neoadjuvant immunotherapy can improve pathological response rates with acceptable toxicity. Further research is needed to identify patients who may benefit most from this approach, and adequately powered trials to establish clinically meaningful benefits are awaited.
| S-EPMC8414043 | biostudies-literature
Project description:PurposeImmunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival.MethodsA systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible.ResultsEighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency.ConclusionThe present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.
| S-EPMC8628782 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) are highly concerned in the treatment of non-small cell lung cancer (NSCLC), represented by inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), and inhibitors of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The introduction of immunotherapy in the treatment of perioperative NSCLC has improved the prognosis to a great extent, as demonstrated by several phase II and III clinical trials. The target population for immunotherapy in early-stage NSCLC is still under discussion, and the biomarkers for neoadjuvant immunotherapy population selection are the next pending problem. The predictive efficacy of many potential makers is still being explored, including PD-L1 expression levels, tumor mutation burden, circulating tumor DNA, components of the tumor microenvironment, and several clinical factors. We summarize key findings on the utility of ICIs in clinical trials of preoperative NSCLC patients and conclude analyses of relevant biomarkers to provide a better understanding of potentially predictive biomarkers in neoadjuvant immunotherapy.
| S-EPMC9902866 | biostudies-literature
Project description:ObjectivesRecent clinical studies have demonstrated that immunotherapy-based neoadjuvant therapy have promising effectiveness for patients with resectable non-small cell lung cancer (NSCLC) in terms of pathologic response. Therefore, we performed this study to investigate whether immunotherapy-based neoadjuvant therapy is effective and safe for patients with resectable NSCLC.Materials and methodsThis open-label observational two-arm clinical study was performed at Shanghai Chest Hospital in China with patients who had resectable NSCLC and received two to three cycles of immunotherapy-based neoadjuvant therapy or neoadjuvant chemotherapy alone, followed by surgical resection. The primary endpoint was a major pathologic response (MPR). The secondary endpoints include a complete pathological response (pCR), a radiologic response to neoadjuvant therapy (TRR), event-free survival (EFS), and overall survival (OS).ResultsA total of 51 patients was included in this clinical study, of which 31 patients received immunotherapy-based neoadjuvant therapy and 20 patients received neoadjuvant chemotherapy alone. The percentage of patients achieving a major pathologic response was 41.9% with immunotherapy-based neoadjuvant therapy and 15.0% (95% CI, 0.008 to 0.468; P = 0.043) with neoadjuvant chemotherapy alone. The percentage of patients with pathologic complete response was 19.4% in the immunotherapy-based group and 5% (95% CI, -0.069 to 0.318; P = 0.223) in the chemotherapy group. The radiographic response rate was 71% after immunotherapy-based neoadjuvant therapy and 60% (95% CI, -0.143 to 0.359; P = 0.417) after neoadjuvant chemotherapy. At a median follow-up of 28 months, the median EFS and OS endpoints were not reached.ConclusionsNeoadjuvant immunotherapy offers a considerable advantage over chemotherapy alone for resectable NSCLC in terms of the major pathologic response. Moreover, it did not enhance the risk of adverse events or hinder surgical resection.
| S-EPMC10560710 | biostudies-literature
Project description:Surgical resection is the mainstay of therapy for patients with resectable and operable early stage non-small cell lung cancer (NSCLC). Surgery alone yields an unacceptably high rate of lung cancer recurrence. The addition of chemotherapy to surgery as adjuvant or neoadjuvant treatment can improve survival rates by roughly 5% at 5 years. Recently, major advances in cancer immunotherapy have led to better outcomes for many patients with lung cancer. Monoclonal antibodies to programmed death 1 and its ligand are now approved for both first and second line treatment patients with metastatic lung cancer. In this review, we will outline the rationale and current research strategies investigating the role of immunotherapy in resectable NSCLC.
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Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.
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