Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Papadopoulos, Vasilis; Maragouli, Elena; Papatsibas, George; Sardeli, Chrysanthi; Man, Yan-Gao; Bai, Chong; Huang, Haidong

doi:10.21037/tlcr.2018.01.04

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…As mentioned, ibrutinib plus nivolumab had an unexpectedly high antitumor activity in GCB DLBCL, emphasizing the clinical benefit of adding nivolumab to ibrutinib. However, overall TMB was lower in responders with GCB DLBCL and in DLBCL patients with PFS >24 versus ≤24 months, contrary to previous reports in non–small-cell lung carcinoma and melanoma linking higher mutational burden with greater effectiveness of immune checkpoint blockade therapy [ 52 , 53 ]. On the other hand, non–small-cell lung carcinoma and melanoma have a very high average mutational burden, unlike the relatively low average mutational burden in DLBCL [54] , suggesting that factors other than TMB may be linked to the antitumoral immune response in DLBCL.…”

Section: Discussioncontrasting

confidence: 71%

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation

Hodkinson

Schäffer

Brody

et al. 2021

Translational Oncology

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Section: Discussioncontrasting

confidence: 71%

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation

Hodkinson

Schäffer

Brody

et al. 2021

Translational Oncology

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“…However, in the nivolumab arm, though OS of patients with high tumor mutation burden (TMB) was low, the ORR and PFS were found to be significantly improved than those in the chemotherapy arm. Therefore, this analysis demonstrated the predictive value of TMB for evaluating the efficacy of immunotherapy in phase-III clinical trial ( Carbone et al., 2017 ; Zarogoulidis et al., 2018 ).…”

Section: First-line Immune-checkpoint Inhibitors Monotherapy For Nsclmentioning

confidence: 81%

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

Huang

Lü

et al. 2020

Front. Pharmacol.

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Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.

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“…From a clinical and basic science perspective, the relationship between tumor mutational burden and response to ICIs is of great interest [19] . It is known that tumors with high mutational burden tend to be immunologically "hot", displaying favorable responses to treatment [20] . Therefore, the specific mechanisms of the DNA damage response (DDR) causing the tumor to be more vulnerable to ICIs represent an active area of research and investigation.…”

Section: Non-small Cell Lung Cancermentioning

confidence: 99%

RANBP9 as potential therapeutic target in non-small cell lung cancer

Tessari

Soliman

Orlacchio

et al. 2020

JCMT

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Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the Western world. Despite progress made with targeted therapies and immune checkpoint inhibitors, the vast majority of patients have to undergo chemotherapy with platinum-based drugs. To increase efficacy and reduce potential side effects, a more comprehensive understanding of the mechanisms of the DNA damage response (DDR) is required. We have shown that overexpressby live cell imaging (Incuyion of the scaffold protein RAN binding protein 9 (RANBP9) is pervasive in NSCLC. More importantly, patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs. Mechanistically, RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated (ATM) kinase signaling. Indeed, the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging (Incuy53 signaling. RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related (ATR) kinase but not to ATM inhibition. The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase (PARP) resulting in a "BRCAness-like" phenotype. In summary, as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo , RANBP9 may be considered as a potential target for the treatment of NSCLC. This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage, particularly in the context of NSCLC. This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.

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Nivolumab as first-line treatment in non-small cell lung cancer patients—key factors: tumor mutation burden and PD-L1 ≥50%

Cited by 10 publications

References 21 publications

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation

First-Line Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Current Landscape and Future Progress

RANBP9 as potential therapeutic target in non-small cell lung cancer

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