Perioperative Pembrolizumab for Early-Stage Non–Small-Cell Lung Cancer

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 389(6), P. 491 - 503

Published: June 3, 2023

Among patients with resectable early-stage non–small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either alone. Download PDF of the Research Summary. We conducted randomized, double-blind, phase 3 trial to evaluate pembrolizumab in NSCLC. Participants stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned 1:1 ratio receive (200 mg) placebo once every weeks, each which was given cisplatin-based chemotherapy for 4 cycles, followed by surgery weeks up 13 cycles. The dual primary end points event-free survival (the time from randomization first occurrence local progression precluded planned surgery, unresectable tumor, recurrence, death) overall survival. Secondary included major pathological response, complete safety. A total 397 participants group, 400 group. At prespecified interim analysis, median follow-up 25.2 months. Event-free at 24 months 62.4% group 40.6% (hazard progression, death, 0.58; 95% confidence interval [CI], 0.46 0.72; P<0.001). estimated 24-month 80.9% 77.6% (P=0.02, did not meet significance criterion). response occurred 30.2% 11.0% those (difference, 19.2 percentage points; CI, 13.9 24.7; P<0.0001; threshold, P=0.0001), 18.1% 4.0%, respectively 14.2 10.1 18.7; P=0.0001). Across all treatment phases, 44.9% 37.3% had treatment-related adverse events grade higher, including 1.0% 0.8%, respectively, who 5 events. resectable, NSCLC, plus resection significantly improved survival, as compared alone surgery. Overall differ between groups this analysis. (Funded Merck Sharp Dohme; KEYNOTE-671 ClinicalTrials.gov number, NCT03425643.) QUICK TAKE VIDEO SUMMARYNeoadjuvant Pembrolizumab Lung Cancer 02:12

Language: Английский

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Immune-checkpoint inhibition for resectable non-small-cell lung cancer — opportunities and challenges

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(10), P. 664 - 677

Published: July 24, 2023

Language: Английский

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Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(11), P. 2394 - 2411

Published: Sept. 14, 2023

Abstract Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for NSCLC, using major (MPR) as primary endpoint. Eighty-three received a single cycle of treatment: 26 durvalumab (anti–PD-L1) monotherapy, 21 plus oleclumab (anti-CD73), 20 monalizumab (anti-NKG2A), 16 danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher combination arms Safety profiles similar those Multiplatform immune profiling suggested that improved associated enhanced effector infiltration tumors, interferon responses markers tertiary lymphoid structure formation, systemic functional activation. Significance: A can rapidly generate clinical translational data candidate surrogate endpoints like MPR. In NeoCOAST, NSCLC had after or alone tumoral transcriptomic signatures indicative augmented activation function. See related commentary by Cooper Yu, p. 2306. This article is featured Selected Articles from Issue, 2293

Language: Английский

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Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non–Small Cell Lung Cancer

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 29(4), P. 705 - 710

Published: Feb. 15, 2023

Neoadjuvant anti-PD-1 therapy has shown promise for resectable non-small cell lung cancer (NSCLC). We reported the first phase I/II trial of neoadjuvant nivolumab in NSCLC, finding it to be safe and feasible with encouraging major pathological responses (MPR). now present 5-year clinical outcomes from this trial, representing our knowledge, longest follow-up data any type.Two doses (3 mg/kg) were administered 4 weeks before surgery 21 patients Stage I-IIIA NSCLC. recurrence-free survival (RFS), overall (OS), associations MPR PD-L1, evaluated.With a median 63 months, RFS OS rates 60% 80%, respectively. The presence pre-treatment tumor PD-L1 positivity (TPS ≥1%) each trended toward favorable RFS; HR, 0.61 [95% confidence interval (CI), 0.15-2.44] 0.36 (95% CI, 0.07-1.85), At follow-up, 8 9 (89%) alive disease-free. There no cancer-related deaths among MPR. In contrast, 6/11 without experienced relapse, 3 died.Five-year NSCLC compare favorably historical outcomes. improved RFS, though definitive conclusions are limited by cohort size.

Language: Английский

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Neoadjuvant adebrelimab in locally advanced resectable esophageal squamous cell carcinoma: a phase 1b trial

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2068 - 2078

Published: July 24, 2023

Abstract Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here, we reported the results a phase 1b trial PD-L1 blockade with adebrelimab resectable ESCC. Patients received two doses followed by surgery. The primary endpoints were safety and feasibility; secondary included pathologic complete response (pCR) OS. Our data showed feasibility had been met. Common treatment-related adverse events anorexia (32%) fatigue (16%), without grade 3 or more events. Of 30 patients enrolled trial, 25 underwent successful resection surgery delay 24% major responses including pCR rate 8%. 2-year OS was 92%. Responsive an immune-enriched tumor microenvironment phenotype, whereas nonresponsive greater infiltration cancer-associated fibroblasts at baseline. Clonotypic dynamics pre-existing intratumoral T cells hallmark responsive patients. These findings provide rational for anti-PD-L1 monotherapy as therapeutic strategy ClinicalTrials.gov identifier: NCT04215471 .

Language: Английский

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Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(6), P. 1602 - 1611

Published: April 30, 2024

Abstract Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are standard of care most patients metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses improved event-free survival achieved. New antibody combinations may be more efficacious tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive resectable cancer were randomized to receive two preoperative doses nivolumab (anti-PD-1) without relatlimab (anti-LAG-3) therapy. The primary study endpoint was feasibility surgery within 43 days, which met by all patients. Curative resection achieved 95% Secondary endpoints included pathological radiographic response rates, pathologically complete disease-free overall safety. Major (≤10% viable cells) objective 27% 10% (nivolumab) 30% (nivolumab relatlimab) patients, respectively. 100% 90% tumors lymph nodes completely resected. With 12 months median duration follow-up, rates at 89% 93% (nivolumab), relatlimab). Both treatments safe grade ≥3 treatment-emergent adverse events reported 13% per arm. Exploratory analyses provided insights into biological processes triggered immunotherapy. This establishes safety dual PD-1 LAG-3 surgery. ClinicalTrials.gov Indentifier: NCT04205552 .

Language: Английский

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Neoadjuvant and Adjuvant Treatments for Early Stage Resectable NSCLC: Consensus Recommendations From the International Association for the Study of Lung Cancer

Journal of Thoracic Oncology, Journal Year: 2024, Volume and Issue: 19(10), P. 1373 - 1414

Published: June 18, 2024

Language: Английский

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Pulmonary toxicity of immune checkpoint immunotherapy

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(2)

Published: Jan. 15, 2024

Cancer remains a leading cause of mortality on global scale. Lung cancer, specifically non-small cell lung cancer (NSCLC), is prominent contributor to this burden. The management NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), improved patient outcomes. Although generally well tolerated, the administration ICIs can result unique side effects known immune-related adverse events (irAEs). occurrence irAEs involving lungs, inhibitor pneumonitis (CIP), have profound effect both future therapy options and overall survival. Despite CIP being one more common serious irAEs, limited treatment are currently available, part due lack understanding underlying mechanisms involved its development. In Review, we aim provide an overview epidemiology clinical characteristics CIP, followed by examination emerging literature pathobiology condition.

Language: Английский

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Management of locally advanced non‐small cell lung cancer: State of the art and future directions

Cancer Communications, Journal Year: 2023, Volume and Issue: 44(1), P. 23 - 46

Published: Nov. 20, 2023

Abstract Lung cancer is the second most common and deadliest type of worldwide. Clinically, non‐small cell lung (NSCLC) pathological cancer; approximately one‐third affected patients have locally advanced NSCLC (LA‐NSCLC, stage III NSCLC) at diagnosis. Because its heterogeneity, LA‐NSCLC often requires multidisciplinary assessment. Moreover, prognosis much below satisfaction, efficacy traditional therapeutic strategies has reached a plateau. With emergence targeted therapies immunotherapies, as well continuous development novel radiotherapies, we entered an era treatment paradigm for LA‐NSCLC. Here, reviewed landscape relevant modalities, including adjuvant, neoadjuvant, perioperative immune in with resectable with/without oncogenic alterations; combinations chemoradiation immunotherapy/targeted therapy unresectable We addressed unresolved challenges that remain field, examined future directions to optimize clinical management increase cure rate

Language: Английский

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Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives

Journal of Thoracic Oncology, Journal Year: 2023, Volume and Issue: 18(11), P. 1458 - 1477

Published: July 13, 2023

The standard of care (SoC) for medically operable patients with early-stage (stages I–IIIB) NSCLC is surgery combined (neo)adjuvant systemic therapy stages II to IIIB disease and some stage IB or, rarely, chemoradiation (stage III mediastinal lymph node metastases). Despite these treatments, metastatic recurrence common associated poor survival, highlighting the need therapies that are more effective than current SoC. After success targeted (TT) in advanced harboring oncogenic drivers, agents being investigated perioperative (neoadjuvant adjuvant) treatment NSCLC. Adjuvant osimertinib only TT approved use setting, there no neoadjuvant TTs. We discuss importance comprehensive biomarker testing at diagnosis identify individuals who may benefit from treatments review emerging data trials. also address potential challenges establishing TTs as SoC including identification validation early response markers guide accelerate drug development, safety considerations setting. Initial indicate well tolerated EGFR- or ALK-positive Data ongoing trials will determine whether become a new oncogene-addicted resectable

Language: Английский

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