Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

Kurman, Jonathan S.; Murgu, Septimiu

doi:10.21037/jtd.2018.01.79

Cited by 53 publications

(30 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combination treatment modality and clinical unmet needs, being the two major aspects, were ideal resolutions for the development of novel CPIs. To be noticed, challenges to immunotherapy remained to be unsolved including hyperprogression [244,245], immune-related toxicities [246,247], and primary/adaptive resistance to immunotherapy [248]. Moreover, potential novel treatment modalities have aroused great interest and their preliminary performances revealed remarkable prospects for development in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Emerging therapies for non-small cell lung cancer

et al. 2019

View full text Add to dashboard Cite

Recent advances in the field of novel anticancer agents prolong patients' survival and show a promising future. Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although increasing novel anticancer agents were innovated, how to translate and optimize these novel agents into clinical practice remains to be explored. Besides, toxicities and availability of these drugs in specific regions should also be considered during clinical determination. Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Emerging therapies for non-small cell lung cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Progression is defined as an increase in tumour size (which is the summation of the longest diameter of five target lesions) of more than 20% compared to the lowest determined tumour size at any point in time. The possibility of pseudo-progression [4][5][6] necessitated a second update of RECIST and in 2017, iRECIST was adopted as a novel tumour response evaluation tool in patients with immunotherapy treatment [7]. Several authors have suggested that RECIST criteria may be inadequate to capture the response to immunotherapies [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Tumour growth rate as a tool for response evaluation during PD-1 treatment for non-small cell lung cancer: a retrospective analysis

et al. 2019

View full text Add to dashboard Cite

BackgroundImmune checkpoint inhibitors have emerged as a standard of care treatment for non-small cell lung cancer (NSCLC). To get insight into variations in tumour growth kinetics and their potential predictive values for outcome, we evaluated tumour growth rate (TGR) in patients receiving programmed cell death 1 (PD-1) checkpoint inhibitors.Patients and methodsDifferences in TGR before and after the start of treatment were calculated by entering the sum of the longest diameters from computer tomography scans before and after the initiation of therapy into a formula that assumes volumetric exponential tumour growth. TGR variations, possible predictors for TGR changes and its relationship to overall survival (OS) were studied. For comparison, tumour response was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.ResultsAmong the 58 evaluable patients, 37 patients (64%) showed deceleration of TGR and 16 patients (27%) showed an acceleration of TGR after initiation of therapy, with a significant difference in median OS of 18.0 months versus 6.0 months (hazard ratio 0.35, 95% CI 0.18–0.71) between these groups. Four patients (7%) were defined as having hyperprogressive disease. In five patients (9%), tumour growth remained stable. These TGR categories were not significantly different according to age, sex, histology, smoking or previous radiotherapy. Of the patients defined as having progressive disease by RECIST version 1.1 at first follow-up, 40% showed response to checkpoint inhibitors by a decrease in TGR.ConclusionTumour growth kinetics can be used as a clinically relevant predictor for OS in anti-PD-1-treated patients with NSCLC, and may provide additional information to RECIST measurements.

show abstract

“…Moreover, like other therapies, PD-1/PD-L1-targeted antibody therapies may lead to side effects and toxicities, which mainly include immune-related adverse events associated with inflammatory conditions (18) and cardiac toxicity (19). Notably, two atypical responses, i.e., hyperprogressive disease (HPD) and pseudoprogressive disease (PPD) have been observed after the ICT (20,21). This evidence demonstrates that the mechanism underlying ICT targeting PD-1/PD-L1 remains incompletely understood.…”

mentioning

confidence: 99%

Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

Wang

Yang

Zhang

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

168

147

View full text Add to dashboard Cite

The programmed cell death 1 (PD-1) receptor on the surface of immune cells is an immune checkpoint molecule that mediates the immune escape of tumor cells. Consequently, antibodies targeting PD-1 have shown efficacy in enhancing the antitumor activity of T cells in some types of cancers. However, the potential effects of PD-1 on tumor cells remain largely unknown. Here, we show that PD-1 is expressed across a broad range of tumor cells. The silencing of PD-1 or its ligand, PD-1 ligand 1 (PD-L1), promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Conversely, overexpression of PD-1 or PD-L1 inhibits tumor cell proliferation and colony formation. Moreover, blocking antibodies targeting PD-1 or PD-L1 promote tumor growth in cell cultures and xenografts. Mechanistically, the coordination of PD-1 and PD-L1 activates its major downstream signaling pathways including the AKT and ERK1/2 pathways, thus enhancing tumor cell growth. This study demonstrates that PD-1/PD-L1 is a potential tumor suppressor and potentially regulates the response to anti-PD-1/PD-L1 treatments, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.

show abstract

Hyperprogressive disease in patients with non-small cell lung cancer on immunotherapy

Cited by 53 publications

References 17 publications

Emerging therapies for non-small cell lung cancer

Emerging therapies for non-small cell lung cancer

Tumour growth rate as a tool for response evaluation during PD-1 treatment for non-small cell lung cancer: a retrospective analysis

Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

Contact Info

Product

Resources

About