Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Дек. 22, 2021

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, Ib arm A) or plus single dose ipilimumab (COMBO, 26, 6 B, 20 IIa) prior to surgery. Primary endpoints feasibility resect no later than week (phase Ib) primary tumor pathological response IIa). is not delayed suspended any patient Ib, meeting the endpoint. Grade 3‒4 immune-related adverse events seen (33%) NIVO MONO 10 26 (38%) total COMBO patients. Pathological response, defined as %-change viable percentage from baseline biopsy on-treatment resection, evaluable 17/20 IIa 29/32 trial (6/6 23/26 COMBO). We observe major (MPR, 90‒100% response) 35% after ICB, both (6/17) whole (8/23), endpoint threshold 10%. MONO's MPR rate 17% (1/6). None develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based lesion glycolysis identifies A AID/APOBEC-associated mutational profile an decrease hypoxia RNA signature observed Our data indicate that neoadjuvant ICB feasible encouragingly efficacious HNSCC.

Язык: Английский

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Neoadjuvant immunotherapy for non–small cell lung cancer: State of the art

Cancer Communications, Год журнала: 2021, Номер 41(4), С. 287 - 302

Опубликована: Март 10, 2021

Abstract Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy immunotherapy. Immune checkpoint inhibitors (ICIs) have rapidly evolved from investigational drugs standard of care for treatment metastatic non‐small cell lung (NSCLC). In particular, antibodies that block inhibitory immune checkpoints, such as programmed death protein 1 (PD‐1) ligand (PD‐L1), revolutionized advanced NSCLC, when administered alone or combination with chemotherapy. Immunotherapy is associated higher response rates, improved overall survival (OS), increased tolerability compared conventional cytotoxic These benefits may increase utility immunotherapy its combinational use chemotherapy neoadjuvant patients NSCLC. Early findings various ongoing clinical trials suggest ICIs combined significantly reduce systemic recurrence improve long‐term OS cure rates resectable Here we further summarize safety efficacy regimens including elaborate role addition, discuss several unresolved challenges, evaluations assess response, adjuvant after immunotherapy, oncogenic‐addicted tumors, predictive biomarkers. We also provide our perspective on ways overcome current obstacles establish a care.

Язык: Английский

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Sintilimab: A Promising Anti-Tumor PD-1 Antibody

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Ноя. 26, 2020

Sintilimab (Tyvyt

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Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer

OncoImmunology, Год журнала: 2021, Номер 10(1)

Опубликована: Янв. 1, 2021

Multimodality treatment provides modest survival benefits for patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC). Nevertheless, preoperative immunotherapy has continuously been shown to be promising in treating resectable NSCLC.This phase 2 trial enrolled AJCC-defined stage IIIA or T3-4N2 IIIB NSCLC deemed surgically resectable. Patients received three cycles of neoadjuvant intravenous PD-1 inhibitor toripalimab (240 mg), carboplatin (area under the curve 5), and pemetrexed (500 mg/m2 adenocarcinoma) nab-paclitaxel (260 other subtypes) on day 1 each 21-day cycle. Surgical resection was performed 4–5 weeks afterward. The primary endpoint major pathological response (MPR), defined as less than 10% residual tumor remaining at time surgery.Thirty-three were enrolled, whom 13 (39.4%) had disease. Thirty (90.9%) underwent all except one (96.7%) achieved R0 resection. Twenty (60.6%) intention-to-treat population an MPR, including 15 (45.5%) who a complete (pCR). MPR pCR rates per-protocol 66.7% 50.0%, respectively. surgical complications included cases arrhythmias, case prolonged air leak, chylothorax. most common grade 3 treatment-related adverse event (TRAE) anemia (2, [6.1%]). Severe TRAEs (3.0%) peripheral neuropathy that resulted cancellation.Toripalimab plus platinum-based doublet chemotherapy yields high rate, manageable toxicity, feasible III NSCLC.Trial ClinicalTrials.gov (NCT04304248)

Язык: Английский

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Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer

Translational Lung Cancer Research, Год журнала: 2020, Номер 9(6), С. 2696 - 2715

Опубликована: Дек. 1, 2020

Lung cancer is the leading cause of cancer-related death worldwide and in China (1). According to statistics National Cancer Center China, there were 733,300 new cases non-small cell lung (NSCLC) approximately 610,200 related deaths 2015 (2). For patients with early staged disease, surgery mainstay treatment, it commonly followed by adjuvant chemotherapy for locally advanced resectable NSCLC. Although complete surgical resection may be curative NSCLC, 25–70% (with different proportion according stage) eventually relapse despite (3). Platinum-based has been shown marginally increase 5-year survival rate 4–8% (4-6). Even after treatment indicated therapies eligible cases, 20–30% stage I, 50% II, 60% IIIA still die within 5 years (7). In past decade, experts have conducted a number investigations on perioperative management NSCLC; however, progress remains slow, high risk recurrence death. Neoadjuvant therapy defined as any delivered prior definitive local intended cure rate. It provides several theoretical benefits managing such setting of, neoadjuvant given radical this approach can also goals downstaging, improving rate, more promptly treating subclinical micro-metastases than approaches, therapy. addition, compliance better setting, biological effect analyzed directly resected tumor specimens (8). A meta-analysis IB‒IIIA NSCLC that compared plus subsequent vs. alone showed was 5% higher receiving (NCT) (9). Therefore, comprehensive data suggest that, NCT improves but appear show no significant benefit (10). In last years, immune checkpoint inhibitors (ICIs) profoundly changed paradigm (11-15). Immunotherapy provided hope long-term minority metastatic cancer. treatment-naive driver mutation-negative single agent pembrolizumab 23.2%; previously treated rates nivolumab 15.5% 16%, respectively (16,17). Given profound impact made immunotherapy drugs attention directed recent toward investigating potential role early-stage patients, whether they, too, achieve from inclusion into their algorithms. Many phase Ib/II clinical trials reported promising results, series large-scale III are underway. However, these various employed strategies immunotherapy, terms specific regimens well cycles (18). To guide Chinese thoracic surgeons well-known participated an in-depth discussion hot topics controversial issues formed Expert consensus non-small-cell incorporating latest evidence immunotherapy.

Язык: Английский

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Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience

Lung Cancer, Год журнала: 2021, Номер 153, С. 150 - 157

Опубликована: Янв. 22, 2021

Язык: Английский

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Efficacy, Safety, and Biomarker Analysis of Neoadjuvant Camrelizumab and Apatinib in Patients With Resectable NSCLC: A Phase 2 Clinical Trial

Journal of Thoracic Oncology, Год журнала: 2023, Номер 18(6), С. 780 - 791

Опубликована: Март 2, 2023

Язык: Английский

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Does major pathological response after neoadjuvant Immunotherapy in resectable nonsmall-cell lung cancers predict prognosis? A systematic review and meta-analysis

International Journal of Surgery, Год журнала: 2023, Номер unknown

Опубликована: Май 29, 2023

Overall survival is the gold-standard outcome measure for phase 3 trials, but need a long follow-up period can delay translation of potentially effective treatment to clinical practice. The validity major pathological response (MPR) as surrogate non small cell lung cancer (NSCLC) after neoadjuvant immunotherapy remains unclear.

Язык: Английский

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Non-small cell lung cancer: Emerging molecular targeted and immunotherapeutic agents

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2021, Номер 1876(2), С. 188636 - 188636

Опубликована: Окт. 15, 2021

Язык: Английский

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Neoadjuvant immunotherapy for advanced, resectable non–small cell lung cancer: A systematic review and meta‐analysis

Cancer, Год журнала: 2023, Номер 129(13), С. 1969 - 1985

Опубликована: Март 30, 2023

Abstract Background Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non‐small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD‐guided systematic review and meta‐analysis were (1) to assess the safety efficacy nIT, (2) compare neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), (3) explore predictors pathologic response with nIT their association outcomes. Methods Eligibility was stage I–III NSCLC receipt programmed death‐1/programmed death ligand‐1 (PD‐L1)/cytotoxic T‐lymphocyte–associated antigen‐4 inhibitors before resection; other forms modalities and/or adjuvant therapies allowed. For statistical analysis, Mantel–Haenszel fixed‐effect or random‐effect model used, depending on heterogeneity (I 2 ). Results Sixty‐six articles met criteria (eight randomized studies, 39 prospective nonrandomized 19 retrospective studies). pooled complete (pCR) rate 28.1%. estimated grade ≥3 toxicity 18.0%. Compared nCT, nCIT achieved higher rates pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p < .001), progression‐free survival (PFS) (hazard [HR] 0.51; CI, 0.38–0.67; overall (OS) (HR, 0.36–0.74; = .0003) but yielded similar (OR, 1.01; 0.67–1.52; .97). results remained robust sensitivity analysis when all publications removed. associated improved PFS 0.25; 0.15–0.43; .001) OS 0.26; 0.10–0.67; .005). PD‐L1 expressors (≥1%) more likely achieve 2.93; 1.22–7.03; .02). Conclusions In patients NSCLC, safe efficacious. PFS/OS over particularly in who had tumors that expressed PD‐L1, without increasing toxicities. Plain Language Summary This 66 studies showed alone, survival, ligand‐1,

Язык: Английский

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