Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC

Cancer Immunology Research, Год журнала: 2017, Номер 5(5), С. 417 - 424

Опубликована: Апрель 15, 2017

Abstract We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated anti-PD-1 antibody, pembrolizumab. The discovery cohort was drawn from phase I Keynote 001 trial, whereas validation 002, 006, EAP trials non–small cell (NSCLC) 001. Liver metastasis associated reduced shortened progression-free survival [PFS; objective rate (ORR), 30.6%; median PFS, 5.1 months] compared without (ORR, 56.3%; 20.1 months) P ≤ 0.0001, confirmed (P = 0.0006). presence of significantly increased likelihood progression (OR, 1.852; < 0.0001). In a subset biopsied (n 62), density at invasive margin (liver metastasis+ group, n 547 ± 164.8; metastasis− 1,441 250.7; 0.016). A PFS also observed NSCLC [median 1.8 months; 95% confidence interval (CI), 1.4–2.0], those 119, 4.0 CI, 2.1–5.1), 0.0094. Thus, metastatic that had been pembrolizumab were responses metastases marginal infiltration, providing potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417–24. ©2017 AACR.

Язык: Английский

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Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis

BMJ, Год журнала: 2018, Номер unknown, С. k3529 - k3529

Опубликована: Сен. 10, 2018

Abstract Objective To evaluate the relative efficacy of programmed cell death 1 (PD-1) or ligand (PD-L1) inhibitors versus conventional drugs in patients with cancer that were PD-L1 positive and negative. Design Meta-analysis randomised controlled trials. Data sources PubMed, Embase, Cochrane database, conference abstracts presented at American Society Clinical Oncology European Medical up to March 2018. Review methods Studies PD-1 (avelumab, atezolizumab, durvalumab, nivolumab, pembrolizumab) had available hazard ratios for based on positivity negativity included. The threshold was stained accounted 1% tumour cells, immune assayed by immunohistochemistry staining methods. Results 4174 advanced metastatic cancers from eight trials included this study. Compared agents, associated significantly prolonged overall survival both (n=2254, ratio 0.66, 95% confidence interval 0.59 0.74) negative (1920, 0.80, 0.71 0.90). However, efficacies blockade treatment different (P=0.02 interaction). Additionally, negative, long term clinical benefits observed consistently across interventional agent, histotype, method randomisation stratification, type immunohistochemical scoring system, drug target, control group, median follow-up time. Conclusions therapy is a preferable option over are This finding suggests expression status alone insufficient determining which should be offered therapy.

Язык: Английский

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Cancer Neoantigens

Annual Review of Immunology, Год журнала: 2018, Номер 37(1), С. 173 - 200

Опубликована: Дек. 14, 2018

Malignant transformation of cells depends on accumulation DNA damage. Over the past years we have learned that T cell-based immune system frequently responds to neoantigens arise as a consequence this Furthermore, recognition appears an important driver clinical activity both cell checkpoint blockade and adoptive therapy cancer immunotherapies. Here review evidence for relevance in tumor control biological properties these antigens. We discuss recent technological advances utilized identify neoantigens, recognize them, individual patients. Finally, strategies can be employed exploit interventions.

Язык: Английский

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Tumor Immunology and Tumor Evolution: Intertwined Histories

Immunity, Год журнала: 2020, Номер 52(1), С. 55 - 81

Опубликована: Янв. 1, 2020

Язык: Английский

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Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC

Nature Reviews Clinical Oncology, Год журнала: 2019, Номер 16(6), С. 341 - 355

Опубликована: Фев. 4, 2019

Язык: Английский

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