Neoadjuvant therapy in localized non-small cell lung cancer: can we do better than chemotherapy?
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ABSTRACT:
SUBMITTER: Chau B
PROVIDER: S-EPMC8798936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations) is a major challenge.
| S-EPMC4940012 | biostudies-literature
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| S-EPMC10413032 | biostudies-literature
Project description:BackgroundLarge scale sequencing efforts defined common molecular alterations in non-small cell lung cancer (NSCLC) and revealed potentially druggable mutations. Yet, systematic data on the changes of the respective molecular profiles under standard therapy in NSCLC are limited.Results14 out of 68 observed coding mutations (21%) and 6 out of 33 (18%) copy number variations (CNV) were lost or gained during therapy. Mutational and CNV changes clustered in 6/37 (16%) and 3/37 (8%) patients. Changes in clinically relevant mutations were rare but present in single cases for genes such as BRAF and PIK3CA. The type of radiochemotherapy but not the duration of therapy impacted on the frequency of mutational changes.MethodsWe established a lung cancer specific next-generation sequencing panel covering ~7500 hotspots of 41 genes frequently mutated in NSCLC and performed ultradeep multigene sequencing of 37 corresponding pre- and post-therapeutic formalin fixed paraffin-embedded specimens to discover mutational changes and copy number variations under neo-adjuvant radio- (RTX) and/or chemotherapy (CTX).ConclusionWe unraveled changes in common driver gene candidates in NSCLC under neo-adjuvant therapy. Our data shed first light on the genetic changes of NSCLC under conventional therapy and might be taken into account when the relevance of sequential biopsy approaches is discussed.
| S-EPMC5045431 | biostudies-literature
Project description:BackgroundNeoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC.MethodsThis was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed.ResultsOf the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS <50% and ≥50% (all P > 0.05).ConclusionNeoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.
| S-EPMC10559199 | biostudies-literature
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| S-EPMC9096278 | biostudies-literature
Project description:IntroductionSurvival rates for early-stage non-small cell lung cancer (NSCLC) remain poor despite the decade-long established standard of surgical resection and systemic adjuvant therapy. Realizing this, researchers are exploring novel therapeutic targets and deploying neoadjuvant therapies to predict and improve clinical and pathological outcomes in lung cancer patients. Neoadjuvant therapy is also increasingly being used to downstage disease to allow for resection with a curative intent. In this review, we aim to summarize the current and developing landscape of using neoadjuvant therapy in the management of NSCLC.MethodsThe PubMed.gov and the ClinicalTrials.gov databases were searched on 15 January 2023, to identify published research studies and trials relevant to this review. One hundred and seven published articles and seventeen ongoing clinical trials were selected, and relevant findings and information was reviewed.Results & discussionNeoadjuvant therapy, proven through clinical trials and meta-analyses, exhibits safety and efficacy comparable to or sometimes surpassing adjuvant therapy. By attacking micro-metastases early and reducing tumor burden, it allows for effective downstaging of disease, allowing for curative surgical resection attempts. Research into neoadjuvant therapy has necessitated the development of surrogate endpoints such as major pathologic response (MPR) and pathologic complete response (pCR) allowing for shorter duration clinical trials. Novel chemotherapy, immunotherapy, and targeted therapy agents are being tested at a furious rate, paving the way for a future of personalized systemic therapy in NSCLC. However, challenges remain that prevent further mainstream adoption of preoperative (Neoadjuvant) therapy. These include the risk of delaying curative surgical resection in scenarios of adverse events or treatment resistance. Also, the predictive value of surrogate markers of disease cure still needs robust verification. Finally, the body of published data is still limited compared to adjuvant therapy. Addressing these concerns with more large scale randomized controlled trials is needed.
| S-EPMC10739417 | biostudies-literature
Project description: Not available
| S-EPMC11002516 | biostudies-literature
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.
| S-EPMC9215714 | biostudies-literature
Project description:Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy into treatment plans in both the neoadjuvant and consolidation settings. Currently available data of anti-PD-(L)1 therapies in stage III NSCLC are limited. However, interim results from two studies are encouraging: a phase II neoadjuvant nivolumab trial demonstrated early signals of efficacy, and the phase III PACIFIC trial of durvalumab recently showed significant improvement in progression-free survival (PFS). Preliminary results for the phase II DETERRED trial of durvalumab have also been reported. Many studies are testing anti-PD-(L)1 therapies in the neoadjuvant and consolidation settings for stage III NSCLC, and will be discussed. As these studies mature they may provide further treatment options in management of stage III NSCLC.
| S-EPMC5861269 | biostudies-literature
Project description:Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non-small cell lung cancer (NSCLC) patients.Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28-dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated tumor-infiltrating lymphocytes than those observed in PBMCs. Surprisingly, we found 4 cases of preexisting tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating regulatory T cells and MDSCs.Conclusions: This study did not meet the primary endpoint of detecting an increase in blood-based TAA T-cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early-stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunologic data from combined immune checkpoint blockade immunotherapies. Clin Cancer Res; 23(24); 7474-82. ©2017 AACR.
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