Perioperative Immunotherapy Research Articles

Perioperative immunotherapy in soft tissue sarcomas.

Perioperative immunotherapy in soft tissue sarcomas.

Clinicopathological Characteristics and Perioperative Treatment of Epstein-Barr Virus-Associated Gastric Cancer: A Retrospective Study.

The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed and Cox regression analysis was performed to identify risk factors. The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion. EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain.

Landscape of subsequent therapies in perioperative immunotherapy trials across multiple cancer types

Landscape of subsequent therapies in perioperative immunotherapy trials across multiple cancer types

Perioperative Tislelizumab plus intensity modulated radiotherapy in resectable hepatocellular carcinoma with macrovascular invasion: a phase II trial

Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.

Tissue and Imaging Biomarkers of Response to Neoadjuvant Nivolumab or Nivolumab plus Ipilimumab in Patients with Resectable Hepatocellular Carcinoma

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC. Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis of more than 70%. Data comparing patients with MPR versus those without were summarized using descriptive statistics and compared using the Wilcoxon rank-sum test. Results: Patients with MPR after neoadjuvant immunotherapy tended to have larger tumors (mean 9.52 vs. 4.99 centimeters; p = 0.050). They had a significant reduction in tumor size posttreatment (14.67% reduction vs. 9.15% increase in size; p = 0.042) and a nonsignificant decrease in serum AFP (−24.20% vs. −14.00%; p = 0.085). Further, patients with MPR had a greater increase in intratumoral expression levels of CD8 (26.92% vs. −0.04%; p = 0.026), granzyme B (15.56% vs. −2.24%; p = 0.011), and PD-1 (20.17% vs. 0.40%; p = 0.048) but not PD-L1 (7.69% vs. 0.57%; p = 0.26). For imaging biomarkers, tumor and liver fibrosis were comparable before and after neoadjuvant therapy in patients with MPR versus nonresponders. Conclusion: Changes in tumor size, immune cell infiltration, and immune cell activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.

Perioperative immunotherapy for non-small cell lung cancer: consensus and controversy (2024 edition)

Lung cancer is the malignant tumour with the highest morbidity and mortality rate in China, among which non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80% to 85%. Radial surgery is the standard treatment for early-stage NSCLC, but postoperative recurrence is an inevitable problem in clinical practice. Adding perioperative chemotherapy to surgery can only increase the 5-year overall survival rate by about 5%. There is an urgent need for better systemic treatments. In recent years, immunotherapeutic drugs, represented by PD-1/PD-L1 monoclonal antibodies, have brought breakthroughs from subsequent-line treatment to front-line treatment for NSCLC. Several Phase III studies on perioperative immunotherapy have shown that adding immunotherapy during the neoadjuvant and adjuvant treatment can significantly improve survival outcomes for patients, leading to the development of a new standard treatment for resectable NSCLC. In January 2024, the first PD-1 monoclonal antibodies (Toripalimab) were approved for perioperative treatment of NSCLC in China, starting a new era of perioperative immunotherapy. At present, there is still a lack of unified consensus on the application of perioperative immunotherapy at all levels of medical institutions. In order to privide diagnostic and treatment guidance for clinicians, promote the standardization of clinical practice for immunotherapy in resectable NSCLC, and clarify the controversial opinions regarding perioperative immunotherapy, Lung Cancer Expert Committee of the Chinese Anti-Cancer Association, Chinese Thoracic Oncology Group, Lung Cancer Expert Committee of the Chinese Medical Association Oncology Society jointly published this Consensus and Controversy to provide a guidance for the standardized management of perioperative immunotherapy for NSCLC.

SY13-2 Perioperative immunotherapy for advanced urothelial carcinoma

SY13-2 Perioperative immunotherapy for advanced urothelial carcinoma

What do we know about the role of neoadjuvant targeted therapy in early-stage EGFR-mutant and ALK-fused non-small cell lung cancer?-a narrative review of the current literature.

The standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions is targeted therapy using tyrosine kinase inhibitors (TKIs). However, data are still lacking on the use of TKIs as a neoadjuvant or induction approach. Therefore, this narrative review aims to summarize the current knowledge on resectable EGFR-mutant and ALK-fused NSCLC regarding available perioperative treatment regimens and off-label neoadjuvant use of targeted therapy. The relevant literature was identified by using PubMed and ClinicalTrials.gov (last search phase June 2024) and was restricted to English language. Peer-reviewed manuscripts but also conference abstracts that did not undergo peer-review were included. Patients with EGFR-mutations and ALK-fusions have typically been excluded from available phase III perioperative immunotherapy trials due to lower efficacy and higher toxicity of immunotherapy in those patients. In the adjuvant setting, recent evidence from the phase III ALINA and ADAURA trials demonstrated efficacy and safety of targeted therapy in resected ALK-fused and EGFR-mutant NSCLC. However, to date there is no approval for the use of TKIs as neoadjuvant or induction therapy in those patients. We have therefore identified a number of case series and phase II trials using targeted therapy in resectable EGFR-mutant and ALK-fused NSCLC. Current evidence suggests that targeted therapies might be effective in patients with resectable EGFR-mutant and ALK-positive NSCLC, but ongoing trials will need to provide further evidence on the safety and efficacy of perioperative TKI therapy.

What is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer?

What is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer?

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.

Perioperative immunotherapy for nonsmall cell lung cancer.

Recent years have witnessed significant advancements in the treatment of lung cancer with immunotherapy, primarily centered on immune checkpoint inhibitors (ICIs). Numerous clinical studies have evaluated or are currently evaluating the clinical benefits of neoadjuvant, adjuvant, and perioperative use of ICIs. These findings have notably reshaped the landscape of perioperative treatment for nonsmall cell lung carcinoma (NSCLC). Comparing different treatment modes, adding ICIs in the adjuvant phase to neoadjuvant treatment with ICIs and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. For prognostic factors, ctDNA minimal residual disease (MRD) status might serve as an early predictor of achieving pathological remission. For study endpoints, a positive result with PFS as the primary endpoint may not necessarily translate into overall survival benefits. For perioperative immunotherapy, challenges persist, including the current lack of sensitive and reliable biomarkers, the effect of neoadjuvant therapy on surgical risk as well as the selection of the appropriate study endpoint. In this review, we discuss recent and ongoing trials investigating strategies of neoadjuvant, adjuvant and perioperative immunotherapy in NSCLC, while also proposing considerations for future directions in this continuously evolving field.

Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer

BackgroundNeoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes.MethodsIn this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine–cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine–cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point.ResultsIn total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P=0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group.ConclusionsPerioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.)

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65years compared to those ≥ 65years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65years and male gender may experience greater benefits from perioperative IO-CT.

Perioperative immunotherapy in nonsmall cell lung cancer.

To evaluate and summarize the current clinical efficacy, safety, treatment patterns, and potential biomarkers, to guide future treatment strategies for nonsmall cell lung cancer (NSCLC), improve patient prognosis, and provide a scientific basis for personalized therapy. In recent years, the class of immune checkpoint inhibitors (ICIs), with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors at the helm, has catalyzed groundbreaking advancements within the perioperative treatment milieu for NSCLC. With the positive results of several phase III clinical trials, perioperative immunotherapy has been confirmed to significantly reduce the risk of postoperative recurrence in resectable NSCLC, becoming the new standard for perioperative treatment of stages II to III NSCLC. With the advent of the perioperative immunotherapy era, clinical issues such as the selection of the treatment population, the choice of regimen, the duration of treatment, whether patients with pCR need further adjuvant therapy, and the comprehensive management of patients throughout the perioperative period have attracted widespread attention. The perioperative treatment of NSCLC has fully entered the era of immunotherapy. Multiple clinical studies have confirmed that perioperative immunotherapy can significantly improve the survival benefit of resectable stages II to III NSCLC, establishing a new standard for the perioperative treatment of stages II to III NSCLC.

Improved survival for patients with lung cancer treated with perioperative immunotherapy.

Improved survival for patients with lung cancer treated with perioperative immunotherapy.

Perioperative Immunotherapy for Resectable Non-Small Cell Lung Cancer: Current Evidence and New Standard of Care

Immunotherapy has drastically changed the treatment of lung cancer not only in systemic disease but also in the perioperative setting in locally advanced non-small cell lung cancer. In particular, the neoadjuvant and perioperative therapy regimes of the CheckMate 816 and KEYNOTE-671 studies as well as the adjuvant therapy according to the IMPower010 and the PEARLS/KEYNOTE-091 protocols have already been approved by the European Medicines Agency (EMA) for the treatment of selected cases. Other therapy protocols and combination therapies with varying drug classes and therapy modalities are currently being examined for their effectiveness and tolerance. The new treatment landscape creates new opportunities but also challenges for the treating disciplines. This article will focus on the current evidence for perioperative immunotherapy for resectable lung cancer and the resulting therapy standards, especially with regard to patient selection for both neoadjuvant and adjuvant immunotherapy, as well as current research efforts.

Perioperative immunotherapy in renal cell carcinoma

Perioperative immunotherapy in renal cell carcinoma

Epithelioid pleural mesothelioma successfully treated with perioperative immunotherapy: a case report

BackgroundPleural mesothelioma, characterized by a dismal prognosis even with multimodal therapy, has seen emerging interest in immune checkpoint inhibitors (ICIs) due to their demonstrated efficacy. Here, we present a case of epithelioid-type pleural mesothelioma with chest wall invasion treated with definitive ICI therapy, resulting in a remarkable pretreatment effect.Case presentationA 46-year-old man was diagnosed with an abnormal chest shadow on a medical check, and a computed tomography scan showed pleural thickening at the dorsal right upper chest wall. One of the nodules was suspected to have invaded the chest wall. A needle biopsy revealed epithelioid-type pleural mesothelioma. After five cycles of nivolumab plus ipilimumab, he underwent right pleurectomy/decortication (P/D). Pathological examination revealed a significant treatment effect, showing numerous lymphocytes infiltrating the tumor nodule and viable tumor cells localized at approximately 6 mm.ConclusionAlthough further accumulation of cases is required to evaluate the effectiveness and case selection, P/D after immunotherapy is a useful curative treatment option for advanced pleural mesothelioma.

Clinical outcomes with perioperative nivolumab (NIVO) by nodal status among patients (pts) with stage III resectable NSCLC: Results from the phase 3 CheckMate 77T study.

LBA8007 Background: In CheckMate 77T, perioperative NIVO showed statistically significant EFS improvement vs neoadjuvant (neoadj) chemo followed by adjuvant (adj) placebo (PBO) in pts with stage (stg) II or III resectable NSCLC. We report clinical outcomes by baseline (BL) stg III N2 status, a subgroup with poor historical 5 y survival (26%–36%; Goldstraw J Thorac Oncol 2016). Methods: Adults with resectable stg IIA–IIIB (N2; AJCC v8) NSCLC were randomized to neoadj NIVO 360 mg Q3W + chemo (4 cycles [cyc]) followed by adj NIVO 480 mg Q4W (13 cyc) or neoadj PBO Q3W + chemo (4 cyc) followed by adj PBO Q4W (13 cyc). Primary endpoint: EFS per BICR. Exploratory analysis: efficacy and safety in pts with BL clinical stg III N2 or non N2 disease (dz). Results: BL characteristics were generally similar between pts with stg III N2 (NIVO, 91; PBO, 90) and non N2 dz (55; 57), and between treatment (tx) arms, except a higher percent of pts with N2 dz had NSQ histology and ECOG PS 0 (both arms). Pts with N2 dz had improved EFS with NIVO vs PBO (HR 0.46; 1 y EFS 70% vs 45%) and higher pCR (22.0% vs 5.6%; median f/u 25.4 mo; Table). Pts with non N2 also had EFS benefit with NIVO vs PBO (HR 0.60; 1 y EFS 74% vs 62%) and higher pCR (25.5% vs 5.3%; Table). Surgical feasibility was similar between pts with N2 and non N2 dz and numerically higher with NIVO vs PBO. Of pts with N2 dz, 77% (NIVO) vs 73% (PBO) had definitive surgery (pneumonectomy 1% vs 14%; R0 resection 86% vs 86%); of pts with non N2 dz, 82% vs 79% had definitive surgery (pneumonectomy 13% vs 9%; R0 resection 84% vs 87%). Tumor downstaging postsurgery was seen in most pts with stg III dz and was deeper with NIVO vs PBO: 61% vs 50% (N2; 33% vs 14% to ypT0), 87% vs 76% (non N2; 27% vs 11% to ypT0). Of all pts with stg III dz, nodal downstaging postsurgery was 52% (NIVO) vs 45% (PBO); 46% vs 36% to ypN0. Grade 3–4 TRAEs occurred in 34% (NIVO) and 26% (PBO) of pts with N2; 29% and 21% of pts with non N2 dz. Conclusions: In this exploratory analysis, perioperative NIVO showed clinical benefit vs PBO in pts with stg III NSCLC, regardless of N2 status. Over half of pts with stg III dz had nodal downstaging with NIVO; majority downstaged to ypN0. This first comprehensive analysis by nodal status among pts with stg III dz from a global phase 3 study of perioperative immunotherapy further supports perioperative NIVO as a tx option for pts with resectable NSCLC. Clinical trial information: NCT04025879 . [Table: see text]