Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

Brückl, W.; Ficker, Joachim H.; Zeitler, Gloria

doi:10.1186/s12885-020-07690-8

Cited by 112 publications

(93 citation statements)

References 166 publications

(213 reference statements)

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“…However, a positive KRAS status was significantly associated with worse median PFS in 2nd-line D+R and was also an independent predictor of worse PFS in multivariate Cox regression analysis. To date, there is little evidence on the role of KRAS status in D+R therapy (30). Although KRAS mutations might increase the expression of VEGF, VEGFR1 and VEGFR2 in various tumors including NSCLC, the underlying mechanisms is still unclear (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Brueckl¹,

Reck²,

Rittmeyer³

et al. 2021

Transl Lung Cancer Res

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Background: Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations.However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI.Methods: Retrospective data were collected during routine care from German thoracic oncology centers.Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint.Results: Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis.Conclusions: D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS

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Section: Discussionmentioning

confidence: 99%

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Brueckl¹,

Reck²,

Rittmeyer³

et al. 2021

Transl Lung Cancer Res

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“…Moreover, in first-line and second-line settings, ICI monotherapy and dual therapy or a therapeutic approach in combination with chemotherapy has displayed an overall survival benefit compared to standard platinum-based regimens [23,[27][28][29]. However, not all patients experience favorable response to treatment with ICI due to severe side effects and underlying clinical condition [30]. Although the development of targeted therapy has improved the clinical outcome in a subgroup of lung cancer patients, the five-year survival rate is still less than 20% [2,9,31].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological and Prognostic Significance of Inhibitor of Apoptosis Protein (IAP) Family Members in Lung Cancer: A Meta-Analysis

Fung

Knoefel

Krieg

2021

Cancers

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Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% is non-small-cell and 15% is small-cell lung cancer. The inhibitor of apoptosis proteins (IAPs) represent a heterogeneous family of anti-apoptotic proteins, some members of which have been reported to correlate with clinical outcome in lung cancer. We screened PubMed, Web of Science, and Scopus for studies that investigated the prognostic value and clinicopathological features of IAPs in lung cancer. Forty-five eligible studies with 4428 patients assessed the expression of the IAPs survivin, XIAP, livin, and BRUCE. The pooled hazard ratio (HR) of 33 studies that analyzed overall survival (OS) revealed a positive correlation between survivin expression and poor prognosis. Seven studies displayed a strong association between survivin and disease recurrence. Two studies that assessed the expression of XIAP and livin, respectively, proved a significant relationship of these IAPs with poor OS. Meta-analyses of clinicopathological variables revealed a significant association between survivin and T stage, UICC stage, the presence of lymph node metastasis, and grade of differentiation. In conclusion, high expression of distinct IAPs significantly correlates with prognosis in lung cancer. Therefore, lung cancer patients might benefit from a targeted therapy against specific IAPs.

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“…Gender is a reportedly relevant element that modulates the expression of the PD-1 pathway ( 147 ). In addition, male patients demonstrate a better efficacy of single agent ICIs treatment than their female counterparts ( 147 , 148 ). No studies have illustrated the difference in ICI-related irAEs between men and women ( 146 , 149 ).…”

Section: Contributory Factors Of Ocular Iraes In Lung Cancer Secondary To Icismentioning

confidence: 99%

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

Zhou

Wei

2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.

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Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

Cited by 112 publications

References 166 publications

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV

Clinicopathological and Prognostic Significance of Inhibitor of Apoptosis Protein (IAP) Family Members in Lung Cancer: A Meta-Analysis

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

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