Neoadjuvant chemo-immunotherapy for lung cancer: how much is too much?
Ontology highlight
ABSTRACT:
SUBMITTER: Deboever N
PROVIDER: S-EPMC9830259 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Neoadjuvant chemo-immunotherapy for lung cancer: how much is too much?
Deboever Nathaniel N Zhang Jianjun J
Translational lung cancer research 20221201 12
Similar Datasets
Project description:Non-small cell lung cancer accounts for approximately 80-85% of all lung cancers and at present represents the main cause of cancer death among both men and women. To date, surgery represents the cornerstone; nevertheless, around 40% of completely resected patients develop disease recurrence. Therefore, combining neoadjuvant chemo-immunotherapy and surgery might lead to improved survival. Immunotherapy is normally well tolerated, although significant adverse reactions have been reported in certain patients treated with inhibitors of immune checkpoints. In this review, we explore the current literature on the use of neoadjuvant chemo-immunotherapy followed by surgery for treatment of locally advanced non-small-cell lung cancer, with particular attention to the histological aspects, ongoing trials, and the most common surgical approaches. In conclusion, neoadjuvant immunotherapy whether combined or not with chemotherapy reveals a promising survival benefit for patients with advanced non-small-cell lung cancer; nevertheless, more data remain necessary to identify the best candidates for neoadjuvant regimens.
| S-EPMC9099888 | biostudies-literature
Project description:ImportanceRandomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data.ObjectiveTo assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors.Data sourcesFull-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023.Study selectionPhase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included.Data extraction and synthesisData extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.Main outcomes and measuresTwo-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated.ResultsEight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005).Conclusions and relevanceIn this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.
| S-EPMC11022115 | biostudies-literature
Project description:PurposeImmune checkpoint inhibitors (ICIs) have been successfully used in many clinical trials related to immunotherapy. This study aimed to investigate the clinical efficacy of ICIs and prognostic factors in patients with resectable non-small cell lung cancer (NSCLC) following neoadjuvant therapy in the real world.MethodsA total of 170 consecutive patients were finally selected and divided into two groups: the preoperative chemotherapy group (n = 91) and the chemo-immunotherapy group (n = 79). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, pathological nodal disease, and ability of multivariate Cox regression analysis to predict survival. Survival was estimated using Kaplan-Meier method and compared using log-rank test.ResultsThere was a statistically significant difference in DFS between the two groups (log-rank test, P = 0.019). Multivariate Cox regression analysis showed that maximum tumor diameter (P = 0.016), higher lymph node stage (ypN1, P = 0.016; ypN2, P <0.001), and major pathological response not achieved (non-major pathological response [MPR], P = 0.011) were independent prognostic factors for worse DFS.ConclusionNeoadjuvant chemo-immunotherapy yields better effects in pathological and clinical response than chemotherapy alone, which is also associated with longer DFS in the treatment of locally advanced NSCLC. Moreover, a larger tumor specimen diameter, higher ypN staging, and non-MPR after neoadjuvant therapy were associated with worse prognosis.
| S-EPMC9081467 | biostudies-literature
Project description:IntroductionNon-small cell lung cancer (NSCLC) is the leading cause of cancer incidence and mortality worldwide. Neoadjuvant chemo-immunotherapy has led to clinical benefits in resectable NSCLC in comparison to chemo-therapy alone. Major pathological response (MPR) and pathological complete response (pCR) have been used as surrogates of neoadjuvant therapy response and clinical outcomes. However, the factors affecting the pathological response are still controversial. Therefore, in this study we retrospectively examined MPR and pCR in two different cohorts of NSCLC patients, 14 treated by chemotherapy and 12 by chemo-immunotherapy in the neoadjuvant setting.MethodsIn resected tumor specimens, different histological characteristics were evaluated: necrosis, fibrosis, inflammation, presence of organizing pneumonia, granuloma, cholesterol cleft, and reactive epithelial alterations. In addition, we evaluated how MPR impacts on event-free survival (EFS) and overall survival (OS). In a small group of patients treated by chemo-immunotherapy, a gene expression analysis of the Hippo pathway was performed both in preoperative biopsies and matched post-surgical specimens.ResultsWe observed a better pathological response in the chemo-immunotherapy treated cohort: 6/12 patients (50.0%) achieved a MPR ≤10% and 1/12 (8.3%) achieved pCR both on primary tumor and on lymph nodes. On the contrary, no patient treated with chemotherapy alone achieved pCR or MPR ≤10%. A higher amount of stroma in the neoplastic bed was observed in patients treated with immuno-chemotherapy. Moreover, patients achieving better MPR (including pCR) had significantly improved overall survival (OS) and event-free survival (EFS). After neoadjuvant chemo-immunotherapy, residual tumors showed a remarkable upregulation of genes consistent with the activation of YAP/TAZ. Also, alternative checkpoint, such as CTLA-4, were enhanced.DiscussionOur findings showed that neoadjuvant chemo-immunotherapy treatment improves MPR and pCR thus resulting in better EFS and OS. Moreover, a combined treatment could induce different morphological and molecular changes in comparison to chemotherapy alone, thus giving new insights in the assessment of pathological response.
| S-EPMC9947557 | biostudies-literature
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: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.
| S-EPMC8263648 | biostudies-literature
Project description: Not available
| S-EPMC11320276 | biostudies-literature
Project description:BackgroundFor non-small cell lung cancer (NSCLC) invading lobar bronchial orifice, sleeve lobectomy is the preferred surgical option. Neoadjuvant chemo-immunotherapy may allow R0 resection with lobectomy. This study aims to compare the long-term outcome of sleeve lobectomy and lobectomy after neoadjuvant chemo-immunotherapy.MethodsWe retrospectively screened patients undergoing neoadjuvant chemo-immunotherapy followed by lobectomy or sleeve lobectomy for NSCLC invading lobar bronchial orifice from March 2019 and April 2022. Event-free survival (EFS) was compared between sleeve lobectomy and lobectomy groups in the original cohort and the inverse probability of treatment weighting (IPTW) adjusted cohort. Cox regression was conducted for the potential association between surgical type and EFS.ResultsWe initially enrolled 248 patients. According to the inclusion criteria, the final analysis included 68 (27.4%) patients: 38 undergoing lobectomy and 30 undergoing sleeve lobectomy. The 2-year EFS was 83.3% versus 60.5% in sleeve and lobotomy groups, respectively [hazard ratio (HR) =0.46, 95% confidence interval (CI): 0.210-1.005; P=0.057]. In Cox regression analysis, improved EFS was associated with pathological complete response (pCR) (HR =0.31, 95% CI: 0.11-0.90; P=0.03) but not surgical types (HR =0.54, 95% CI: 0.22-1.5; P=0.20). In the subgroup analysis including pCR patients (n=31), median EFS was not reached (NR) in either group (P=0.8) before and after IPTW. In the non-pCR subgroup (n=37), median EFS was 21 months (95% CI: 13-NR) in lobectomy group versus not achieved (95% CI: 25-NR) in sleeve lobectomy group (P=0.04) after IPTW.ConclusionsLobectomy could be feasible for pCR patients and there is survival advantage with sleeve lobectomy in patients failing to achieve pCR after neoadjuvant chemo-immunotherapy.
| S-EPMC11921267 | biostudies-literature
Project description: Not available
| S-EPMC7225132 | biostudies-literature
Project description: Not available
| S-EPMC7815365 | biostudies-literature